Edible and medicinal composite nutritional factor composition with function of improving bone mineral density

Abstract

The invention provides an edible and medicinal composite nutritional factor composition with a function of improving bone mineral density. Through optimization of nutrition composition and proportion and systematic research on verification, the formula which takes eucommia ulmoides and herba epimedii as a conditioning basis and is compounded with calcium carbonate, D-glucosamine hydrochloride, sodium chondroitin sulfate and collagen and has the function of improving bone mineral density is constructed. The whole plant components synergistically play a role in tonifying bones, and nutritional factors such as calcium, collagen and glucosamine complement each other in efficacy to provide nutritional support for bones and joints. Meanwhile, by combining the process design of nano embedding and the like, the preparation method for promoting the absorption of the composition is realized, and the calcium absorption rate and the bone calcium content can be improved. Animal safety and function experiments prove that the health-care food is a safe and non-toxic product capable of improving bone mineral density, and is used for strengthening waist and knees, strengthening muscles and bones, supplementing calcium, improving osteoporosis, protecting joints, relieving joint stiffness and pain and the like.

Description

Technical Field

[0001] This invention belongs to the field of bone and joint health care technology, specifically a food and medicine homologous compound nutritional factor composition with the function of improving bone density. Clinically, it is used to improve bone density, improve osteoporosis, repair joint damage, and relieve joint stiffness and pain. Background Technology

[0002] Osteoarthritis is a relatively common clinical disease. Its occurrence is related to a variety of factors such as age, bone density, estrogen levels, joint damage, and high labor intensity. It usually has a higher incidence in middle-aged and elderly people and generally manifests as a series of biochemical and morphological changes such as joint erosion, bone hyperplasia, and cartilage sclerosis, such as osteoporosis, rickets, and arthritis.

[0003] Osteoporosis is a systemic musculoskeletal disease characterized by decreased bone mass and deterioration of bone microstructure. Its features include reduced bone density and bone microstructure deterioration, leading to a significantly increased risk of fractures and gradually evolving into a global public health problem. In my country, with the increasing aging of the population, the number of people suffering from osteoporosis is also constantly increasing. Osteoporosis not only affects the normal quality of life of patients but also has a significant impact on the psychological and economic well-being of patients and their families. Studies have found that factors influencing osteoporosis include genetics, endocrine function, dietary habits, and living environment. According to the 2018 "China Osteoporosis Epidemiological Survey," the prevalence rate in people over 65 years of age was 32%, with a rate as high as 51.6% in women, and a low bone rate of 46.4%. Surveys have revealed that the number of people suffering from osteoporosis worldwide has reached approximately 200 million in recent years, and is projected to exceed 300 million by 2030. Currently, 70-80 million people in my country suffer from osteoporosis, with a prevalence rate as high as 56% in those over 60 years of age. With the increasing aging population, the prevalence rate in my country will continue to rise, seriously threatening people's normal lives and mental health. Osteoporosis is a systemic skeletal disease characterized by changes in the microstructure of bone tissue, accompanied by increased bone fragility and a heightened risk of fracture. In osteoporosis, bone loss is characterized by a decrease in the ratio of bone minerals to bone matrix. This loss is detected through imaging and bone morphometric examinations, manifesting as decreased bone density, making fractures possible even with minor external forces.

[0004] Osteoarthritis, also known as osteoarthritis, degenerative arthritis, or senile arthritis, is a common orthopedic disease. It is characterized by progressive wear and tear and destruction of articular cartilage, clinically manifesting as slowly developing joint pain, tenderness, stiffness, swelling, limited range of motion, and joint deformities. It can even lead to knee joint dysfunction, affecting a person's ability to move freely. It most commonly affects the knee, hip, spine, and hand joints. In 1999, the World Health Organization listed osteoarthritis as one of the three major diseases threatening human health. WHO statistics show that the incidence of osteoarthritis is 50% in people over 50 years of age and 80% in those over 55 years of age. Clinical surveys also confirm that the incidence of osteoarthritis is 29% between 59 and 69 years of age, and approximately 70% in those 75 years of age or older. Many factors contribute to osteoarthritis, including a history of joint injury or overuse, advanced age, and being overweight.

[0005] Currently, most bone and joint health products on the market are nutrient supplements. These products mainly supplement minerals and vitamins such as calcium and vitamin D, primarily strengthening bones by replenishing minerals lost from the bones. However, they suffer from limitations due to their single-ingredient formulation and unsatisfactory effects. A smaller number of products use compound ingredients (calcium, glucosamine salts, chondroitin sulfate, etc.) to supplement nutrients from multiple angles and repair bones and joints. While these products offer some supplementation, they are often limited to a simple addition of ingredients and still suffer from poor efficacy or short-lasting effects. They cannot fundamentally improve bone quality and achieve long-term improvements in bone strength and quality, or reduce recurrence.

[0006] The composition provided by this invention, from a nutritional perspective, uses calcium carbonate to supplement calcium while simultaneously supplementing collagen, improving bone toughness and binding calcium to further increase bone density; sodium chondroitin sulfate promotes osteoblast proliferation, improves osteoporosis, and combines with collagen to produce a high-molecular-weight fixed structure, improving bone quality; D-glucosamine hydrochloride stimulates glycoprotein production, relieves joint inflammation and pain, and synergistically improves bone density with sodium chondroitin sulfate; icariin promotes osteoblast proliferation and activity, working synergistically with sodium chondroitin sulfate. From the perspective of traditional Chinese medicine theory, epimedium is pungent, sweet, and warm. It enters the liver and kidney meridians. It tonifies kidney yang and strengthens tendons and bones. It is used for kidney yang deficiency and weakness of tendons and bones; eucommia is sweet and warm. It enters the liver and kidney meridians. It tonifies the liver and kidneys and strengthens tendons and bones. It is used for liver and kidney deficiency, lower back and knee pain, and weakness of tendons and bones. The combination of the two, with the fundamental goal of regulating the liver and kidneys, can enhance liver and kidney yang, thereby strengthening the lower back and knees and fortifying tendons and bones through tonifying the liver and kidneys. This invention addresses both the symptoms and the root cause, strengthening the body, nourishing bones, and fortifying muscles and bones. Therefore, it not only improves bone density, repairs joint damage, and relieves joint stiffness, pain, and discomfort, but also fundamentally stimulates bone cell proliferation and activity, synergistically improving bone quality, promoting the synthesis and secretion of bone matrix, strengthening bones, and combating osteoporosis and joint damage.

