A formula containing L-arginine (lysylated), calcium, magnesium, and zinc, which supports linear growth and development.

Abstract

Composition comprising a mineral combination: calcium, magnesium, zinc; an amino acid combination: L-lysine, L-tryptophan or other amino acids; a vitamin combination: vitamin D3, vitamin K2, vitamin A; a bioactive peptide combination: casein phosphopeptide, collagen tripeptides, egg yolk tripeptides / hydrolyzed egg yolk flour.

Description

Technical field

[0001] The invention relates to a composition based on an amino acid complex, wherein L-arginine is the primary component, together with a mineral and vitamin composition comprising calcium, magnesium, zinc, vitamin A, vitamin D3, and vitamin K2 as major components, as well as other active ingredients. By improving mineral absorption and targeted deposition, providing substrates for bone matrix synthesis, and promoting active longitudinal growth of the growth plate complex, it supports the longitudinal development of the skeleton and improves growth and developmental parameters. This composition is intended to support the linear growth of children and adolescents. Background technology

[0002] Human growth and development proceed through three central phases: ① Infancy and early childhood, 0-3 years, a rapid growth window and the first peak of growth; ② School age, approximately 4-10 years, a stable growth phase; ③ Pre- and post-puberty: approximately 8-13 years for girls and approximately 9-14 years for boys, the second and final peak of growth.

[0003] General principles of child growth and development: ① A continuous process from quantitative to qualitative changes: Child growth and development is a complex process that includes not only increases in height and weight, but also the differentiation of organs and the gradual maturation of functions. ② Phased nature: Each growth and development phase is unique; a disability in one phase can affect the subsequent phase. ③ Growth and development rate is cyclical: Using height and weight as an example, there are two accelerations in growth from infancy to maturity, namely during infancy and the pubertal development phase.

[0004] In the first year of life, body length can increase by approximately 25 cm, and in the second year by approximately 10-12 cm. Afterward, growth stabilizes during school age, with an annual increase of approximately 5-7 cm. Following the onset of puberty, there is a growth spurt: in girls, the maximum annual growth rate is typically around 8-9 cm per year, and in boys up to 9-10 cm per year. The timing of this peak growth is closely correlated with pubertal development. The growth spurt occurs earlier in girls than in boys, and puberty also begins 2-3 years earlier in girls. Boys exhibit a faster growth rate, and their final height exceeds that of girls.

[0005] The most noticeable changes during puberty are the significant increase in height and weight, and the associated increased need for calcium; adequate calcium intake is particularly important during linear growth. Precocious maturation affects growth potential, as it prematurely activates the final major growth spurt. Sex hormones stimulate the active growth of the growth plate and simultaneously accelerate its maturation and closure.

[0006] The most noticeable changes of puberty involve the development of secondary sexual characteristics and endocrine alterations. Activation of the gonadotropic axis (hypothalamus-pituitary-gonads, HPG axis) leads to elevated estrogen / testosterone levels, which not only drive the development of secondary sexual characteristics but also promote the secretion and sensitivity of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). IGF-1 promotes the proliferation and maturation of cartilage cells and indirectly influences linear growth and bone maturation. The GH-IGF-1 axis exhibits pulsatile increases in the evening during deep sleep, which are closely related to regular sleep and nutritional status.

[0007] If the pituitary gland partially or completely fails to synthesize or secrete growth hormone, or if the structure of the GH molecule is abnormal, this can lead to a growth and developmental disorder—growth hormone deficiency, or GHD. GHD typically manifests as delayed bone maturation by two years or more, reduced mobility, and loss of appetite.

[0008] During puberty, organ and body systems mature gradually, including the continued mineralization of the skeletal system and longitudinal growth; the growth and development processes exhibit characteristics of "key phases" and "sensitive phases": external factors such as nutrition, exercise, sleep and disease burden have a particularly strong influence on final size and peak bone mass within certain time windows.

