Composition for promoting bone growth in children and use thereof

Abstract

A composition for promoting bone growth in children and the use thereof. The composition comprises the following components in parts by weight: 10-50 parts of zinc-rich yeast, 60-190 parts of enzymatically hydrolyzed bone meal, 200-1000 parts of collagen peptide, and 0.5-10 parts of selenium-rich Cardamine violifolia extract or 0.0022-0.0438 parts of sodium selenite; and / or, 10-50 parts of zinc-rich yeast or 0.25-1.25 parts of zinc oxide, 5-20 parts of γ-aminobutyric acid, and 30-120 parts of L-lysine or isolated whey protein (on the basis of the content of L-lysine).

Description

A composition for promoting bone growth in children and its application

[0001] Cross-referencing

[0002] This application claims priority to Chinese Patent Application No. 202410933977.2, filed on July 11, 2024, entitled “A composition for promoting bone growth in children and its application thereto,” the entire disclosure of which is incorporated herein by reference. Technical Field

[0003] This invention belongs to the field of nutritional and health products, and in particular relates to a composition that promotes bone growth in children and its application. Background Technology

[0004] With social development and improved living standards, children's height is receiving increasing attention from parents and society. Height not only affects an individual's appearance but can also influence future career choices and social activities. Early identification and intervention are crucial for children with growth retardation. Paying attention to height issues and taking timely measures, such as improving nutrition, treating underlying diseases, and adjusting lifestyle habits, can promote healthy growth in children. Therefore, products and methods that promote children's bone growth have always been a hot topic in nutritional and medical research.

[0005] Currently, there are various products on the market designed to promote children's height growth. These products typically include nutritional supplements and growth hormone therapy drugs. In the field of research on children's height growth, the secretion of growth hormone (GH) is considered one of the key factors. Growth hormone therapy drugs act directly on growth hormone levels, promoting height growth through exogenous supplementation of growth hormone. They also function in organs such as the liver, further influencing overall growth and metabolism by promoting the production of insulin-like growth factor-1 (IGF-1). Nutritional supplements primarily provide minerals such as calcium, phosphorus, and magnesium, as well as nutrients such as vitamin D, to support normal bone nutrition.

[0006] While these products can help children's height growth to some extent, they also have some drawbacks. First, although growth hormone therapy drugs are highly effective, they are expensive and require long-term injections. Moreover, due to individual differences, supplementing with exogenous growth hormone may not promote bone growth in some children with short stature. In addition, the effects of functional nutritional foods often lack direct scientific evidence.

[0007] Children's height growth is a complex biological process influenced by genetics, nutrition, hormone levels, and environmental factors. Longitudinal bone growth primarily relies on the epiphyseal growth plate, whose active growth plays a crucial role in this process. The growth plate consists of a proliferative zone that promotes the proliferation of chondrocytes and a maturation hypertrophic zone that allows chondrocytes to mature and enlarge.

[0008] During the critical periods of a child's growth, especially the preschool and early puberty years of age (3-11 years), the activity of the growth plate plays a decisive role in height growth. Nutritional intervention during this period is considered the golden period for promoting children's height growth because the chondrocytes of the growth plate are most active and most sensitive to nutritional and hormonal stimulation at this time.

[0009] Existing intervention products for children's height growth mainly focus on puberty and its later stages, with interventions during this period often emphasizing growth hormone supplementation or improved nutritional status to promote growth. However, for early intervention during the critical growth period of 3-11 years old, there are relatively few products on the market, and those that exist lack specificity. Existing products often lack designs tailored to the growth and development characteristics of children in this age group, failing to fully utilize the biological advantages of the active growth plate period in children's bones. During childhood, physical development increases rapidly, reaching peak bone mass, requiring sufficient nutritional intake and adequate secretion of endogenous growth hormone.

[0010] In conclusion, although there are already many products on the market that promote children's height growth, there is still room for improvement. In particular, there is a lack of products on the market that can comprehensively consider the secretion of endogenous growth hormone, effectively enhance the activity of the epiphyseal growth plate, and ultimately promote the supplementation of nutrients needed for bone growth. Summary of the Invention

[0011] This invention proposes a uniquely formulated composition that can enhance the endogenous secretion of growth hormone in children, especially those aged 3-11 years in the preschool and early puberty stages, directly increasing the activity of bone growth plates and thus promoting the growth rate and quality of children's bones.

[0012] The first objective of this invention is to provide a natural, safe, effective composition that promotes bone growth in children.

[0013] As one of the technical solutions, the present invention provides a composition A for promoting bone growth in children. By weight, composition A comprises the following components: 10-50 parts of zinc-enriched yeast, 60-190 parts of enzymatically hydrolyzed bone powder, 200-1000 parts of collagen peptides, and 0.5-10 parts of selenium-enriched corydalis leaf extract or 0.0022-0.0438 parts of sodium selenite.

[0014] Preferably, by weight, composition A comprises the following components (more preferably composed of the following components): 22.5-35 parts of zinc-enriched yeast, 80-140 parts of enzymatically hydrolyzed bone meal, 450-750 parts of collagen peptides, and 0.5-2.5 parts of selenium-enriched corydalis leaf extract or 0.0022-0.0110 parts of sodium selenite.