[0007] Whole-plant is generally defined as a plant that has undergone minimal processing and is close to its original state, retaining its natural and more complete characteristics. Single supplements (such as vitamin C tablets, vitamin E capsules, calcium tablets, etc.) are designed to provide one or more specific nutrients. While the latter are often used to treat specific deficiencies or in certain medical situations, whole-plant has an overwhelming advantage for daily prevention and overall health. Whole-plant is a holistic concept of nutritional activity; the active ingredients exist in their natural forms and proportions, and the various antioxidants and phytochemicals within them do not exist in isolation; they work synergistically to produce a "1+1>2" effect. Supplements, on the other hand, are isolated, single nutrients that cannot replicate this complex natural synergistic effect.

[0008] Epimedium and Eucommia are key herbs in Traditional Chinese Medicine for tonifying kidney yang and strengthening tendons and bones, containing hundreds of active ingredients. For example, modern research shows that Epimedium, through at least 27 major active ingredients (such as the flavonoid compound icariin), regulates multiple key pathways including bone metabolism, lipid metabolism, nitrogen metabolism, and GABAergic synapses, thus exerting therapeutic effects on 11 types of orthopedic diseases, including osteoarthritis (OA) and osteoporosis (OP). Epimedium has diverse active ingredients; for example, flavonoid glycosides can reduce chondrocyte apoptosis, icariin can promote osteogenic differentiation and inhibit osteoclast resorption after metabolism, alkaloids can relieve joint swelling, and polysaccharides can reduce systemic inflammation and promote bone formation through immune regulation. It is through the synergistic effect of multiple components and multiple targets that it is applied to orthopedic treatment. Currently, most Epimedium extracts on the market are obtained through water or alcohol extraction, or further purified using macroporous resins and membranes to enrich certain active ingredients. For example, extracts of Epimedium rich in flavonoids or polysaccharides are completely disconnected from their functional applications, failing to meet real market demands and limiting their applicability. Therefore, the search for and promotion of technologies and applications for Epimedium extracts rich in multiple active ingredients and in a near-original state—that is, whole Epimedium plant extracts—is urgently needed. On the other hand, components in Epimedium extracts, such as flavonoids, have highly hydrophobic aglycone molecules and poor water solubility, resulting in very low dissolved amounts in the gastrointestinal tract and extremely low absorption rates (usually below 5%), affecting the efficacy of the final product. Therefore, technological improvements are needed to enhance their water solubility, increase effective absorption rates, and thus fully realize their efficacy.

[0009] In summary, bone and osteoarthritis are facing a severe development trend. Their difficulty in detection and their insidious nature exacerbate the severity of the problem. People not only miss the optimal time for intervention and repair but also have to endure the torment of disease pain, leading to a precipitous decline in quality of life and a surge in treatment costs. Commercially available health products of this type are mostly made by simply adding various nutrients, with limited or unsustainable effects. There is an urgent need for a more effective bone health product that can fundamentally improve bone quality. This invention utilizes a compound nutritional factor derived from both food and medicine, focusing on regulating the liver and kidneys, strengthening the waist and knees, and fortifying muscles and bones. It aims to provide nutritional support for bones and joints, promote growth and repair, and synergistically improve bone quality, combating osteoporosis and joint damage. Through a special preparation process, it obtains all-plant ingredients, fully leveraging their natural synergistic effects to stimulate bone cell proliferation and enhance bone cell activity from within. To overcome the problems of poor water solubility and low bioavailability of active ingredients in Epimedium, such as flavonoids, a collagen nano-encapsulation technology is used to modify solubility, increase absorption, and better exert a synergistic effect. This allows the product to improve calcium absorption and increase bone calcium content. The product of this invention has a specific function of improving bone density and is used to improve osteoporosis, protect joints, and relieve joint stiffness and pain. Summary of the Invention

[0010] The purpose of this invention is to provide a food-medicine homologous compound nutritional factor composition with bone density-improving function, thereby solving the problems existing in the background art. The composition, through the combination of food-medicine homologous and nutritional factors, not only precisely strengthens bone and joint nutrition, improves bone hardness and toughness, and improves the inflammatory environment of joints, but also regulates the liver and kidneys, stimulates liver and kidney yang to strengthen tendons and bones, fundamentally stimulates bone cell proliferation, improves bone cell activity, and improves bone quality. When used in combination, it treats both the symptoms and the root cause, enabling long-term health management and reducing recurrence, with a more sustained effect. The whole plant extract of Epimedium fully retains the complete active ingredients, existing in their natural form and proportion, synergistically promoting bone proliferation and bone mineral deposition at multiple targets, thus exerting a health-promoting effect on improving bone density. To further improve the bioavailability of the whole plant, considering the poor water solubility of Epimedium's active ingredients, a nano-encapsulation process is used to promote the absorption of active ingredients, increase calcium absorption rate and bone calcium content, and maximize biological efficacy. Animal safety toxicology experiments have proven that the product is non-toxic, has no genotoxicity, and is safe for consumption. Animal functional experiments have proven that it can improve bone density and is used for bone function maintenance and enhancement, such as strengthening the waist and knees, strengthening muscles and bones, supplementing calcium, improving osteoporosis, protecting joints, and relieving joint stiffness and pain. To achieve the above objectives, this invention provides the following technical solution: This invention provides a food-medicine homologous compound nutritional factor composition with bone density-improving function, comprising the following components in parts by weight: 20-40 parts calcium carbonate, 10-30 parts D-glucosamine hydrochloride, 10-30 parts chondroitin sulfate sodium, 5-25 parts collagen, 4-12 parts epimedium extract, 4-12 parts eucommia extract, 6-30 parts microcrystalline cellulose, and 0.4-1.2 parts magnesium stearate. The collagen is composed of 14-25 amino acids (typically, the proportion with a molecular weight between 1000-3000 Daltons is higher than 85%) and encapsulates the epimedium extract, which is obtained through processes such as salting, crushing and filtering, acid precipitation, filtration, concentration, and freeze-drying.

[0011] The composition is a capsule formulation; however, other dosage forms, such as powders or tablets, can also be used. If it is a capsule formulation, the composition further includes the following components in parts by weight: 6-30 parts microcrystalline cellulose and 0.4-1.2 parts magnesium stearate. The preparation method of the capsule formulation is as follows: According to the specified proportions, calcium carbonate, D-glucosamine hydrochloride, chondroitin sulfate sodium, Eucommia ulmoides extract, microcrystalline cellulose, and collagen-encapsulated Epimedium extract nanoparticles are mixed evenly in a multi-directional motion mixer (mixing speed 4-12 r / min, mixing time 20-40 min). Using 65-85% edible alcohol (volume concentration) as a wetting agent, wet granules are prepared using a 16-40 mesh screen and then dried in a forced-air drying oven until the moisture content is ≤5% (drying temperature 45-60℃, drying time 1.0-3.0 h). A lubricant, magnesium stearate, is added to the above granules and mixed evenly in a multi-directional motion mixer (mixing speed 6-10 r / min, mixing time 5-8 min). The mixture is then filled using a capsule filling machine (0.5 g / capsule) and packaged to obtain the final product.