[0009] The linear growth phase occurs primarily through the epiphyseal plate (growth plate) of the long bones. The epiphysis is located between the skull (diaphysis) or trunk and the epiphysis, consists of hyaline cartilage, and exhibits distinct columnar structures as well as functional zones. The epiphyseal plate is divided into structural and functional zones as follows: • Resting zone (residual zone): Cartilage cells are in a low proliferation state; they serve as a cellular reserve and signaling hub. Reserve chondrocytes and nutrients provide the cell source and support for the proliferation zone. • Proliferation zone: Cartilage cells divide rapidly and arrange themselves longitudinally in columns, thereby driving the longitudinal growth of the skeleton; it determines the “speed” of longitudinal growth. • Hypertrophic zone: Cartilage cells increase in volume, the matrix changes, calcification occurs, vessels and osteoblasts penetrate and replace the cartilage tissue locally, enabling endochondral ossification. • Calcification zone: In this area, the calcification of the cartilage matrix begins; cartilage cells gradually die off. • Ossification zone: Osteoblasts replace the dead cartilage cells, deposit new bone matrix and form schizoid bone structures.

[0010] Longitudinal growth occurs through the proliferation of cartilage cells in the epiphyseal plate and through endochondral ossification within the cartilage. The proliferation zone is the key area during accelerated bone growth and is highly sensitive to growth factors (such as growth hormone GH and IGF-1), which promote the proliferation and activity of cartilage cells.

[0011] Key signaling networks controlling cartilage cell proliferation and differentiation, as well as bone formation, include IHH / PTHrP feedback loops, FGF / FGFR3, Wnt / β-catenin, BMP, Runx2 / Osx, and other pathways. Local growth factors (such as IGF-1) promote cartilage cell proliferation and hypertrophy and regulate collagen and proteoglycan synthesis. Mineralization of the hypertrophic zone of the cartilage matrix and vascular infiltration lead to the deposition of type I collagen by osteoblasts, resulting in mineralized bone structures. This progressively supports longitudinal growth and increases bone density.

[0012] Coordination of the GH-IGF-1 axis with sex hormones: GH is secreted by the pituitary gland and, together with IGF-1 produced by the liver and local tissues, acts on the epiphyseal plate and bone tissue. IGF-1 stimulates the proliferation and hypertrophy of cartilage cells and enhances the synthetic capacity of osteoblasts for bone matrix. The rise in sex hormones during puberty increases the peaks in GH secretion; furthermore, estrogen and testosterone promote the maturation and final closure of the epiphyseal plate. Delayed puberty or inadequate nutrition can therefore shorten the growth peak and affect final height as well as the quality of peak bone mass.

[0013] Closure of the epiphyseal plate and cessation of linear growth: Once estrogen reaches a certain threshold, the epiphyseal plate ossifies and closes, thus terminating linear growth. Diet, endocrine disorders, and chronic diseases can modify this process.

[0014] Nutrition is also crucial during linear skeletal growth: key nutrients and minerals influence bone development; the bone matrix consists predominantly of type I collagen, and minerals dominate as hydroxyapatite crystals (which provide hardness). The intake and availability of calcium and phosphate, the regulatory role of magnesium, the effects of vitamin D and vitamin K on the mineralization and carboxylation of bone matrix proteins, the support provided by zinc in synthesis processes and enzyme systems, and the supply of essential amino acids for collagen and cartilage matrix proteins all jointly determine longitudinal growth and the quality of bone mineralization.

[0015] Growth charts for height and weight (Z-scores or percentiles) published by authorized institutions such as the WHO or the CDC serve as common tools for monitoring individual developmental variations as well as malnutrition / overweight. Overall, evidence shows that adequate protein intake and micronutrients, sufficient vitamin D status, regular exercise with exertion, healthy sleep, and a low disease burden are fundamental conditions for supporting the growth and development of children and adolescents.

[0016] Malnutrition can be divided into energy / protein deficiency and micronutrient deficiency. It affects growth plates, bone mineralization, immunity, and cognitive function, and is particularly significant during critical developmental phases. Studies show lower growth hormone levels in malnourished children.

[0017] Protein and essential amino acid deficiencies: Deficits in total protein and essential amino acids lower IGF-1 levels, inhibit cartilage cell proliferation / hypertrophy, and lead to growth stunting. Research suggests that adequate protein intake in age-appropriate children correlates positively with serum IGF-1; a low-protein diet lowers IGF-1 and impairs indicators of bone formation. Lysine is one of the essential limiting amino acids and is associated with protein synthesis, collagen cross-linking in bone tissue, and calcium absorption. Lysine deficiency is linked to delayed growth and impaired immune function.