[0015] Among the above components, the main active ingredient in zinc-enriched yeast is organic zinc. As a highly bioavailable natural zinc source, zinc-enriched yeast participates in the interaction of numerous enzymes, increases osteoblast DNA expression, and stimulates Runx2 / Cbfa1 expression, thereby increasing osteoblast differentiation and osteoclast formation. Organic zinc also plays a physiological role in synergistically stimulating bone growth with IGF-I or TGF-β. Furthermore, organic zinc can bind to growth hormone, maintaining its structure and function. Organic zinc interacts with growth hormone itself to form a more stable dimer form, thereby regulating growth hormone signal transduction.

[0016] The zinc-enriched yeast of the present invention preferably has an organic zinc content of not less than 0.2%, and is a known commercially available product, such as Angel Yeast Co., Ltd., which has an organic zinc content of 2%.

[0017] Among the above components, the enzymatically hydrolyzed bone powder is a bone powder containing chondroitin sulfate and collagen, prepared by enzymatic hydrolysis and separation extraction of bovine cartilage. Preferably, the chondroitin sulfate content in the enzymatically hydrolyzed bone powder is not less than 80%.

[0018] The main active ingredient in enzymatically hydrolyzed bone meal is chondroitin sulfate, a major component of joints that supports joint health and helps prevent arthritis. In articular cartilage, chondroitin sulfate often aggregates with hyaluronic acid and proteins to form large complexes, which are the main load-bearing proteoglycans in cartilage tissue and are crucial for bone development. The high chondroitin sulfate content in proteoglycans plays a major role in allowing cartilage to resist tensile stress under various load conditions by providing resistance and elasticity to the tissue, and also helps reduce bone resorption.

[0019] The enzymatically hydrolyzed bone powder used in this invention can be a known commercially available product, such as Mattel Technology (Qingdao) Co., Ltd., which has a chondroitin sulfate content of approximately 90%.

[0020] Of the components mentioned above, collagen peptides provide the building blocks for bone. During bone remodeling, collagen peptides provide the necessary building blocks to support bone formation, acting as messengers and actively promoting osteoblast activity. Collagen peptides can dose-dependently support osteoblast proliferation, a crucial first step in bone formation.

[0021] Among the above components, the selenium-enriched Viola yedoensis extract is made from Viola yedoensis grown in Enshi region through processes such as crushing, extraction, and drying, and preferably has a selenium content of not less than 0.1%.

[0022] The main active ingredient of the selenium-enriched *Viola yezoensis* leaf extract of this invention is selenium in amino acid form, including selenocysteine / selenocysteine, methylselenocysteine, and selenomethionine. Selenocysteine ​​is an essential amino acid for the formation of selenoenase. Conventional extraction methods that can enrich selenium and meet edible requirements are acceptable, such as water extraction or ethanol extraction, or the use of commercially available products. In this embodiment of the invention, a commercially available selenium-enriched *Viola yezoensis* leaf extract with a selenium content of approximately 0.2% is used.

[0023] Among the above components, zinc, chondroitin sulfate, selenium, and collagen peptides can be combined in their respective conventional intake amounts, preferably in a weight ratio of 0.2-1:60-190:0.001-0.02:200-1000, and more preferably in a weight ratio of 0.45-0.7:80-140:0.001-0.005:450-750.

[0024] Composition A of the present invention is based on natural ingredients, avoiding the potential risks of drug treatment, and provides children with a natural and safe composition that supplements key nutrients for bone growth, promotes osteoblast growth, improves bone metabolism, and promotes children's bone growth.

[0025] The composition A provided by this invention can be designed into various forms that are easily accepted by children, such as powder, granules, tablets, capsules, liquid beverages, or oral solutions, thereby improving compliance with children and parents. Preferably, composition A is a powder, granules, or tablet.

[0026] As a second technical solution, the present invention provides a composition B for promoting bone growth in children. By weight, composition B comprises the following components: 10-50 parts of zinc-enriched yeast or 0.25-1.25 parts of zinc oxide, 5-20 parts of γ-aminobutyric acid, and 30-120 parts of L-lysine or whey protein isolate (based on L-lysine content).

[0027] Preferably, by weight, composition B comprises the following components (more preferably composed of the following components): 22.5-35 parts of zinc-enriched yeast or 0.563-0.875 parts of zinc oxide, 9-15 parts of γ-aminobutyric acid, and 45-75 parts of L-lysine or whey protein isolate (based on L-lysine content).

[0028] Among the above components, γ-aminobutyric acid can stimulate and promote the arcuate nucleus and ventromedial nucleus of the hypothalamus, increase the secretion of growth hormone-releasing hormone (GHRH), thereby increasing the release of pituitary GH and subsequent IGF-1, and promoting bone growth.

[0029] Among the above components, L-lysine can stimulate the pituitary gland to secrete more growth hormone, IGF-1, and growth hormone-releasing hormone, thereby promoting bone growth. L-lysine may be derived from chemically or biologically synthesized substances, or it can be derived from whey protein, whey protein isolate, casein, or milk protein containing L-lysine, wherein the L-lysine content can be 2%, 5%, 8%, or 10% or more. In one embodiment, the L-lysine in composition B is preferably whey protein isolate containing L-lysine, and its L-lysine content is preferably at least 10%.

[0030] Among the above components, zinc, γ-aminobutyric acid and L-lysine can be the combination of their respective conventional intakes, preferably in a weight ratio of 0.2-1:5-20:30-120, more preferably in a weight ratio of 0.45-0.7:9-15:45-75.