[0012] Preferably, the food and medicine homologous compound nutritional factor composition with bone density improvement function provided in the embodiments of the present invention comprises the following components in parts by weight: 20-40 parts of calcium carbonate, 15-30 parts of D-glucosamine hydrochloride, 15-25 parts of chondroitin sulfate sodium, 10-20 parts of collagen, 5-10 parts of epimedium extract, 6-10 parts of eucommia extract, 8-25 parts of microcrystalline cellulose, and 0.5-1.0 parts of magnesium stearate.

[0013] More preferably, the food and medicine homologous compound nutritional factor composition with bone density improvement function provided in the embodiments of the present invention includes the following components in parts by weight: 30 parts calcium carbonate, 20 parts D-glucosamine hydrochloride, 20 parts sodium chondroitin sulfate, 15 parts collagen, 8 parts epimedium extract, 8 parts eucommia extract, 18 parts microcrystalline cellulose and 0.8 parts magnesium stearate.

[0014] Among them, the proportion of Gly-XY repeat sequences in collagen is 40-46%. That is, under the premise of specific structure (Gly-XY repeat sequence proportion of 40-46%) and specific molecular weight (the proportion of molecular weight between 1000-3000 Daltons is higher than 85%), this patent has better encapsulation effect, the encapsulated material has better water solubility, and can better improve the product effect.

[0015] Eucommia ulmoides extract is an alcohol extract, which can be purchased commercially or prepared at home. The preparation process of Eucommia ulmoides extract as an alcohol extract is as follows: Eucommia ulmoides fragments and 60-70% ethanol (volume concentration) are added to an ultrasonic extraction vessel at a material-to-liquid ratio of 1:16-18 (mass ratio of Eucommia ulmoides fragments to ethanol). The water bath temperature is set to 45-60℃, the ultrasonic power to 300-400W, and the ultrasonic frequency to 30-40kHz. Extraction is carried out for 45-55 minutes. Ultrasonic extraction allows for extraction at low temperatures, ensuring efficacy.

[0016] The process of encapsulating Epimedium extract with collagen is as follows: Collagen is dissolved in water at 30-40℃ to obtain a collagen aqueous solution, with a water-to-collagen mass ratio of 4-10:1 (specifically, 6:1). Epimedium extract is dissolved in acetone to obtain an Epimedium-acetone solution, with an acetone-to-epimedium extract mass ratio of 8-15:1 (specifically, 10:1). The collagen aqueous solution and Epimedium-acetone solution are fed into a high-speed shear mill for mixing according to the specified ratio. After mixing, the solvent is evaporated to obtain encapsulated particles.

[0017] Specifically, the mixing process of the high-speed shearing machine is as follows: process at 6000-10000 rpm (specifically 8000 rpm) for 2-5 minutes, and then process at 18000-25000 rpm (specifically 20000 rpm) for 8-10 minutes.

[0018] Specifically, the process of evaporating the solvent to obtain the embedded particles is as follows: the embedded particles are obtained by rotary evaporation at 35-42℃.

[0019] The source of Epimedium extract is as follows: Salt is added to fresh Epimedium, mixed thoroughly, and salted for 2-4 hours. The amount of salt added is 5-8% of the weight of the fresh Epimedium. The salted Epimedium is then fed into a pulper, and 2-4 times its volume (specifically 3 times) of water is added. The pulping process takes 10-15 minutes, and the pulp is filtered through a 150-250 mesh (specifically 200 mesh) sieve. A 5-8 g / L citric acid aqueous solution (1:10-25 volume ratio of citric acid aqueous solution to filtered pulp) is slowly added to the filtered pulp while stirring, adjusting the pH to 5.6-6.0. The mixture is then allowed to settle overnight. After centrifuging the settled liquid (specifically, at 5000 rpm for 15 minutes), filter (specifically, through a 200-mesh filter), and concentrate (specifically, by rotary evaporation at 45-50°C) to a solid content of 60-75%; finally, freeze-dry to obtain the Epimedium extract. The freeze-drying conditions are: pre-freezing at -40 to -15°C for 6-10 hours, followed by vacuum drying at 5-30°C under a vacuum of 0.2-0.3 MPa for 4-6 hours. The freeze-dried extract is then pulverized.

[0020] Preferably, the Epimedium in this patent is Korean Epimedium.

[0021] Compared with the prior art, the beneficial effects of the present invention are: 1. The composition of this invention is rich in various essential amino acids, chondroitin sulfate, calcium, collagen, etc., which can meet people's nutritional needs. Calcium carbonate is a cost-effective and efficient exogenous calcium preparation. D-glucosamine hydrochloride, as a chitin-like substance, can repair damaged articular cartilage, protect joints, and promote the absorption and utilization of calcium by bones. Chondroitin sulfate can form a macromolecule with collagen, promoting bone formation, protecting articular cartilage, and resisting arthritis, thereby increasing bone density and improving osteoporosis. Epimedium enters the liver and kidney meridians and can tonify kidney yang, strengthen tendons and bones, and dispel wind and dampness. Modern medical research shows that Epimedium has a proliferative effect on osteoblasts, increasing their activity while promoting osteoblast proliferation, thus helping to increase bone density. Eucommia ulmoides tonifies the liver and kidneys, strengthens tendons and bones, and can be used for symptoms such as liver and kidney deficiency, lower back and knee pain, and weakness of tendons and bones. Modern medical research shows that Eucommia ulmoides can promote the deposition of bone minerals, promote the healing of traumatic fractures, and help increase bone density. Through a scientific and rational extraction process, Epimedium further optimizes its active ingredients, which work synergistically with calcium carbonate, D-glucosamine hydrochloride, chondroitin sulfate, collagen, and other components to exert its health benefits of increasing bone density.

[0022] 2. Nano-encapsulation technology not only improves the water solubility and bioavailability of Epimedium extract, but also allows for greater absorption in the intestines. The nanoscale particles possess better adhesion, enabling them to remain on the intestinal mucosa for a longer period, thus extending the absorption window. Currently, the active ingredients in Epimedium extracts generally have poor solubility and extremely low absorption rates (typically below 5%), which is a major bottleneck restricting their bioavailability and product development. Through nano-encapsulation, collagen peptides can form a structure with an external hydrophilic and internal hydrophobic cavity, binding with icariin and other components through various non-covalent bonds to form a stable complex. Flavonoids and aglycones that are originally insoluble in water are encapsulated within the hydrophobic core of the collagen nanoparticles. The entire nanoparticle becomes easily dispersed in water due to the external hydrophilic peptides, thereby significantly improving solubility.