[0018] Calcium and vitamin D deficiency: Insufficient calcium intake directly restricts bone mineralization, leading to low bone density, bone pain, and an increased risk of fractures. Vitamin D deficiency (low 25(OH)D levels) causes reduced calcium and phosphate absorption and secondary hyperparathyroidism, affecting epiphyseal cartilage calcification and bone formation. Deficiency in childhood can cause rickets; in adolescence, it affects the development of maximum skeletal bone mass. Several randomized controlled trials and meta-analyses suggest that in populations with low calcium or vitamin D status, supplementation improves bone density indicators and reduces fracture risk.

[0019] Zinc, magnesium, and vitamin K deficiencies: Zinc is involved in DNA / RNA synthesis and the function of numerous enzymes; zinc deficiency is associated with delayed linear growth and impaired immune function. Zinc supplementation can increase linear growth rates in deficient populations. Magnesium acts as a cofactor in thousands of enzyme reactions and influences bone matrix formation as well as the metabolism of PTH and vitamin D; hypomagnesemia is associated with insufficient skeletal mineralization and loss of muscle function. Vitamin K (especially vitamin K2 in forms such as menaquinone-7) is necessary for the gamma-carboxylation of osteocalcin (OCN) and matrix Gla protein (MGP); insufficient carboxylation can reduce mineralization quality and affect the balance between cartilage and vascular calcium.

[0020] WHO and UNICEF reports show that chronic malnutrition and micronutrient deficiencies are significantly correlated with growth retardation in preschool and school-age children. Systematic reviews suggest that in low-intake populations, calcium / vitamin D / zinc supplementation has positive effects on bone mineral density and height gain; improvements in protein quality and essential amino acid intake increase serum IGF-1 and accelerate linear growth. Conversely, persistent deficiencies lead to reduced peak skeletal height, increased risk of osteoporosis and fractures in adulthood; cumulative bone mass in childhood / adolescence determines roughly 60–80% of later bone health. Practical new product

[0021] The fundamental objective of the present invention is to provide a nutrient composition that enables effective therapy for improving the growth and linear skeletal development of children and adolescents. This objective is achieved by the embodiments described in the claims.

[0022] Accordingly, the invention comprises a core composition based on L-arginine and calcium / magnesium / zinc, which includes L-arginine, glutamine, tryptophan, and other amino acids such as L-arginine, as well as zinc and minerals such as calcium, magnesium, etc., vitamin D3, vitamin K2, collagen tripeptides, yolk protein peptides, casein phosphopeptide, and other active peptide components. By increasing the uptake of essential amino acids, a relatively intensive growth state and an optimal growth rhythm are maintained, thereby stimulating the active growth of the epiphyseal plate to support longitudinal skeletal growth. Simultaneously, mineral uptake is increased and targeted deposition is enabled to provide substrates for bone matrix synthesis and thus promote skeletal length strength.

[0023] CN101268835B refers to a high-calcium particle product whose calcium source is enzymatically digested bone meal, combined with Poria cumaris extract, whole milk powder, oligosaccharides, casein phosphopeptide, dried egg yolk, taurine, vitamin C, vitamin A, vitamin B1, vitamin B2, vitamin B6, iron, zinc, iodine, and manganese. The formulation provides a variety of nutrients for growth and development, promotes calcium absorption, supports bone development, prevents calcium deficiency in children, and may also support intellectual development.

[0024] JP3708115B2 describes a mixed calcium and vitamin D supplement; nutrient and mineral additives include calcium citrate malate and vitamin D. Estrogen may also be used with these supplements. These supplements provide at least 25% of the recommended daily allowance (RDA). Calcium with vitamin D can be taken in addition to a normal diet. Such supplements are intended to increase bone growth and contribute to the treatment of age-related bone loss in humans and animals.

[0025] RU2501553C2 relates to a patented composition designed to promote the normal development and growth of infants and young children while being more digestible than conventional formulations. The core of the composition is the provision of carbohydrate-like molecules that act as a pro- or prebiotic source and provide "extra calcium." Calcium gluconate is preferably used to improve the intestinal environment, reduce the formulation's burden, and promote a softer, more digestible stomach while maintaining the bioavailability of calcium. Additionally, the formulation contains lipids / fats, protein sources, long-chain polyunsaturated fatty acids with DHA (in a specific ratio to ARA), optionally TGF-β, and probiotics / prebiotics to coordinate oral tolerability and intestinal health.