[0031] Composition B of the present invention can promote the secretion of growth hormone in the body, effectively enhance the activity of the epiphyseal growth plate, and thus accelerate the growth rate of bones.

[0032] Similarly, the composition B provided by this invention can be designed into various forms that are easily accepted by children, such as powder, granules, tablets, capsules, liquid beverages, or oral solutions, thereby improving compliance with children and parents. Preferably, the composition B is a powder, granules, or tablet.

[0033] As another more preferred technical solution, the present invention provides a composition C for promoting bone growth in children, which comprises the above-mentioned composition A and composition B.

[0034] Specifically, by weight, composition C comprises the following components:

[0035] (1) 10-50 parts of zinc-enriched yeast, 60-190 parts of enzymatically hydrolyzed bone meal, 200-1000 parts of collagen peptides and 0.5-10 parts of selenium-enriched violet leaf and rice barley extract or 0.0022-0.0438 parts of sodium selenite;

[0036] (2) 10-50 parts of zinc-enriched yeast or 0.25-1.25 parts of zinc oxide, 5-20 parts of γ-aminobutyric acid, and 30-120 parts of L-lysine or whey protein isolate (based on L-lysine content).

[0037] Preferably, composition C comprises, by weight, the following components:

[0038] (1) 22.5-35 parts of zinc-enriched yeast, 80-140 parts of enzymatically hydrolyzed bone meal, 450-750 parts of collagen peptides and 0.5-2.5 parts of selenium-enriched violet leaf and rice barley extract or 0.0022-0.0110 parts of sodium selenite;

[0039] (2) 22.5-35 parts of zinc-enriched yeast or 0.563-0.875 parts of zinc oxide, 9-15 parts of γ-aminobutyric acid, and 45-75 parts of L-lysine or whey protein isolate (based on L-lysine content).

[0040] It is worth noting that in the composition C described in this invention, composition A and composition B can be mixed into a formulation; or they can be formulated separately as independent components and consumed separately. Composition A can be consumed at any time, and composition B is consumed before bedtime.

[0041] Growth hormone secretion is most active during deep sleep at night, especially in the first few hours after falling asleep. This period is known as slow-wave sleep or non-rapid eye movement sleep, during which the pulsed release of growth hormone peaks. Simultaneously, children's bone growth is most active during nighttime sleep.

[0042] This invention utilizes a rational combination of nutrients such as zinc-rich yeast or zinc oxide, enzymatically hydrolyzed bone meal, selenium-rich violet leaf and rice barley extract or sodium selenite, collagen peptides, L-lysine, and γ-aminobutyric acid to create a composition that can exogenously supplement nutrients for bone growth, promote the secretion of endogenous growth hormone, and increase the activity of bone growth plates, thereby promoting bone growth.

[0043] The above-mentioned composition C, as a preferred embodiment, exhibits better effects in promoting and stimulating the secretion of growth hormone in the body, effectively enhancing the activity of the epiphyseal growth plate, supplementing the specific nutrients required by the bone and growth plate, thereby accelerating the growth rate of the bone.

[0044] A second objective of this invention is to provide the use of the above-mentioned compositions A, B, and C in the preparation of foods, pharmaceuticals, or health products that promote bone growth in children, wherein the foods include health foods and foods for special medical purposes.

[0045] This invention also provides a method of using the above-mentioned composition for promoting bone growth in children, comprising: consuming composition A at any time during the day; and consuming composition B two hours before bedtime. Taking composition B before bedtime can enhance growth hormone secretion during sleep and promote active bone growth in the growth plates.

[0046] According to embodiments of the present invention, the dosage form of the above-mentioned food (including health food, special medical purpose formula food), medicine or health product may be powder, granules, tablets, capsules, liquid beverage or oral liquid, etc., preferably powder, granules or tablets.

[0047] It should be noted that when the composition provided by the present invention is further formulated into food, pharmaceuticals, or health products, it may further include excipients acceptable in the formulation of food, pharmaceuticals, or health products. Specifically, it may include excipients, lubricants, preservatives, fillers, solubilizers, stabilizers, modified milk powder, fruit juice powder, sweeteners, flavorings, etc., such as polyglucan, fructooligosaccharides, xylitol, sorbitol, milk powder, lactose, steviol glycosides, mogrosides, taro powder, fruit powder, resistant dextrin, cocoa powder, glucose, sucrose, sorbitol, mannitol, xylitol, galactooligosaccharides, erythritol, maltitol, starch, hydroxypropyl cellulose, gum arabic, alginate, agar, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, crospovidone, water, methylparaben, propylparaben, talc, sodium stearate, and mineral oil, etc. Furthermore, the present invention can further adjust the proportion of each component according to the specific nutritional needs of children, or add other beneficial components, such as vitamin D and vitamin K, to enhance the product's effectiveness.

[0048] The composition for promoting children's bone growth provided by this invention, through the combination of specific nutrients and other bioactive ingredients, can effectively stimulate the secretion of growth hormone in the body, avoiding the side effects and compliance problems of exogenous growth hormone therapy. Animal experiments have verified that the composition for promoting children's bone growth provided by this invention can effectively enhance the activity of the epiphyseal growth plate, supplement the specific nutrients required by the bone and growth plate, and promote the proliferation and differentiation of the proliferative and hypertrophic layers in the growth plate region, thereby accelerating bone growth and providing children with a more comprehensive, safe, and effective support solution for height growth. Detailed Implementation

[0049] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention. In the following embodiments, 1 part = 10g.