[0023] 3. Complete proteins have complex structures, significant steric hindrance, and limited ability to interact with hydrophobic molecules. Collagen is a polypeptide, with peptide chains typically composed of 14-25 amino acids, and its unique Gly-XY repeat sequence accounts for 40-46%. This characteristic of collagen oligopeptides, with peptide chains composed of 14-25 amino acids, avoids the problem of being too short to form a stable structure, ensuring structural controllability and solubility. It also avoids the problem of being too long to control self-assembly and cause encapsulation failure. The Gly-XY repeat sequence contains a large number of hydrophilic amino acids, which can form hydrogen bonds with water, constituting the shell of nanoparticles and ensuring water solubility and biocompatibility. The 40-46% ratio, a balance between hydrophilic and hydrophobic components, facilitates the formation of regular nanostructures. This allows peptide segments to spontaneously aggregate in aqueous solutions, with the hydrophobic ends facing inward and the hydrophilic ends facing outward, forming a spherical structure called a "nanoparticle." This hydrophobic internal cavity is the perfect place to encapsulate the hydrophobic molecules of Epimedium extract.

[0024] 4. Collagen is mostly composed of 14-25 amino acids. This short molecular weight peptide avoids complete breakdown by gastric acid and pepsin, yet is large enough to maintain the integrity of its bioactive sequence, allowing it to pass directly through the peptide transport system of small intestinal epithelial cells, resulting in high bioavailability. It can be directly absorbed into the bloodstream in its complete short peptide form, exerting its core function as a bioactive signaling molecule. Its unique Gly-XY repeating functional sequence is recognized by receptors on the surface of osteoblasts in bone tissue, opening signaling pathways and stimulating the synthesis of new collagen and the proliferation of bone cells. Compared to simply supplementing amino acids, this "signal transduction" mechanism is much more efficient, directly regulating the root causes of collagen and bone metabolism. The unique Gly-XY repeating functional sequence also has chemotaxis, promoting the targeted action of collagen peptides and more precisely promoting bone collagen synthesis and bone cell metabolism.

[0025] 5. The Epimedium extract of this invention is derived from the whole plant Epimedium, unlike existing Epimedium extracts which only contain a single active component. This invention provides all the main active components of Epimedium. Epimedium tonifies kidney yang, ensuring sufficient kidney essence and generating marrow, thus strengthening bones. It holistically improves the body's energy metabolism, endocrine function, and overall functional state, creating the most favorable environment for bone repair. Regarding bones, flavonoids such as icariin can activate signaling pathways such as Wnt / β-catenin in bone cells, promoting new bone formation, while blocking the RANKL / RANK signaling pathway and inhibiting osteoclast resorption. Epimedium polysaccharides can regulate the function of immune cells such as macrophages, creating a favorable environment for bone repair. Regarding joints, flavonoids downregulate COX-2 and iNOS expression, inhibiting inflammation; polysaccharides regulate immunity and antioxidation, reducing oxidative stress damage to articular cartilage. By directly regulating bone and chondrocytes through flavonoids and indirectly supporting the immune microenvironment by improving polysaccharides, it not only targets the metabolic balance of bones but also the inflammation of joints and cartilage damage. The synergistic effect of multiple components and multiple targets produces a 1+1>2 effect, which directly intervenes in the local pathological changes of bones and joints (treating the symptoms) and improves the overall functional state of the body by tonifying the kidneys (treating the root cause), thus achieving the overall bone health effect.

[0026] 6. The entire process of preparing Epimedium in this invention is carried out at a temperature of <50℃, which can preserve its original chemical components to the greatest extent. Existing Epimedium extraction techniques mostly use water or alcohol extraction and hot air circulation drying at a temperature of 80-100℃ for 2-8 hours. Prolonged and continuous heating of Epimedium causes instability of the effective components, leading to degradation or transformation. This invention avoids the significant decrease and hydrolysis of the effective components of Epimedium.

[0027] 7. In the preparation method of Epimedium extract, the semi-permeability of plant cells is destroyed by salting, the cell walls collapse, and the leaf tissue softens, which is conducive to the next step of pulping and crushing; it can inhibit the activity of polyphenol oxidase, prevent leaf discoloration (such as browning), and protect the activity of raw materials. Meanwhile, a certain concentration of salt ions in the slurry makes the subsequent precipitation process easier and more complete, because salt ions can neutralize the charge on the surface of proteins and weaken the electrostatic repulsion between protein molecules, thus making it easier for them to aggregate and precipitate at the isoelectric point.

[0028] 8. In the preparation method of Epimedium extract, precipitation with citric acid water is used to specifically remove inactive plant proteins while maximally retaining the main active ingredients such as flavonoids, polysaccharides, and alkaloids, thus maximizing their synergistic effects across multiple components and targets. Citric acid water provides a pH of 5.6-6.0 for the slurry, at which point the plant proteins in Epimedium reach their isoelectric point, causing them to denature and precipitate. The main active ingredients, such as flavonoid glycosides, flavonoid aglycones, polysaccharides, and alkaloids, exhibit better structural stability in this weakly acidic environment, preventing the breakage of glycosidic bonds and hydrolysis degradation in strong acid or alkaline environments, thus avoiding a decrease in the content of active ingredients.

[0029] 9. The preferred source of Epimedium is *Epimedium koreanum*. Other suitable sources include *Epimedium pubescens*, *Epimedium koreanum*, and *Epimedium sagittatum*. *Epimedium koreanum* has relatively large leaflets, 4-10 cm long and 3.5-7 cm wide, and the leaves are thinner. Traditionally, harvesting and processing involves sun-drying or air-drying, moistening with water before use, shredding, and drying again—a cumbersome process. In this invention, the thin leaves of *Epimedium koreanum* provide a larger surface area for salting and crushing, allowing for easier and more complete exudation of the tissue contents, thus providing a high-quality starting material for subsequent preparation and processing.