[0026] US6106874A: A patent application proposing a fruit juice-based nutritional beverage with clarification, no sedimentation, no stabilizer, low viscosity, and low pH (pH 3.0 to 4.0), and describing a manufacturing process for it. The core of the process involves using unetched and clarified fruit juices as a matrix, combined with a highly bioavailable calcium source, natural milk minerals, or calcium gluconate from milk juice or mixtures thereof. By eliminating conventional stabilizers (pectin, gelling agents, fats), a high calcium concentration is achieved while maintaining clarity and a light consistency; optionally, whey protein isolates, as well as various water-soluble vitamins and iron, can be added without compromising physical stability or sensory properties.The invention solves the problems of previous calcium-enriched fruit juices such as sedimentation, browning, thickening and unsatisfactory mouthfeel and offers a refreshing alternative especially for children, women (breastfeeding, postmenopausal) and patients with milk base preparation refusal.

[0027] The market for growth-promoting or calcium supplementation products for children and adolescents is predominantly based on individual minerals or vitamins, typically calcium in combination with vitamin D3. A holistic approach to absorption, transport, directed deposition, and matrix synthesis that integrates magnesium, zinc, and vitamin K2 is lacking, resulting in a calcium / magnesium imbalance, insufficient calcium absorption, and limited bone deposition. Furthermore, the mineral content is often too low to fully meet the needs of children during their rapid growth phase; for example, gummies or capsules typically contain 100-200 mg of calcium and 0-50 mg of magnesium per unit. The daily requirement for calcium for children and adolescents aged 7-18 years is 800-1000 mg, and for magnesium, 200-330 mg / day.Different dosage forms influence absorption; available forms include tablets, chewable minerals, soft capsules, gummies, liquid preparations, and powders / granules. Liquid preparations are generally considered to have the highest absorption rate because calcium does not need to disintegrate and is more readily available to the intestine; they also have the largest mucosal surface area in contact with the body. The present invention provides a liquid dosage form that maximizes the bioavailability of the active ingredients. Furthermore, its improved palatability compared to tablets and capsules significantly enhances long-term usability in children.

[0028] Compared to liquid preparations with a relatively high mineral content, this formulation offers additional amino acids and active peptide components, tailored to the nutritional needs of children and adolescents and the mechanisms of skeletal longitudinal growth, thereby achieving more targeted support for linear growth. The combined use of L-lysine and calcium acts synergistically; this relationship is medically utilized in the treatment of childhood bone dysplasia, and the effect surpasses that of a single-ingredient preparation. The introduction of collagen tripeptides and eggshell peptides enables targeted stimulation of the active growth plate of cartilage cells, thereby promoting longitudinal skeletal growth—a key aspect of linear growth.

[0029] Individual purposes and functions of the individual components: L-Lysine: L-Lysine is an essential amino acid that the body cannot synthesize and must obtain from food. It is directly involved in all protein synthesis and determines the optimization of tissue growth and repair. Lysine plays a vital role in development and growth. It serves as a precursor for maintaining a healthy nitrogen balance in the body. Furthermore, lysine reduces urinary calcium concentration, increases calcium absorption, and strengthens bones; it stimulates osteoblast activity and thus promotes overall bone health. In malnourished children, lysine often acts as a limiting amino acid. Studies have shown that lysine supplementation can help support children's growth and development.

[0030] Reasons for a combined intake of lysine and calcium include: Lysine promotes the absorption and dissociation of calcium. Since calcium from food sources and calcium supplements is usually present in the form of calcium compounds, it must first be dissociated in the stomach by gastric acid to be available as free calcium and absorbed in the small intestine. This leads to insufficient calcium supplementation, particularly in infants, young children, and the elderly with reduced gastric acid secretion. Lysine promotes the secretion of gastric acid, effectively improving the bioavailability of this pharmacokinetic process and increasing both the dissociation of calcium salts and the excretion of calcium from food. • Lysine increases the intestinal absorption of calcium, especially in the absence of a vitamin D deficiency; this effect is due to lysine increasing the intestinal NO concentration. • A third effect of lysine is the promotion of the formation of bone collagen fibers. Lysine serves as a building block of bone collagen fibers, exists in the form of hydroxylysine and glycosylhydroxylysine in collagen fibers, and thus contributes to the stabilization of the triple helix structure; in this way, lysine indirectly participates in bone calcification.