[0050] The source information of each raw material used in this invention is as follows:

[0051] Zinc oxide: purchased from Nantong Licheng Bioengineering Co., Ltd.

[0052] Zinc-enriched yeast: Angel Yeast Co., Ltd.

[0053] γ-Aminobutyric acid: Bloomage Biotechnology Co., Ltd.

[0054] L-Lysine: Nantong Zilang Biomedical Technology Co., Ltd.

[0055] Whey protein isolate: Shanghai Gexin Food Technology Co., Ltd.

[0056] Enzymatically hydrolyzed bone meal: Mattel Technology (Qingdao) Co., Ltd.

[0057] Selenium-enriched Viola leaf and Capsicum sylvestris extract: Hubei Xizhuangwang Food Co., Ltd.

[0058] Sodium selenite: Nantong Licheng Bioengineering Co., Ltd.

[0059] Collagen peptides: Chengshan Industrial (Shanghai) Co., Ltd.

[0060] Examples of nutrient content in the following embodiments are as follows:

[0061] Zinc oxide: Zinc content approximately 80%

[0062] Zinc-enriched yeast: Zinc content approximately 2%

[0063] Enzymatically hydrolyzed bone meal: Chondroitin content approximately 95%.

[0064] Sodium selenite: Selenium content approximately 45%.

[0065] Selenium-enriched Viola leaf extract: Selenium content approximately 0.2%.

[0066] Example 1

[0067] This embodiment provides a composition B for promoting bone growth in children, which, by weight, consists of the following components: 0.375 parts zinc oxide, 5 parts γ-aminobutyric acid, and 30 parts L-lysine.

[0068] This embodiment also provides a specific method for preparing the above-mentioned raw materials into powder, as follows:

[0069] Zinc oxide, γ-aminobutyric acid, and L-lysine were pulverized separately using a pulverizer and passed through a 60-mesh sieve to obtain a single dose of 0.36g that can be directly dissolved in water.

[0070] Example 2

[0071] This embodiment provides a composition B for promoting bone growth in children, which, by weight, consists of the following components: 15 parts zinc-rich yeast, 5 parts γ-aminobutyric acid, and 30 parts L-lysine.

[0072] This embodiment also provides a specific method for preparing the above-mentioned raw materials into powder, as follows:

[0073] Zinc-enriched yeast, γ-aminobutyric acid, and L-lysine were pulverized separately using a grinder and passed through a 60-mesh sieve to obtain a single dose of 0.5g that can be directly dissolved in water and taken.

[0074] Example 3

[0075] This embodiment provides a composition B for promoting bone growth in children, which, by weight, consists of the following components: 30 parts of zinc-enriched yeast, 10 parts of γ-aminobutyric acid, and 60 parts of L-lysine.

[0076] This embodiment also provides a specific method for preparing the above-mentioned raw materials into powder, as follows:

[0077] Zinc-enriched yeast, γ-aminobutyric acid, and L-lysine were pulverized separately using a pulverizer and passed through a 60-mesh sieve to obtain a single dose of 1g that can be directly dissolved in water and taken orally.

[0078] Example 4

[0079] This embodiment provides a composition B for promoting bone growth in children, which, by weight, consists of the following components: 30 parts of zinc-enriched yeast, 10 parts of γ-aminobutyric acid, and 600 parts of whey protein isolate (calculated as L-lysine content 10%).

[0080] This embodiment also provides a specific method for preparing the above-mentioned raw materials into powder, as follows:

[0081] Zinc-enriched yeast, γ-aminobutyric acid, and isolated whey protein were pulverized separately using a grinder and passed through a 60-mesh sieve to obtain a single dose of 6.4g that can be directly dissolved in water and taken.

[0082] Example 5

[0083] This embodiment provides a composition A for promoting bone growth in children, which, by weight, consists of the following components: 15 parts zinc-enriched yeast, 50 parts enzymatically hydrolyzed bone powder, 250 parts collagen peptides, and 0.0027 parts sodium selenite.

[0084] This embodiment also provides a specific method for preparing the above-mentioned raw materials into powder, as follows:

[0085] Zinc-enriched yeast, enzymatically hydrolyzed bone meal, sodium selenite, and collagen peptides were pulverized separately using a pulverizer and passed through a 60-mesh sieve to obtain a single dose of 3.15g that can be directly dissolved in water and taken.

[0086] Example 6

[0087] This embodiment provides a composition A for promoting bone growth in children, which, by weight, consists of the following components: 15 parts zinc-rich yeast, 50 parts enzymatically hydrolyzed bone meal, 250 parts collagen peptides, and 0.625 parts selenium-rich violet leaf and rice barley extract.

[0088] This embodiment also provides a specific method for preparing the above-mentioned raw materials into powder, as follows:

[0089] Zinc-rich yeast, enzymatically hydrolyzed bone meal, selenium-rich violet leaf and rice barley extract, collagen peptides, etc., were pulverized separately using a pulverizer and passed through a 60-mesh sieve to obtain a single dose of 3.16g that can be directly dissolved in water and taken.