[0030] 10. The Eucommia ulmoides extract in this invention is obtained through a combined ultrasonic-ethanol extraction process. Eucommia ulmoides contains a complex composition, including water-soluble components such as polysaccharides and aucubin, as well as alcohol-soluble components such as chlorogenic acid, flavonoids, and iridoid glycosides. It also contains Eucommia gum, which has low solubility in conventional solvents. Using a single solvent makes it difficult to obtain a comprehensive range of original active ingredients. Furthermore, water and alcohol extractions involve high temperatures and long extraction times (2-4 hours), easily leading to component decomposition, such as the thermal instability and decomposition of chlorogenic acid and the enzymatic degradation of aucubin. However, in the combined ultrasonic-ethanol extraction process, the propagation of ultrasound in the ethanol solvent generates countless tiny, rapidly forming and collapsing "bubbles" (cavitation bubbles). At the moment of collapse, these bubbles generate a high pressure of several thousand atmospheres within a very small space. On the one hand, the enormous pressure shock wave can instantly shatter the cell walls of Eucommia ulmoides, directly exposing the active ingredients within the cells to the solvent. On the other hand, it greatly enhances the rate and efficiency of solvent penetration into the cells and component diffusion into the solvent. Not only can it break through the limitations of traditional application of the principle of like dissolves like to obtain effective ingredients, but it also uses ultrasonic cavitation effect to dissolve the effective ingredients. Furthermore, the entire process is short in time and low in temperature, which can maximize the retention of effective ingredients, save energy, and improve efficiency.

[0031] 11. Synergistic Effect of Formula Ingredients: Combining Traditional Chinese and Western Medicine, Treating Both Symptoms and Root Causes. From a modern medical perspective, calcium carbonate provides a calcium source for bones, maintaining bone integrity and strength, and improving bone density; collagen assists in promoting calcium absorption and forms a network structure, promoting calcium deposition and bone formation, improving bone density, and enhancing bone hardness and toughness; D-glucosamine hydrochloride + chondroitin sulfate improve the inflammatory microenvironment, regulate the activity of osteoclasts and osteoblasts, inhibit bone resorption, promote bone formation, improve the bone marrow microenvironment, maintain the dynamic balance of bone metabolism, and improve bone density. From the perspective of traditional Chinese medicine theory, Eucommia ulmoides: sweet and warm. Enters the liver and kidney meridians. Tonifies the liver and kidneys, strengthens tendons and bones, used for liver and kidney deficiency, lower back and knee pain, and weakness of tendons and bones. Epimedium: pungent, sweet, and warm. Enters the liver and kidney meridians. Tonifies kidney yang and strengthens tendons and bones. Used for kidney yang deficiency, weakness of tendons and bones, rheumatic pain, numbness and contracture. When used together, the two can strengthen the liver and kidneys, improve liver and kidney deficiency, and strengthen muscles and bones. They are used for symptoms such as lower back and knee pain and weakness of muscles and bones caused by liver and kidney deficiency. Detailed Implementation

[0032] To further illustrate the present invention, the following detailed description of the embodiments is provided in conjunction with the present invention, but these descriptions should not be construed as limiting the scope of protection of the present invention.

[0033] Example 1 Example 1 provides a food-medicine homologous compound nutritional factor composition with bone density improvement function, comprising the following parts by weight: 30 parts calcium carbonate, 20 parts D-glucosamine hydrochloride, 20 parts chondroitin sulfate sodium, 15 parts collagen, 8 parts epimedium extract, 8 parts eucommia extract, 18 parts microcrystalline cellulose, and 0.8 parts magnesium stearate. The preparation steps are as follows: Preparation of Epimedium extract: (1) Take freshly harvested Korean Epimedium, wash it clean and drain the water; add edible salt at a weight percentage of 6%, mix it evenly with a fork, and marinate for 3 hours.

[0034] (2) Using a pulping machine, add the salted Epimedium (including the bottom juice), add 2.2 times the volume of water, pulp, and crush for 12 minutes; the pulp is then passed through a 200-mesh sieve.

[0035] (3) Prepare a 6 g / L citric acid aqueous solution and slowly add it to the filtered slurry while stirring to make the pH 5.8. Let it stand overnight to settle. Centrifuge at 5000 rpm for 15 minutes. Filter the supernatant through a 200 mesh sieve.

[0036] (4) Concentrate by rotary evaporation at 50°C until the solid content is 70%.

[0037] (5) Use a freeze dryer to pre-freeze at -40 to -15℃ for 8 hours, then vacuum dry at 5-30℃ with a vacuum degree of 0.2-0.3MPa for 5 hours; then pulverize into fine powder using a multi-functional pulverizer.

[0038] Preparation of Eucommia ulmoides extract: (1) Take Eucommia ulmoides fragments and put them into an ultrasonic extraction tank. Add 60% (volume concentration, the same below) ethanol at a material-to-liquid ratio of 1:16. Set the temperature of the water bath jacket to 45℃, the ultrasonic power to 300W, the ultrasonic frequency to 40kHz, and extract for 50 minutes.

[0039] (2) The solid-liquid mixture is obtained by solid-liquid separation, concentration and spray drying.

[0040] Preparation of the composition: (1) Nano-encapsulation: Collagen was dissolved in water at 35°C (weight ratio 1:5), and Epimedium extract was added to acetone (weight ratio 1:10) and stirred. The two were then mixed in a high-shear mixer (stage shearing mode: first stage speed 8000 rpm, time 4 minutes; second stage speed 23000 rpm, time 8 minutes). The mixture was then evaporated by rotary evaporation (40°C) to obtain nano-encapsulated particles.

[0041] (2) Take calcium carbonate, D-glucosamine hydrochloride, chondroitin sulfate sodium, Eucommia ulmoides extract, and microcrystalline cellulose according to the specified ratio. Mix the nano-encapsulated particles obtained above evenly in a multi-directional motion mixer (mixing speed 8 r / min, mixing time 30 min). Use 80% edible alcohol (volume concentration, the same below) as a wetting agent and 16-40 mesh wet granules.

[0042] (3) Dry in a forced-air drying oven until the moisture content is ≤5% (drying temperature is 50℃, drying time is 2.0h).

[0043] (4) Add magnesium stearate to the above particles and mix them evenly in a multi-directional motion mixer (mixing speed is 8 r / min, mixing time is 6 min).

[0044] (5) Fill the capsules using a capsule filling machine (0.5g / capsule), and then package them.

[0045] Example 2 Example 2 provides a food-medicine homologous compound nutritional factor composition with bone density improvement function, comprising the following parts by weight: 20 parts calcium carbonate, 30 parts D-glucosamine hydrochloride, 15 parts chondroitin sulfate sodium, 20 parts collagen, 5 parts epimedium extract, 6 parts eucommia extract, 25 parts microcrystalline cellulose, and 0.5 parts magnesium stearate. The preparation steps are as follows: Preparation of Epimedium extract: (1) Take freshly harvested Korean Epimedium, wash it clean and drain the water; add edible salt at a weight percentage of 6%, mix it evenly with a fork, and salt it for 4 hours.

[0046] (2) Using a pulping machine, put in the salted Epimedium (including the bottom juice), add 3 times the volume of water, pulp, and crush for 10 minutes; the pulp is then passed through a 200-mesh sieve.