[0031] Lysine in skeletal calcification: Collagen comprises approximately 90% of the bone matrix. The primary function of collagen is to induce mineralization. Collagen cross-linking occurs after the enzymatic conversion of lysine or hydroxylysine residues to aldehyde groups within the peptide bonds. Lysine plays a key role in this process. It participates in the synthesis of type I collagen and in stabilizing the triple helix, providing the ordered organic framework necessary for mineralization. Hydroxyapatite preferentially nucleates in areas containing collagen fibers; in cases of insufficient collagen or disrupted arrangement, directed deposition of calcium phosphate is difficult, impairing mineralization efficiency and bone quality. In bone, the calcium content increases while the number of lysine residues decreases, indicating a more mature, highly cross-linked, and fully mineralized collagen matrix.During bone calcification, lysine / hydroxylysine residues are oxidized to aldehyde forms by lysine oxidase (LOX) and converted into stable cross-links; with increasing cross-linking, the amount of free lysine or hydroxylysine residues after hydrolysis decreases. Simultaneously, a mature and ordered collagen matrix supports the directed deposition of hydroxyapatite, leading to increased calcium content in the bone. Consequently, there is a negative correlation between free lysine residues and matrix maturity; a low lysine residue content tends to reflect increased matrix maturity and mineralization. Therefore, lysine status is a key factor in collagen fiber formation; collagen forms the framework of the skeleton and influences mineralization as well as bone growth and development.

[0032] Tryptophan: Tryptophan is an essential amino acid and a precursor to neurotransmitters. Tryptophan can cross the blood-brain barrier and be converted to 5-hydroxytryptamine (5-HT), which further contributes to melatonin synthesis, thus forming a neuroendocrine axis of tryptophan → 5-HT → melatonin. This axis is closely linked to the sleep-wake cycle; deep, restorative sleep increases nocturnal growth hormone (GH) pulses and, via the IGF-1 pathway, supports the proliferation and hypertrophy of cartilage cells in the growth plate, as well as the synthesis of collagen and matrix proteins and bone mineralization to support linear growth. In practical terms, this means that during the day, tryptophan-dependent conversions to 5-HT in sufficient light contribute to a more stable state of wakefulness and improved mood; at night, 5-HT is converted to melatonin in the dark, which facilitates falling asleep.By optimizing sleep and emotional pathways, nocturnal GH pulse formation and growth plate activity are indirectly supported, thus creating a more stable growth-relevant endocrine environment.

[0033] Calcium: As a key mineral for hydroxyapatite, calcium supports bone mineralization and skeletal strength; calcium is actively absorbed through the intestinal mucosa under the guidance of vitamin D. In conjunction with vitamin K2, it enables targeted deposition and efficient utilization of calcium in bone.

[0034] Calcium supplements are commonly available in the form of calcium carbonate, calcium citrate, and calcium gluconate. Calcium carbonate is high in calcium and low in cost; it should be taken with meals to improve absorption. It can irritate the stomach and is suitable for people with normal stomach acid production. Calcium citrate has a higher absorption rate, requires less stomach acid, and can be taken on an empty stomach. Calcium gluconate and calcium lactate are well tolerated, but their absorption tends to be lower than that of calcium citrate.

[0035] Magnesium: As a cofactor of numerous enzymes, it participates in the secretion of parathyroid hormone and the activation of vitamin D, and supports bone metabolism and neuromuscular function. Together with calcium and vitamin D3, it forms an absorption and homeostasis regulatory axis, increasing the availability of mineralization precursors and bone remodeling efficiency. Magnesium deficiencies impair bone growth, reduce the number of osteoblasts, increase osteoclast activity, and lead to a loss of trabecular structures; they also stimulate cytokine activity in bone.

[0036] Zinc: The physiological effects of zinc in mineral supplements or dietary supplements containing calcium, magnesium, and other minerals primarily consist of promoting bone growth and metabolism, immune function, and cell division. In particular, zinc is involved in the synthesis of the bone matrix, the regulation of osteogenesis and osteoclast balance, promotes protein and DNA synthesis, supports cell proliferation and differentiation, and also plays an important role in immune responses, antioxidant protection, and wound healing.

[0037] Vitamin D3: The central function of vitamin D3 is to increase the absorption of calcium and phosphate in the intestine by upregulating TRPV6 and calcium binders, thus maintaining blood calcium homeostasis. It acts in a coordinating role in combination with vitamin K2, creating an "absorption-absorption-depot" synergy: Vitamin D3 first increases the absorption of calcium into the body, while vitamin K2 directs its deposition in the bones. Magnesium acts as a necessary cofactor for the activation and signaling pathways of vitamin D.