[0090] Example 7

[0091] This embodiment provides a composition A for promoting bone growth in children, which, by weight, consists of the following components: 30 parts zinc-rich yeast, 100 parts enzymatically hydrolyzed bone powder, 500 parts collagen peptides, and 1.25 parts selenium-rich violet leaf and rice barley extract.

[0092] This embodiment also provides a specific method for preparing the above-mentioned raw materials into powder, as follows:

[0093] Zinc-enriched yeast, enzymatically hydrolyzed bone meal, selenium-enriched violet leaf and rice barley extract, collagen peptides, etc., were pulverized separately using a pulverizer and passed through a 60-mesh sieve to obtain a single dose of 6.31g that can be directly dissolved in water.

[0094] Example 8

[0095] This embodiment provides a composition for promoting bone growth in children. By weight, the raw materials consist of the following components: 60 parts of zinc-enriched yeast, 100 parts of enzymatically hydrolyzed bone meal, 500 parts of collagen peptides, 1.25 parts of selenium-enriched corydalis leaf extract, 10 parts of γ-aminobutyric acid, and 600 parts of whey protein isolate (based on an L-lysine content of 10%).

[0096] This embodiment also provides a specific method for preparing the above-mentioned raw materials into powder, as follows:

[0097] Zinc-enriched yeast, enzymatically hydrolyzed bone meal, collagen peptides, selenium-enriched violet leaf and rice barley extract, γ-aminobutyric acid, and isolated whey protein were pulverized separately using a pulverizer and passed through a 60-mesh sieve to obtain a single dose of 12.7g that can be directly dissolved in water.

[0098] Table 1

[0099] Experiment 1: Animal Experiment

[0100] 1. Laboratory animals

[0101] Three-week-old, SPF-grade male Sprague Dawley rats were purchased from a commercial company and housed in polycarbonate cages measuring 46.5cm x 30cm x 18cm (length x width x height). Each cage contained a maximum of four animals of the same sex. The laboratory animal facility was equipped with a fresh air-barrier environment, with environmental conditions controlled at 20–24°C and 40%–70% relative humidity. Temperature and humidity were monitored in real-time using thermometers and hygrometers. Lighting in the animal housing was controlled by an electronic timer system, with lights on for 12 hours and off for 12 hours daily (8:00 AM to 8:00 PM). Animals had free access to standard experimental feed and water during the experiment. Animals were acclimatized to the facility for one week prior to the experiment.

[0102] 2. Experimental Grouping

[0103] Rats were randomly divided into 9 groups using a randomized block design, including one control group and eight experimental groups, with 8 rats in each group. The control group received 0.5 ml / kg saline once daily at a fixed time. The experimental groups received the compositions from Examples 1-8 once daily at a fixed time. The rats were administered the compositions via gavage. The experiment lasted for 4 weeks.

[0104] 3. The dosage Z used in the animal experiments was calculated according to the following formula:

[0105] Z (gavage dose) = X (dose administered per unit body weight, g / kg) * M (rat body weight, kg) * 0.21

[0106] Table 2 shows the schemes using different compositions from the examples. The values ​​in the table represent the dosage per unit body weight X g / kg for each example.

[0107] Examples 1, 2, 3, and 4 primarily screened different compositions B. Examples 5, 6, and 7 screened different compositions A. Example 8 involved the combined use of compositions A and B (equivalent to composition C).

[0108] Table 2

[0109] 4. Animal weight and feed consumption

[0110] All animals were weighed once before the first gavage, twice a week during the experiment, and once at the end of the experiment. Daily food intake was recorded and total food utilization was calculated.

[0111] 5. Sample Collection

[0112] On the last day of week 4, the experimental animals were treated with carbon dioxide (end of the experiment), and blood was drawn from the heart using a syringe. The collected whole blood was processed according to the blood sample testing requirements of the kit. The resulting serum was transferred to new labeled centrifuge tubes and stored at -60 to -80°C or below.

[0113] After blood collection, the abdomen was immediately opened to remove the heart, liver, kidneys, and spleen, and their weight was measured and observed using a light microscope.

[0114] 6. Growth hormone testing

[0115] The serum samples collected above were tested using a growth hormone kit, an IGF-1 kit, and an insulin-like growth factor binding protein (IGF-BP3) kit.

[0116] 7. Nutrient testing

[0117] The levels of zinc, selenium, and L-lysine in the collected serum samples were measured.

[0118] 8. Tibial length and bone mineral density measurement

[0119] At the end of the experiment, the left tibia of the animal was soaked in 4% neutral paraformaldehyde, and the tibia length, growth plate thickness, and bone mineral density (BMD) were measured.

[0120] 9. Pathological examination and immunohistochemical detection

[0121] At the end of the experiment, the left growth plate of the animal was taken for H&E staining and pathological analysis to compare the lengths of the proliferative layer and the hypertrophic layer of the growth plate.

[0122] Immunohistochemical analysis was performed on the right growth plate to measure the expression of growth hormone, IGF-1, and IGF-BP3 in the growth plate.

[0123] 10. Weight changes and food consumption

[0124] Table 3 shows the changes in body weight, feed intake, and feed utilization of the rats after 4 weeks of feeding. The daily intake of the nutrient composition showed a more significant increase in body weight compared to the control group, with Example 8 showing the best results.