[0047] (3) Prepare an 8 g / L citric acid aqueous solution and slowly add it to the filtered slurry while stirring to make the pH 5.6. Let it stand overnight to settle. Centrifuge at 5000 rpm for 15 minutes. Filter the supernatant through a 200 mesh sieve.

[0048] (4) Concentrate by rotary evaporation at 50°C until the solid content is 70%.

[0049] (5) Use a freeze dryer to pre-freeze at -40 to -15℃ for 6 hours, then vacuum dry at 5-30℃ with a vacuum degree of 0.2-0.3MPa for 4 hours; then pulverize into fine powder using a multi-functional pulverizer.

[0050] Preparation of Eucommia ulmoides extract: (1) Take Eucommia ulmoides fragments and put them into an ultrasonic extraction tank. Add 70% ethanol at a material-to-liquid ratio of 1:16. Set the temperature of the water bath jacket to 50℃, the ultrasonic power to 400W, the ultrasonic frequency to 30kHz, and extract for 55 minutes.

[0051] (2) The solid-liquid mixture is obtained by solid-liquid separation, concentration and spray drying.

[0052] Preparation of the composition: (1) Nano-encapsulation: Collagen was dissolved in water at 40°C (weight ratio 1:6), and Epimedium extract was added to acetone (weight ratio 1:8) and stirred. The two were then mixed in a high-shear mixer (stage shearing method: first stage speed 6000 rpm, time 2 minutes; second stage speed 20000 rpm, time 10 minutes). The mixture was then evaporated by rotary evaporation (40°C) to obtain nano-encapsulated particles.

[0053] (2) Take calcium carbonate, D-glucosamine hydrochloride, chondroitin sulfate sodium, eucommia extract, and microcrystalline cellulose according to the specified ratio. Mix the nano-encapsulated particles obtained above evenly in a multi-directional motion mixer (mixing speed 5 r / min, mixing time 40 min). Use 80% edible alcohol as a wetting agent and 16-40 mesh to make wet granules.

[0054] (3) Dry in a forced-air drying oven until the moisture content is ≤5% (drying temperature is 60℃, drying time is 1.5h).

[0055] (4) Add magnesium stearate to the above particles and mix them evenly in a multi-directional motion mixer (mixing speed is 10 r / min, mixing time is 5 min).

[0056] (5) Fill the capsules using a capsule filling machine (0.5g / capsule), and then package them.

[0057] Example 3 Example 3 provides a food-medicine homologous compound nutritional factor composition with bone density improvement function, comprising the following parts by weight: 40 parts calcium carbonate, 15 parts D-glucosamine hydrochloride, 25 parts chondroitin sulfate sodium, 10 parts collagen, 10 parts epimedium extract, 10 parts eucommia extract, 8 parts microcrystalline cellulose, and 1.0 part magnesium stearate. The preparation steps are as follows: Preparation of Epimedium extract: (1) Take freshly harvested Korean Epimedium, wash it clean and drain the water; add edible salt at 8% by weight, mix it evenly with a fork, and salt it for 2 hours.

[0058] (2) Using a pulping machine, put in the salted Epimedium (including the bottom juice), add 4 times the volume of water, pulp, and crush for 15 minutes; the pulp is then passed through a 200-mesh sieve.

[0059] (3) Prepare a 5 g / L citric acid aqueous solution and slowly add it to the filtered slurry while stirring to make the pH 5.9. Let it stand and precipitate overnight. Centrifuge at 5000 rpm for 15 minutes. Filter the supernatant through a 200 mesh sieve.

[0060] (4) Concentrate by rotary evaporation at 50℃ until the solid content is 75%.

[0061] (5) Use a freeze dryer to pre-freeze at -40 to -15℃ for 10 hours, then vacuum dry at 5 to 30℃ with a vacuum degree of 0.2 to 0.3 MPa for 6 hours; then pulverize into fine powder using a multi-functional pulverizer.

[0062] Preparation of Eucommia ulmoides extract: (1) Take Eucommia ulmoides fragments and put them into an ultrasonic extraction tank. Add 60% ethanol at a material-to-liquid ratio of 1:18. Set the temperature of the water bath jacket to 55℃, the ultrasonic power to 400W, the ultrasonic frequency to 40kHz, and extract for 50 minutes.

[0063] (2) The solid-liquid mixture is obtained by solid-liquid separation, concentration and spray drying.

[0064] Preparation of the composition: (1) Nano-encapsulation: Collagen was dissolved in water at 30°C (weight ratio 1:8), and Epimedium extract was added to acetone (weight ratio 1:13) and stirred. The two were then mixed in a high-shear mixer (stage shearing method: first stage speed 10000 rpm, time 5 minutes; second stage speed 18000 rpm, time 9 minutes). The mixture was then evaporated by rotary evaporation (40°C) to obtain nano-encapsulated particles.

[0065] (2) Take calcium carbonate, D-glucosamine hydrochloride, chondroitin sulfate sodium, eucommia extract, and microcrystalline cellulose according to the formula. Mix the nano-encapsulated particles obtained above evenly in a multi-directional motion mixer (mixing speed is 10 r / min, mixing time is 30 min). Use 70% edible alcohol as a wetting agent and 16-40 mesh wet granules.

[0066] (3) Dry in a forced-air drying oven until the moisture content is ≤5% (drying temperature is 50℃, drying time is 2.5h).

[0067] (4) Add magnesium stearate to the above particles and mix them evenly in a multi-directional motion mixer (mixing speed is 6 r / min, mixing time is 8 min).

[0068] (5) Fill the capsules using a capsule filling machine (0.5g / capsule), and then package them.

[0069] 1. Acute oral toxicity test Following the method of GB15193.3, the maximum tolerated dosage method was adopted. The test substance of Example 1 was administered to rats and mice by gavage at the maximum gavage volume and the maximum concentration. During the 14-day observation period after gavage, no obvious poisoning symptoms were observed in the animals, and no deaths occurred. The experimental results are shown in Table 1.

[0070] Table 1

[0071] 2. Ames test According to the GB15193.4 method, the number of revertant colonies in each dose group of the sample was more than twice the number of spontaneous revertant colonies, and there was no dose-response relationship.

[0072] 3. Mouse bone marrow polychromatic erythrocyte micronucleus test Referring to the method of GB15193.5, the micronucleus rate of each dose group in Example 1 of this invention was not significantly different from that of the negative control group. Under the toxic dose conditions, this product did not cause bone marrow cytotoxicity. The experimental results are shown in Table 2.

[0073] Table 2

[0074] 4. 30-day feeding trial Following the method of GB15193.22, and using Example 1 of this invention as the test substance, rats were fed for 30 days. The results showed that during the feeding period, all groups of animals exhibited good growth and development, with no abnormal behavior or symptoms of poisoning, and no deaths. Specific experimental results are shown in Table 3 (Organ / body weight ratio results of the 30-day feeding experiment in rats): Table 3

[0075] Animal safety toxicology experiments have proven that the product is non-toxic, has no genotoxicity, and is safe for consumption.