[0038] Vitamin K2: Mediates the gamma-carboxylation of osteocalcin (OCN) and matrix Gla protein (MGP), promotes directed calcium deposition in bone, and maintains the mineralization balance between cartilage and blood vessels. It acts synergistically with vitamin D3 and calcium to establish a "directed deposition technique," increasing the efficiency of mineral utilization and reducing the risk of extracorporeal calcium deposits.

[0039] Vitamin A: Plays a regulatory role in bone metabolism; vitamin A participates in osteoblast activity and the regulation of bone remodeling, supports bone formation and inhibits excessive osteoclast activity, and contributes to improved bone mass and structural development. Use within the safe dosage range is necessary to maintain the balance of bone metabolism. In growth plate and cartilage differentiation, it participates in the differentiation and maturation of cartilage cells and supports the intracartilaginous ossification process as well as the orderly development of the epiphyseal plate.

[0040] Collagen tripeptides: Collagen tripeptides are smaller fragments of collagen, about one-fifth the molecular size of conventional collagen, and consist of three amino acids. They play two main roles in growth: First, they activate osteogenesis signals, increasing IGF-1 concentrations. IGF-1 is considered longitudinal growth factor, a metabolite of growth hormone, and its concentration in growth plate cartilage cells is highly sensitive. An increase in IGF-1 enhances the proliferation and activity of cartilage cells. Cartilage cell activity is further increased by the activity of alkaline phosphatase, which enables the hydrolysis of organic phosphates to provide phosphate for mineralization. Second, the activation of osteogenesis signals keeps growth plate cartilage cells active and preparing for the next step of calcification. Collagen tripeptides accelerate bone formation and increase calcium deposition.Collagen fibers form the framework of the skeleton; hydroxyapatite crystals form the main matrix of the bone.

[0041] Egg yolk tripeptides / gelatin egg white powder: Egg yolk tripeptides are derived from the hydrolysis of egg yolks and contain seven amino acids closely associated with bone growth: glutamate, glycine, arginine, alanine, proline, leucine, and lysine. Studies show that egg yolk content increases the height of the epiphyseal plate and promotes elongation of the lower leg shaft.

[0042] Casein phosphopeptide: Phosphoproteins with activating peptide fragments, carrying a negative charge, possess mineral binding and carrier structures that enable mineral ions to remain soluble in the small intestine. It supports the solubility and absorption of calcium, zinc, and other ions. Casein phosphopeptide can stabilize free calcium ions within the intestinal lumen, forming stable complexes and reducing the tendency for calcium salt formation in the intestine, thus increasing the absorbable free calcium concentration through the mucosa.

[0043] In this device, casein phosphopeptide, together with vitamin D3 and vitamin K2, forms a fast track for calcium from the outside into the bone: After passing through the digestive tract, calcium enters the small intestine and, after binding to casein phosphopeptide, remains in solution without clumping with oxalic or phytic acid. Vitamin D3 promotes the active absorption of calcium in the small intestine and regulates the synthesis of calcium-binding proteins in the intestine. Vitamin K2 activates calcium-binding proteins in the bone, particularly osteocalcin, and directs calcium deposits into the bone matrix.

[0044] The present invention comprises the central active composition of the device: mineral combinations: calcium, magnesium, zinc; amino acid combinations: L-lysine, L-tryptophan or other amino acids; vitamin components: vitamin D3, vitamin K2, vitamin A; active peptide components: casein phosphopeptide, collagen tripeptides, egg yolk tripeptides / hydrolyzed egg yolk flour. This composition forms the basis of the invention; the administered dose depends on the shelf.

[0045] As is generally known in this field, the appropriate dosage depends on various factors, such as weight, age, sex, and stage of growth and development. The dosage regimen is determined by the amount of the administered dose, the patient's general health, and any other medications being taken concurrently. Accordingly, a suitable dosage strategy for the compound pharmacological composition of the invention can be established in consultation with the treating physician, taking into account the aforementioned factors.

[0046] According to the invention, the administered dose of the composition consisting of calcium, magnesium, zinc, L-lysine, L-tryptophan or other amino acids, vitamin D3, vitamin K2, vitamin A or other amino acids, casein phosphopeptide, collagen tripeptides, egg yolk tripeptides / hydrolyzed egg yolk flour comprises the following quantities: 100-500 mg calcium (based on calcium element, not calcium compound), 50-300 mg magnesium, 1-5 mg zinc, 100-500 mg L-lysine, 10-800 mg other amino acids or a combination of amino acids, 400-1000 IU vitamin D3, 0-1500 IU vitamin A, 10-30 µg vitamin K2, 50-500 mg collagen tripeptides, 5-100 mg egg yolk tripeptides / hydrolyzed egg yolk flour, 5-50 mg casein phosphopeptide, according to the invention.