[0125] Table 3 Food utilization rate = (weight gain / feed intake) * 100

[0126] 11. Organ weight and toxicological light microscopic observation

[0127] After 4 weeks of feeding, the organs removed from the rats were compared. The results showed that there was no significant difference in the weight of the liver, kidney, spleen and heart between Example 8 with the highest dose and the blank group.

[0128] When observed under a light microscope, compared with Example 8, the blank group showed that the myocardial fibers were arranged regularly, the longitudinal and transverse striations were clearly visible, the endometrial and intermembrane structures were intact, the myocardial nucleus was clearly visible, and the myocardial interstitial blood vessels were not significantly dilated.

[0129] The liver lobule structure was clear, the hepatocytes were neatly arranged, and no hepatocyte degeneration or necrosis was observed. The central vein and hepatic sinusoids were not significantly dilated, and no inflammatory cell infiltration was observed in the portal area.

[0130] The glomeruli are intact, the renal tubular structure is clear and normal, there is no obvious swelling or necrosis of the renal tubular epithelial cells, and there is no congestion or inflammatory cell infiltration in the renal interstitium and glomeruli.

[0131] The spleen's histological structure was clear, with orderly arrangement of splenic corpora. No splenic cell degeneration or necrosis was observed. The dilation of splenic sinuses and splenic cords was not obvious, and the boundary between the red and white pulp was clear. The distribution of lymphocytes in the central artery and surrounding areas of the splenic corpora was normal, with no abnormal cell infiltration observed. There was no significant edema or hemorrhage in the splenic interstitium, and the overall tissue structure was intact, with no obvious signs of toxic damage.

[0132] In Example 8, no pathological changes were observed in any of the tissues compared to the control group.

[0133] 12. Increase in tibial length

[0134] The tibial length measurements (see Table 4) show that the bone growth rate in the control group was significantly slower than that in the experimental group. Oral administration of nutritional compositions A and B increased the tibial growth rate. In particular, the combined use of nutritional compositions A and B significantly increased the longitudinal bone growth rate, with Example 8 showing the fastest growth rate.

[0135] Table 4

[0136] 13. Growth hormone

[0137] After detecting serum growth hormone, IGF-1, and IGF-BP3 in the samples (see Table 5), compared with the control group, the experimental group showed significantly higher levels of serum GH, IGF-1, and IGF-BP3, indicating that oral nutritional composition B can promote the secretion of endogenous growth hormone. In particular, the combined use of nutritional composition A and composition B can most effectively increase the secretion of endogenous growth hormone.

[0138] Table 5

[0139] 14. Serum Nutrient Content

[0140] The results of testing the zinc, selenium, and L-lysine content in the collected serum samples (see Table 6) show that the L-lysine in Composition B can be absorbed by the body, thereby significantly increasing the L-lysine concentration in the serum. Oral nutritional compositions A and B can promote the absorption and utilization of zinc and selenium in the blood.

[0141] Table 6

[0142] 15. Bone mineral density measurement

[0143] The bone mineral density (BMD) results of the collected bone samples (see Table 7) show that oral nutritional compositions A and B can improve cortical bone mineral density and thus improve the quality of bone growth while promoting bone growth. In particular, the combined use of compositions A and B yields the best results.

[0144] Table 7

[0145] 16. Growth plate height

[0146] The results of the bone growth plate sample analysis (see Table 8) show that, compared with the control group, the bone growth plates in Examples 1 to 8, including the proliferative and hypertrophic zones, were thicker. The growth plate consists of four distinct histological regions, starting from the quiescent zone, passing through the proliferative, hypertrophic, and ossification zones. The proliferative zone is the driving force for bone elongation. After several mitotic divisions, chondrocytes transform into the hypertrophic zone. In the ossification zone, chondrocytes eventually die and transform into bone matrix, where longitudinal bone growth occurs. The height of the growth plate is regulated by the proliferative and hypertrophic chondrocyte regions. Therefore, the height of the growth plate is direct evidence of longitudinal bone growth. The increase in the growth plate in the experimental groups indicates that nutrient compositions A and B can increase the length of the growth plate responsible for transforming into bone matrix, where longitudinal bone growth occurs.

[0147] In particular, composition B has a stronger effect on promoting the activity of the growth plate, and the combined use of nutrient composition A and composition B can significantly increase the thickness of each area of ​​the production plate.

[0148] Table 8

[0149] 17. Immunohistochemical detection of growth plates

[0150] Immunohistochemical analysis of the growth plate samples showed (see Table 9) that, compared with the control group, the experimental group showed higher expression of IGF-1 and IGF-BP3 in the bone growth plate, and nutrient composition B could significantly increase the expression of IGF-1 and IGF-BP3 in the growth plate.

[0151] Bone tissue is rich in growth factors involved in regulating bone development and growth. Among these factors, IGF-1 is considered to play a crucial role in bone metabolism. IGF-1 stimulates type I collagen synthesis, increases the rate of matrix deposition, and inhibits collagen degradation, thereby forming new bone. The growth-promoting effect of IGF-1 is associated with increased chondrocyte proliferation and survival. Accordingly, IGF-1 is highly expressed in hypertrophic and ossified areas.