[0076] Effect verification Compared with Example 1, there was no nano-encapsulation process, but everything else was the same as in Example 1. The components were directly mixed and then made into capsules.

[0077] Comparative to Example 2, the specific process of nano-encapsulation is as follows: Using a single-solvent method, collagen was added to acetone (weight-to-volume ratio of 10-15 mg:1 ml), and dissolved by magnetic stirring at 25°C for 4 hours. Then, Epimedium extract was added, and stirring continued for 2 hours until dissolved, yielding a mixture. The mixture was slowly added dropwise to deionized water with continuous stirring to obtain a nano-precipitate. The solvent was removed by rotary evaporation (40°C), and finally, the nano-encapsulated product was obtained by centrifugation and drying. Other steps are the same as in Example 1.

[0078] Compared with Example 3, the proportion of collagen with a molecular weight between 1000-3000 Daltons was higher than 85%, but the proportion of the unique Gly-XY repeat sequence was less than 30%, and the rest was the same as in Example 1.

[0079] Compared with Example 4, the proportion of collagen with a molecular weight greater than 3000 Daltons was greater than 20%, and the rest was the same as in Example 1.

[0080] Comparative Example 5: The collagen molecular weight is less than 1000 Daltons, and other aspects are the same as in Example 1.

[0081] The encapsulation efficiency was calculated for Examples 1, 3, and Control Examples 1-5. 0.5g of encapsulated particles were placed in a 50ml volumetric flask, and methanol was added to the mark. The absorbance was measured at 270nm using ultraviolet spectrophotometry, following the method for determining the total flavonoid content under the "Epimedium Content Determination" section of the Chinese Pharmacopoeia. Simultaneously, 0.2g of Epimedium extract raw material was weighed and its total flavonoid content was determined. Total flavonoids were calculated as icariin. The experimental results are shown in Table 4.

[0082] Table 4

[0083] The encapsulation rates of Examples 1 and 3 were higher than those of Control Examples 1-4. Control Example 1 did not employ an encapsulation process. Control Example 2 used a single-solvent method for encapsulation. Because the collagen and epimedium extract, after mixing, may only be adsorbed or encapsulated, they would precipitate together during precipitation without being encapsulated, resulting in a weaker encapsulation effect than the Examples. In the Examples, the interfacial tension between the oil and water phases during emulsification pre-confined the hydrophobic active substances to tiny oil phase droplets, while the collagen wall material was in the aqueous phase and encapsulated the oil droplets. After solvent removal, the active substances were "locked" in a dense "shell" composed of the collagen wall material, resulting in a high encapsulation rate. In Control Example 3, the collagen molecular weight was moderate and could dissolve well in the aqueous phase, but the proportion of Gly-XY repeating sequences was too low, and the proportion of hydrophilic groups was insufficient to form enough hydrogen bonds with water to form the outer shell of the nanoparticles, resulting in a low encapsulation yield and the process results not being fully achieved. In Comparative Examples 4 and 5, the collagen molecules were either too large or too small. The amino acid fragments were either too short to form a stable structure or too long to control self-assembly, resulting in encapsulation failure.

[0084] Comparative Example 6, the Epimedium extract is an alcohol extract, and the extraction method refers to the preparation process of Epimedium extract disclosed in patent application number CN201310173011.5. Other aspects are the same as in Example 1.

[0085] The extract of Eucommia ulmoides in Comparative Example 7 was an alcohol extract. The extraction method was based on the research on the extraction of active components of Eucommia ulmoides and the preparation process of functional products by Gu Nannan et al. The specific extraction conditions were: extraction temperature of 85℃, ethanol volume concentration of 72%, liquid-to-solid ratio of 14 mL / g, and extraction time of 2.4 h. Other conditions were the same as in Example 1.

[0086] Animal experiments were conducted on Examples 1-3 and Control Examples 1, 3, and 6-7, following the method described in Scheme 1 of the "Methods for Functional Testing and Evaluation of Health Foods" for "Helping to Improve Bone Density". The specific procedures and results are as follows: Calcium absorption rate and bone mineral density functional test SPF-grade SD rats, weighing 50-80g and no more than 6 weeks old, were used. Ten animals were divided into seven groups, half male and half female. Examples 1-3 and controls 1, 3, 6-7 were added to the basal diet to ensure that the calcium content of each group's diet was 0.5%. The rats were fed at a daily dose of 0.7g / kg body weight. Body weight was measured once a week during the experiment (after fasting for 12 hours).

[0087] Calcium absorption rate determination Three weeks after feeding, rats were placed in stainless steel metabolic cages for a 3-day calcium metabolism experiment. Feed intake was recorded over the three days, and feces were collected after 72 hours. Atomic absorption spectrometry was used to determine the calcium content in the feed samples and feces. The apparent calcium absorption rate (%) was calculated using the formula: Apparent calcium absorption rate (%) = (Ingested calcium - Fecal calcium) / Ingested calcium * 100%.

[0088] Femoral weight measurement Animals were euthanized after 3 months of feeding, and the right femur was removed and baked in an oven at 105°C for 8 hours until constant weight was achieved. After cooling to room temperature, the dry weight of the bone was measured.

[0089] Femoral bone mineral density measurement Determining the midpoint measurement point of the femur: Measure the entire length of the femur, passing through its midpoint, and draw a straight line along the cross-sectional direction. This is the midpoint measurement point (section). Determining the distal femur measurement point: Determine the measurement point at the lowest edge of the articular groove at the distal femur. Draw a straight line through this point parallel to the midpoint mark mentioned above. This is the distal femur measurement point (section). After calibrating the bone densitometer, measure the bone mineral density at the midpoint and distal femur.

[0090] Determination of bone calcium content Accurately weigh the entire femur after baking to constant weight, and place it in a 150ml Erlenmeyer flask that has been dried and cleaned with hydrochloric acid. Add 15-20ml of a mixture of nitric acid and perchloric acid (4:1 ratio), and heat on a hot plate until it produces white fumes and becomes transparent and colorless. Add a few milliliters of deionized water, boil to remove the remaining acid, and repeat twice. After making up to volume, determine the concentration using an atomic absorption spectrophotometer.