[0047] In a further preferred embodiment, the administered dose of the composition consisting of calcium, magnesium, zinc, L-lysine, L-tryptophan, vitamin D3, vitamin K2, vitamin A or other amino acids, casein phosphopeptide, collagen tripeptides, egg yolk tripeptides / hydrolyzed egg yolk flour, is 250-500 mg calcium element, 100-300 mg magnesium, 1-5 mg zinc, 250-500 mg L-lysine, 10-800 mg other amino acids or amino acid combination, 400-1000 IU vitamin D3, 0-1500 IU vitamin A, 10-30 µg vitamin K2, 50-500 mg collagen tripeptides, 5-100 mg egg yolk tripeptides / hydrolyzed egg yolk flour, 5-100 mg casein phosphopeptide.

[0048] According to the invention, the active ingredients include, but are not limited to, the above combinations of ingredients.

[0049] According to the invention, the concentrations of the active ingredients correspond to the content that a product-specific smallest self-contained packaging unit can provide. The recommended daily dose is typically 1-2 of such smallest possible units.

[0050] According to the invention, calcium and magnesium sources should be used in the form of citrate.

[0051] According to the invention, further amino acids or amino acid combinations comprise at least one further amino acid, including but not limited to L-glutamine, tryptophan, arginine, leucine, glycine.

[0052] According to the invention, the composition may contain additives that increase the intended palatability and adjust the taste, such as pure water, sweeteners (sugar, sugar substitutes and artificial sweeteners), acidulants, fruit juices, flavorings, antioxidants, preservatives, natural or artificial flavorings, vegetable oils.

[0053] According to the invention, the aforementioned active composition can be contained in various products, e.g. in foods, foodstuffs or functional foods, nutritional supplements, dietary supplements, pharmaceutical products, as well as in solid, liquid or semi-solid preparations.

[0054] Furthermore, the above-mentioned composition of active ingredients can be in liquid, powder form or as granules and offered in dosage forms such as soft capsules or drinks. Cited patent literature CN101268835B

[0022] JP3708115B

[0023] RU2501553C2

[0024] US6106874A

[0025] Zitierte Nicht-Patentliteratur Laron, Z. (2001). Insulin-like growth factor 1 (IGF-1): a growth hormone. Molecular Pathology, 54(5), 311-316.

[0006] Kvist, O., Dallora, A. L., Nilsson, O., Anderberg, P., Berglund, J. S., Flodmark, C., & Diaz, S. (2020). A cross-sectional magnetic resonance imaging study of factors influencing growth plate closure in adolescents and young adults. Acta Paediatrica, 110(4), 1249-1256.

[0012] Sari, Y. O., Aminuddin, A., Hamid, F., Prihantono, P., Bahar, B., & Hadju, V. (2021). Malnutrition in children associated with low growth hormone (Gh) Levels. Gaceta Sanitaria, 35, S327-S329.

[0015] Gunarathne, R., Guan, X., Feng, T., Zhao, Y., & Lu, J. (2024). L-lysine dietary supplementation for childhood and adolescent growth: Promises and precautions. Journal of Advanced Research

[0028] Calcium metabolism, bone and metabolic bone diseases. (1975). In Springer eBooks.

[0030] Dutta, P., & Layton, A. T. (2024). Modeling Calcium and Magnesium Balance: Regulation by Calciotropic Hormones and Adaptations under Varying Dietary Intake. iScience, 27(11), 111077.

[0036] Leem, K. H., Kim, S., Lim, J., Park, H. J., Shin, Y. C., & Lee, J. S. (2023). Hydrolyzed collagen tripeptide promotes longitudinal bone growth in childhood rats via increases in Insulin-Like growth factor-1 and bone morphogenetic proteins. Journal of Medicinal Food, 26(11), 809-819.

[0041] Lv, S., Chen, Y., Wu, J., Zhao, M., He, R., Du, J., Ullah, S., Feng, F., & Wang, J. (2024). Hydrolyzed egg yolk powder promotes bone growth and development in rats: A multidimensional mechanistic study. Food Bioscience, 61, 104800.