[0152] IGF-BP3 is considered a biochemical indicator of GH levels, and its production and maintenance depend on growth hormone. Under normal circumstances, growth hormone levels affect IGF-BP3 levels. IGF-BP3 can bind to circulating IGF-1, and through this binding, it can prolong the half-life of IGF in the blood, reduce their degradation, and also regulate their binding to their receptors, thereby affecting the biological activity of IGF.

[0153] These results indicate that the oral nutritional composition B can regulate circulating IGF-1 and IGF-BP3, thereby promoting growth by increasing GH secretion and having a direct effect on the proximal growth plate of bone.

[0154] Table 9

[0155] The above experimental results show that the difference between Example 1 and Example 2 is that Example 1 used chemically synthesized inorganic zinc oxide, while Example 2 used organic yeast zinc. The zinc intake content of Example 1 and Example 2 is the same. The results show that the organic zinc in Example 2 has better bioavailability and better results in promoting bone growth plate activity.

[0156] The above experimental results show that the difference between Example 5 and Example 6 is that Example 5 used sodium selenite, which is a chemically synthesized inorganic selenium source, while Example 6 used amino acid selenium, which is an organic selenium source from Corydalis yanhusuo. The selenium content of Examples 5 and 6 is the same. The results show that the organic selenium in Example 6 has better bioavailability and shows certain effects on bone density and bone growth rate.

[0157] The above experimental results show that the difference between Example 3 and Example 4 is that Example 3 used L-lysine, while Example 4 used whey protein isolate containing L-lysine. The L-lysine content of Example 3 and Example 4 is the same. The results show that whey protein isolate containing L-lysine promotes bone growth and development more strongly than L-lysine alone, and can also promote the absorption and utilization of other nutrients.

[0158] Formulation example:

[0159] Example 9

[0160] This embodiment provides a granule for promoting bone growth in children and its specific preparation method, as follows:

[0161] 1. The composition described in Example 7 is pulverized using a pulverizer, passed through a 60-mesh sieve, and then added to a three-dimensional mixer and mixed for 10 minutes to obtain a premixed powder.

[0162] 2. Then, mix the above premixed powder with the modified milk powder, fructooligosaccharides, xylitol, peach juice powder, flavoring and stevioside in a ratio of 6:2:1:1:0.1:0.1 for 10 minutes, and then place it in a dry granulator to obtain composite granules.

[0163] 3. Granulate the composite granules using a 14-mesh sieve to obtain granules, which can then be packaged and sealed in 10g bags.

[0164] Example 10

[0165] This embodiment provides a granule for promoting bone growth in children and its specific preparation method, as follows:

[0166] 1. The composition described in Example 4 is pulverized using a pulverizer, passed through a 60-mesh sieve, and then added to a three-dimensional mixer and mixed for 10 minutes to obtain a premixed powder.

[0167] 2. Then, mix the above premixed powder with fructooligosaccharides, whole milk powder, strawberry juice powder, flavoring and steviol glycosides in a ratio of 6:2:1.5:0.5:0.2:0.1 for 10 minutes, and then place it in a dry granulator to obtain composite granules.

[0168] 3. Granulate the composite granules using a 14-mesh sieve to obtain granules, which can then be packaged and sealed in 10g bags.

[0169] Example 11

[0170] This embodiment provides a powder for promoting bone growth in children and its specific preparation method, as follows:

[0171] 1. The composition described in Example 7 is pulverized using a pulverizer, passed through a 60-mesh sieve, and then added to a three-dimensional mixer and mixed for 10 minutes to obtain a premixed powder.

[0172] 2. Then, mix the above premixed powder with the modified milk powder, fructooligosaccharides, xylitol, peach juice powder, flavoring and stevioside in a ratio of 6:2:1:1:0.1:0.1 for 10 minutes to obtain a powder that can be directly dissolved in water.

[0173] 3. Divide the powder into 10g bags and seal them.

[0174] Example 12

[0175] This embodiment provides a powder for promoting bone growth in children and its preparation method, as follows:

[0176] 1. The composition described in Example 4 is pulverized using a pulverizer, passed through a 60-mesh sieve, and then added to a three-dimensional mixer and mixed for 10 minutes to obtain a premixed powder.

[0177] 2. Then, mix the above premixed powder with fructooligosaccharides, whole milk powder, strawberry juice powder, flavoring and stevioside in a ratio of 6:2:1.5:0.5:0.2:0.1 for 10 minutes to obtain a powder that can be directly dissolved in water.

[0178] 3. Divide the powder into 10g bags and seal them.

[0179] Example 13

[0180] This embodiment provides a tablet for promoting bone growth in children and its specific preparation method, as follows:

[0181] 1. The composition described in Example 7 is further modified by adding 30 parts of maltodextrin and mixing it in a three-dimensional mixer for 10 minutes to obtain a premixed powder.

[0182] 2. Add the above premixed powder to a wet granulator, add an appropriate amount of 60% ethanol to make a soft material, granulate it through a 20-mesh sieve, dry it at 50°C for 2 hours until the moisture content of the granules is 3-5%, granulate the dried granules through a 16-mesh sieve, and package them to obtain composite granules for later use.

[0183] 3. Mix the above-mentioned composite granules with sorbitol and magnesium stearate in a ratio of 50:48.5:1.5 using a three-dimensional mixer until uniform, and compress the mixture into tablets using a tableting machine to obtain tablets of 1.5g / tablet.

[0184] 4. Dispense the tablets into bottles of 60 tablets each and seal them.