[0091] The results of the calcium absorption rate experiment are as follows: Table 5

[0092] The results of the rat femur weight test are as follows: Table 6

[0093] The results of experiments on femoral bone mineral density and bone calcium content in rats are as follows: Table 7

[0094] Compared with Control Examples 1, 3, and 6-7, Examples 1-3 showed superior results in weight gain, bone weight, calcium absorption rate, bone calcium content, and bone density. Through the process of this invention, Epimedium extract and Eucommia ulmoides extract can better leverage the synergistic effects of whole foods, improving bone function holistically through multiple components and targets, creating a favorable environment for bone growth and repair, and activating multiple signaling pathways to achieve high calcium absorption rate, high bone calcium content, and high bone density, thus promoting healthy bone and joint growth.

[0095] Compared with Example 8, the preparation process of Epimedium extract did not include the salting step, and was otherwise the same as in Example 1.

[0096] Compared with Example 9, the preparation process of Epimedium extract was the same as in Example 1, except that citric acid was replaced with acetic acid.

[0097] Comparative Example 10: The preparation process of Epimedium extract was the same as in Example 1, with a citric acid concentration of 20 g / L.

[0098] Compared with Example 11, the preparation process of Epimedium extract was carried out without the addition of citric acid, and otherwise the same as in Example 3.

[0099] Results of plant protein precipitation experiment Plant protein precipitation was identified and measured in Examples 1, 3, and Control Examples 8-11, respectively.

[0100] Identification of plant protein precipitation: Take 0.01g of precipitated protein in a test tube, add 2ml of purified water, add 5 drops of concentrated nitric acid dropwise, place on a water bath and heat gently for 2 minutes, and see if it turns yellow (the benzene ring amino acids in the plant protein undergo a nitration reaction to form a yellow nitro compound).

[0101] Plant protein ratio calculation: The weight of fresh Epimedium was weighed, the moisture content of the fresh Epimedium was measured, and the weight of the precipitate after centrifugation was calculated. The percentage of precipitated plant protein was then calculated. The results are shown in Table 8. Table 8

[0102] The plant protein precipitation rates in Examples 1 and 3 were superior to those in Control Examples 8-11 because the salt added during the salting process ionizes into salt ions. A certain concentration of salt ions in the slurry neutralizes the charge on the protein surface, weakening the electrostatic repulsion of the protein and making it easier to aggregate and precipitate, thus facilitating and ensuring complete precipitation. Citric acid has a stronger ability to regulate acidity than acetic acid, and its metal ion complexing effect is also superior, resulting in higher precipitation efficiency. Excessively high or low pH levels prevent the isoelectric point of Epimedium plant protein from being reached, leading to precipitation failure.

[0103] Although the above embodiments and comparative examples have provided a detailed description of the present invention, they are only some embodiments and comparative examples of the present invention, and not all embodiments and comparative examples. Other embodiments can be obtained based on these embodiments without creative intent, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A food-medicine homologous compound nutritional factor composition with bone density-improving function, characterized in that, The product comprises the following components in parts by weight: 20-40 parts calcium carbonate, 10-30 parts D-glucosamine hydrochloride, 10-30 parts sodium chondroitin sulfate, 5-25 parts collagen, 4-12 parts epimedium extract, and 4-12 parts eucommia extract. The collagen is composed of 14-25 amino acids and encapsulates the epimedium extract. The epimedium extract is obtained by salting, crushing and filtering, acid precipitation, filtration, concentration, and freeze-drying.

2. The food-medicine homologous compound nutritional factor composition with bone density improvement function according to claim 1, characterized in that, If the composition is a capsule formulation, the composition further includes the following components in parts by weight: 6-30 parts of microcrystalline cellulose and 0.4-1.2 parts of magnesium stearate.

3. The food-medicine homologous compound nutritional factor composition with bone density improvement function according to claim 2, characterized in that, It includes the following components in parts by weight: 20-40 parts calcium carbonate, 15-30 parts D-glucosamine hydrochloride, 15-25 parts sodium chondroitin sulfate, 10-20 parts collagen, 5-10 parts epimedium extract, 6-10 parts eucommia extract, 8-25 parts microcrystalline cellulose, and 0.5-1.0 parts magnesium stearate.

4. The food-medicine homologous compound nutritional factor composition with bone density improvement function according to claim 2, characterized in that, The product comprises the following components in parts by weight: 30 parts calcium carbonate, 20 parts D-glucosamine hydrochloride, 20 parts sodium chondroitin sulfate, 15 parts collagen, 8 parts epimedium extract, 8 parts eucommia extract, 18 parts microcrystalline cellulose, and 0.8 parts magnesium stearate.

5. The food-medicine homologous compound nutritional factor composition with bone density-improving function according to claim 1 or 2, characterized in that, The proportion of Gly-XY repeat sequences in collagen is 40-46%.

6. The food-medicine homologous compound nutritional factor composition with bone density improvement function according to claim 1 or 2, characterized in that, The Eucommia ulmoides extract is an alcohol extract.

7. The food-medicine homologous compound nutritional factor composition with bone density improvement function according to claim 1 or 2, characterized in that, The process of encapsulating Epimedium extract with collagen is as follows: collagen is dissolved in water at 30-40℃ to obtain a collagen aqueous solution, with a water-to-collagen mass ratio of 4-10:1; Epimedium extract is dissolved in acetone to obtain an Epimedium-acetone solution, with an acetone-to-Epimedium extract mass ratio of 8-15:1; the collagen aqueous solution and Epimedium-acetone solution are fed into a high-speed shearing machine for mixing according to the ratio; after mixing, the solvent is evaporated to obtain encapsulated particles.

8. The food-medicine homologous compound nutritional factor composition with bone density improvement function according to claim 7, characterized in that, The mixing process using a high-speed shearing machine is as follows: processing at 6000-10000 rpm for 2-5 minutes, followed by processing at 18000-25000 rpm for 8-10 minutes; the process of evaporating the solvent to obtain the embedded particles is as follows: rotary evaporation at 35-42℃ to obtain the embedded particles.

9. The food-medicine homologous compound nutritional factor composition with bone density improvement function according to claim 1 or 2, characterized in that, The source of the Epimedium extract is as follows: salt is added to fresh Epimedium, stirred evenly, and salted for 2-4 hours. The amount of salt added is 5-8% of the weight of the fresh Epimedium. The salted Epimedium is then fed into a pulping machine, and 2-4 times the volume of water is added. The pulping time is 10-15 minutes, and the pulp is filtered through a 150-250 mesh sieve. A 5-8 g / L citric acid aqueous solution is slowly added to the filtered pulp while stirring, so that the pH is 5.6-6.

0. The mixture is allowed to stand overnight to precipitate. After centrifugation, the mixture is filtered and concentrated to a solid content of 60-75%. Finally, the Epimedium extract is obtained by freeze-drying.

10. The food-medicine homologous compound nutritional factor composition with bone density improvement function according to claim 9, characterized in that, The epimedium mentioned is the Korean epimedium.

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