[0042] Liu, G., Guo, B., Sun, S., Luo, M., Liu, F., Miao, J., Tang, J., Huang, Y., Cao, Y., & Song, M. (2021). Promoting the Calcium-Uptake Bioactivity of Casein Phosphopeptides in vitro and in vivo. Frontiers in Nutrition, 8.

[0043] 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] CN 101268835B [0023, 0054] JP 3708115 [0024, 0054] RU 2501553C2 [0025, 0054] US 6106874A [0026, 0054] Cited non-patent literature

[0000] Laron, Z. (2001). Insulin-like growth factor 1 (IGF-1): a growth hormone. Molecular Pathology, 54(5), 311-316

[0054] Kvist, O., Dallora, A. L., Nilsson, O., Anderberg, P., Berglund, J. S., Flodmark, C., & Diaz, S. (2020). A cross-sectional magnetic resonance imaging study of factors influencing growth plate closure in adolescents and young adults. Acta Paediatrica, 110(4), 1249-1256

[0054] Sari, Y. O., Aminuddin, A., Hamid, F., Prihantono, P., Bahar, B., & Hadju, V. (2021). Malnutrition in children associated with low growth hormone (Gh) Levels. Gaceta Sanitaria, 35, S327-S329

[0054] Gunarathne, R., Guan, X., Feng, T., Zhao, Y., & Lu, J. (2024). L-lysine dietary supplementation for childhood and adolescent growth: Promises and precautions. Journal of Advanced Research

[0054] Calcium metabolism, bone and metabolic bone diseases. (1975). In Springer eBooks.

[0030] Dutta, P., & Layton, A. T. (2024). Modeling Calcium and Magnesium Balance: Regulation by Calciotropic Hormones and Adaptations under Varying Dietary Intake. iScience, 27(11), 111077

[0054] Leem, K. H., Kim, S., Lim, J., Park, H. J., Shin, Y. C., & Lee, J. S. (2023). Hydrolyzed collagen tripeptide promotes longitudinal bone growth in childhood rats via increases in Insulin-Like growth factor-1 and bone morphogenetic proteins. Journal of Medicinal Food, 26(11), 809-819

[0054] Lv, S., Chen, Y., Wu, J., Zhao, M., He, R., Du, J., Ullah, S., Feng, F., & Wang, J. (2024). Hydrolyzed egg yolk powder promotes bone growth and development in rats: A multidimensional mechanistic study. Food Bioscience, 61, 104800

[0054] Liu, G., Guo, B., Sun, S., Luo, M., Liu, F., Miao, J., Tang, J., Huang, Y., Cao, Y., & Song, M. (2021). Promoting the Calcium-Uptake Bioactivity of Casein Phosphopeptides in vitro and in vivo. Frontiers in Nutrition, 8

[0054]

Claims

[1] Composition comprising a mineral combination: calcium, magnesium, zinc; an amino acid combination: L-lysine, L-tryptophan or other amino acids; a vitamin combination: vitamin D3, vitamin K2, vitamin A; a bioactive peptide combination: casein phosphopeptide, collagen tripeptides, egg yolk tripeptides / hydrolyzed egg yolk flour. [2] Composition according to claim 1, wherein the calcium content is 100-500 mg (based on calcium element, not calcium compound), the magnesium content is 50-300 mg, the zinc content is 1-5 mg, the L-lysine content is 100-500 mg, other amino acids or amino acid combinations are 10-800 mg, the vitamin D3 content is 400-1000 IU, the vitamin A content is 0-1500 IU, the vitamin K2 content is 10-30 µg, the collagen tripeptide content is 50-500 mg, the egg yolk tripeptide / hydrolyzed egg yolk flour content is 5-100 mg, and the casein phosphopeptide content is 5-50 mg. [3] Composition according to claim 1, wherein the calcium content is 250-500 mg, the magnesium content is 100-300 mg, the zinc content is 1-5 mg, the L-lysine content is 250-500 mg, other amino acids or amino acid combinations are 10-800 mg, the vitamin D3 content is 400-1000 IU, the vitamin A content is 0-1500 IU, the vitamin K2 content is 10-30 µg, the collagen tripeptide content is 50-500 mg, the egg yolk tripeptide / hydrolyzed egg yolk flour content is 5-100 mg, the casein phosphopeptide content is 5-100 mg. [4] Composition according to claim 1, wherein calcium and magnesium sources are derived from citrate compounds.