[0185] Example 14

[0186] This embodiment provides a tablet for promoting bone growth in children and its specific preparation method, as follows:

[0187] 1. The composition described in Example 7 is further modified by adding 30 parts of maltodextrin and mixing it in a three-dimensional mixer for 10 minutes to obtain a premixed powder.

[0188] 2. Take the above premixed powder, add it into a wet granulator, add an appropriate amount of 60% ethanol to make a soft material, granulate it through a 20-mesh sieve, dry it at 50℃ for 2 hours, dry it until the moisture content in the granules is 3-5%, granulate the dried granules through a 16-mesh sieve, and package them to obtain composite granules for later use.

[0189] 3. Mix the above-mentioned composite granules with sorbitol and magnesium stearate in a ratio of 50:48.2:1.8 using a three-dimensional mixer; compress the mixture into tablets using a tablet press to obtain tablets of 1.5g / tablet.

[0190] 4. Dispense the tablets into bottles of 60 tablets each and seal them.

[0191] Example 15

[0192] This embodiment provides a composition C for promoting bone growth in children, which consists of compositions A and B prepared in Examples 9 and 10.

[0193] In addition to the examples above, a premixed powder containing zinc-enriched yeast, gamma-aminobutyric acid, L-lysine, enzymatically hydrolyzed bone meal, selenium-enriched violet leaf and rice barley extract, and collagen peptides in the proportions mentioned above can be further formulated into capsules, oral liquids, or other forms that are convenient for children to take.

[0194] Examples 16-23

[0195] Examples 16-23 provide compositions that promote bone growth in children, and their specific formulations are shown in Table 10.

[0196] Table 10

[0197] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention. Industrial applicability

[0198] This invention provides a composition for promoting bone growth in children and its application. The composition, by weight, comprises the following components: 10-50 parts of zinc-enriched yeast, 60-190 parts of enzymatically hydrolyzed bone meal, 200-1000 parts of collagen peptides, and 0.5-10 parts of selenium-enriched corydalis leaf extract or 0.0022-0.0438 parts of sodium selenite; and / or, 10-50 parts of zinc-enriched yeast or 0.25-1.25 parts of zinc oxide, 5-20 parts of γ-aminobutyric acid, and 30-120 parts of L-lysine or isolated whey protein (based on L-lysine content). This invention, through the rational combination of nutrients such as zinc-rich yeast, enzymatically hydrolyzed bone meal, selenium-rich violet leaf and rice barley extract, collagen peptides, L-lysine, and γ-aminobutyric acid, produces a composition that can exogenously supplement nutrients for bone growth, promote the secretion of endogenous growth hormone, and increase the activity of bone growth plates, thereby promoting bone growth. It has good economic value and application prospects.

Claims

1. A composition A for promoting bone growth in children, characterized in that, The composition A, by weight, comprises the following components: 10-50 parts of zinc-enriched yeast, 60-190 parts of enzymatically hydrolyzed bone meal, 200-1000 parts of collagen peptides, and 0.5-10 parts of selenium-enriched corydalis leaf extract or 0.0022-0.0438 parts of sodium selenite.

2. The composition A for promoting bone growth in children according to claim 1, characterized in that, By weight, it includes the following components: 22.5-35 parts zinc-enriched yeast, 80-140 parts enzymatically hydrolyzed bone meal, 450-750 parts collagen peptides, and 0.5-2.5 parts selenium-enriched corydalis leaf extract or 0.0022-0.0110 parts sodium selenite.

3. The composition A for promoting bone growth in children according to claim 1 or 2, characterized in that, The chondroitin sulfate content in the enzymatically hydrolyzed bone powder is not less than 80%.

4. The composition A for promoting bone growth in children according to claim 1 or 2, characterized in that, The selenium content in the selenium-enriched corydalis leaf extract is not less than 0.1%.

5. The composition A for promoting bone growth in children according to any one of claims 1-4, characterized in that, The composition A is a powder, granules, tablets, capsules, liquid beverage, or oral liquid; preferably a powder, granules, or tablets.

6. A composition B for promoting bone growth in children, characterized in that, Composition B, by weight, comprises the following components: 10-50 parts of zinc-enriched yeast or 0.25-1.25 parts of zinc oxide, 5-20 parts of γ-aminobutyric acid, and 30-120 parts of L-lysine or isolated whey protein (based on L-lysine content).

7. The composition B for promoting bone growth in children according to claim 6, characterized in that, By weight, it includes the following components: 22.5-35 parts zinc-enriched yeast or 0.563-0.875 parts zinc oxide, 9-15 parts γ-aminobutyric acid, and 45-75 parts L-lysine or whey protein isolate (based on L-lysine content).

8. The composition B for promoting bone growth in children according to claim 6 or 7, characterized in that, The composition B is a powder, granules, tablets, capsules, liquid beverage, or oral liquid; preferably a powder, granules, or tablets.

9. A composition C for promoting bone growth in children, characterized in that, It includes composition A as described in any one of claims 1-5 and composition B as described in any one of claims 6-8.

10. The use of the composition A for promoting bone growth in children according to any one of claims 1-5, the composition B for promoting bone growth in children according to any one of claims 6-8, and the composition C for promoting bone growth in children according to claim 9 in the preparation of food, medicine or health products that promote bone growth in children.

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