A collagen peptide composition for improving bone density and preparation method thereof

Abstract

The present invention belongs to the technical field of collagen peptides, and particularly relates to a collagen peptide composition for improving bone density and a preparation method thereof. A mixed seaweed solution is mixed with a collagen peptide solution, calcium chloride, and sodium carbonate, and a bone nutrition complex is formed through coprecipitation and ion exchange reaction. After taking, it will not cause an acute increase in the blood calcium level in the blood; the osteoblast metabolism-promoting microcapsules obtained by vacuum freezing nano spray drying cooperate with bone nutrition nanoparticles to promote the metabolic proliferation ability of osteoblasts, osteocytes, and chondrocytes, inhibit the activity of osteoclasts, and maintain the absorption and deposition of calcium in bones for a long time; the bone nutrition nanoparticles and osteoblast metabolism-promoting microcapsules are uniformly dispersed in a stabilizing, anti-inflammatory, and antibacterial matrix, and the prepared collagen peptide composition for improving bone density has a significant effect on improving bone density, maintains bone density for a long time, is non-irritating, and maintains the stability of blood pressure in the body.

Description

Technical Field

[0001] The present invention belongs to the technical field of collagen peptides, and specifically refers to a collagen peptide composition for improving bone density and a preparation method thereof. Background Art

[0002] Bone density mainly refers to the density of bone mineral content per unit volume of bone, which mainly reflects the toughness of bones. Improving bone density is an important measure to maintain bone health, especially for preventing osteoporosis. According to a study published in the journal Bone, high-intensity strength training such as weightlifting and squats can effectively increase bone density. Ensure that your daily diet contains enough calcium and vitamin D, maintain a moderate amount of sun exposure, reduce the intake of coffee, strong tea and carbonated drinks, and reduce salt intake to increase calcium absorption and reduce urinary calcium excretion, thereby increasing bone density. Regular bone density checks can help you understand your own bone condition in a timely manner and take appropriate preventive or treatment measures to help maintain bone health.

[0003] Increasing bone density can prevent pathological fractures caused by osteoporosis. For patients with osteoporosis, pathological fractures are very common. For example, a slight sneeze can cause broken ribs, and falling to the ground is likely to cause spinal collapse. If bone density is increased, it can also effectively reduce and prevent a series of potential symptoms caused by osteoporosis, such as systemic bone pain caused by osteoporosis in the elderly, and prevent the aggravation or occurrence of degenerative changes in the joints.

[0004] At present, the existing preparation technology of bone density-enhancing compositions has the following problems: first, the efficacy of existing bone density-enhancing compositions is not significant, and other drugs are needed to maintain bone density after stopping taking them; second, they are irritating, and long-term use will cause gastrointestinal discomfort and diarrhea; third, existing bone density-enhancing compositions will cause an acute increase in blood calcium levels in a short period of time, and long-term supplementation will cause vascular calcification, resulting in reduced vascular elasticity and thus increased blood pressure. Summary of the invention

[0005] In view of the above situation, in order to overcome the defects of the prior art, the present invention provides a collagen peptide composition for improving bone density and a preparation method thereof. In order to solve the problems that the existing bone density-improving composition is not effective, cannot maintain bone density after discontinuation, is irritating to the gastrointestinal tract, and damages the blood vessel wall after taking, the present invention uses bone nutrient nanoparticles, osteocyte metabolism-promoting microcapsules and a stabilizing, anti-inflammatory and antibacterial matrix to mix. The prepared collagen peptide composition for improving bone density has a high efficiency and lasting effect, is non-irritating, does not cause an acute increase in blood calcium levels, and does not cause an increase in blood pressure.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows: the present invention proposes a collagen peptide composition for improving bone density, and the raw materials for preparing the collagen peptide composition for improving bone density specifically include the following components in parts by weight:

[0007] 45-60 parts of bone nutrition nanoparticles, 35-55 parts of microcapsules promoting bone cell metabolism, 6-9 parts of glutathione, 12-18 parts of dodecyl maltoside, and 48-66 parts of trimethyl chitosan.

[0008] Preferably, the raw materials for preparing the bone nutrition nanoparticles include the following components in parts by weight: 20-30 parts of Ascophyllum nodosum, 15-25 parts of Gelidium agar, 18-26 parts of chimaera, 25-30 parts of beef tendon, 140-180 parts of papain, 32-38 parts of calcium chloride, and 40-45 parts of sodium carbonate; the raw materials for preparing the osteoblast metabolism microcapsules include the following components in parts by weight: 10-16 parts of Polygonum cuspidatum root, 13-18 parts of dandelion, 17-21 parts of Purslane, 18-24 parts of mackerel liver, 13-21 parts of peanuts, and 7-11 parts of sucrose fatty acid esters.

[0009] Preferably, the method for preparing the bone-nourishing nanoparticles comprises the following steps:

[0010] S1. Put the Ascophyllum nodosum, Gelidium agarifolia and ultrapure water into a stirrer with a power of 1.2-1.6 kW, the stirring temperature is 25-30°C, the stirring time is 10-15 min, the stirring speed is 120-140 r / min, and after mixing, soak for 3-4 h, put into an ultrasonic crusher with a power of 1.8-2.5 kW, the ultrasonic crushing frequency is 20 kHz, the ultrasonic crushing time is 20-30 min, and the ultrasonic crushing temperature is 0°C, and ultrasonic crushing is performed to obtain a seaweed mixture;

[0011] S2, placing the seaweed mixture prepared in S1 into a high-speed centrifuge with a power of 2.2-2.6 kW, the centrifugal temperature is 2°C, the centrifugal speed is 12000-15000 r / min, the centrifugal time is 13-18 min, and the precipitate is discarded by centrifugation to obtain a mixed seaweed solution;

[0012] S3, putting the silver shark, beef tendon and ultrapure water into a boiling pot with a power of 2.3-2.8 kW, the boiling temperature is 100°C, the boiling time is 2-3 h, and after boiling, putting them into a pulping machine with a power of 1.5-1.8 kW, the pulping speed is 1600-1900 r / min, the pulping time is 25-35 min, and the pulping temperature is 23-30°C. After pulping, put them into an enzymolysis tank with a power of 1.5-1.8 kW with papain, the enzymolysis temperature is 50-60°C, the enzymolysis speed is 110-130 r / min, and the enzymolysis time is 4-6h, and enzymolysis is performed to obtain a collagen peptide solution;

[0013] S4, putting the mixed seaweed solution prepared by S2 and the collagen peptide solution prepared by S3, calcium chloride and sodium carbonate into a stirrer with a power of 1.2-1.6 kW, adjusting the pH to 11 with a sodium hydroxide solution with a concentration of 3 mol / L, stirring at a temperature of 0°C, stirring for 6-10 min, stirring at a speed of 800-900 r / min, co-precipitating and putting into a high-speed centrifuge with a power of 2.2-2.6 kW, centrifuging at a temperature of 2°C, a speed of 12000-15000 r / min, centrifuging for 13-18 min, and discarding the supernatant to obtain a bone nutrition complex;

[0014] S5. Put the bone nutrition complex prepared in S4 into an ultrasonic pulverizer with a power of 2.8-3.2 kW, the ultrasonic pulverization frequency is 25 Hz, the ultrasonic pulverization temperature is 20-26° C., and the ultrasonic pulverization time is 20-30 min. After ultrasonic pulverization, bone nutrition nanoparticles are obtained.

[0015] Furthermore, in step S1, the weight ratio of the ultrapure water to Ascophyllum nodosum is 1.5-2:1, and the weight ratio of the ultrapure water to Gelidium agar is 1.3-1.8:1; in step S3, the weight ratio of the ultrapure water to silver mackerel is 1.3-1.6:1, and the weight ratio of the ultrapure water to beef shank is 1.5-1.8:1; in step S4, the concentration of the sodium hydroxide solution is 3 mol / L.

[0016] Preferably, the method for preparing the microcapsules for promoting osteocyte metabolism comprises the following steps:

[0017] L1. Put the root of Polygonum cuspidatum, dandelion and Purslane into a grinder with a power of 1.5-1.8 kW, the grinding temperature is 25-28°C, the grinding speed is 1200-1500 r / min, and the grinding time is 15-25 min. After grinding, filter with a sterile filter mesh with a pore size of 100 µm to obtain plant juice;

[0018] L2. Put the mackerel liver and peanuts into a pulping machine with a power of 1.5-1.8 kW, the pulping speed is 1600-1900 r / min, the pulping time is 25-35 min, the pulping temperature is 23-30° C., and the pulping is performed to obtain a wall material liquid;

[0019] L3, putting the plant juice prepared by L1, the wall material liquid prepared by L2, and the sucrose fatty acid ester into a vacuum homogenizer with a power of 2.9-3.3 kW, a vacuum degree of -0.05 MPa, a homogenization emulsification temperature of 30-50°C, a homogenization emulsification time of 30-40 min, and a homogenization emulsification speed of 1000-2000 r / min, and performing homogenization emulsification to obtain an emulsion promoting osteocyte metabolism;

[0020] L4. Place the osteocyte metabolism-promoting emulsion prepared in L3 into a vacuum freeze-nano spray dryer with a power of 2.3-2.8 kW, the vacuum degree is -0.05 MPa, the freeze-nano spray drying temperature is -40°C, the freeze-nano spray drying particle size is 100 nm, and the freeze-nano spray drying time is 2.5-3 h to obtain osteocyte metabolism-promoting microcapsules.

[0021] The present invention also proposes a method for preparing a collagen peptide composition for improving bone density, which specifically comprises the following steps:

[0022] Step 1, dissolving glutathione and dodecyl maltoside in ultrapure water, and putting them into a stirrer with a power of 1.2-1.6 kW with trimethyl chitosan, stirring at a temperature of 23-28° C., stirring for 13-18 min, stirring at a speed of 130-150 r / min, and stirring to obtain a stabilizing anti-inflammatory and antibacterial matrix;

[0023] Step 2: Place the bone nutrient nanoparticles and osteoblast metabolism-promoting microcapsules into a stirrer with a power of 1.2-1.6 kW, stir at a temperature of 23-28° C., stir for 12-16 min, stir at a speed of 110-130 r / min, and mix evenly to obtain a premix for improving bone density;

[0024] Step 3: Place the bone density enhancing premix prepared in step 2 into the stabilizing, anti-inflammatory and antibacterial matrix prepared in step 1, and use an ultrasonic stirrer with a power of 1.8 kW, an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min to uniformly disperse the premix to obtain a collagen peptide mixture that enhances bone density;

[0025] Step 4: Place the collagen peptide mixture for improving bone density prepared in step 3 into a Chinese and Western medicine tablet press with a power of 1.8-2.2 kW, the tableting temperature is 55-58°C, the tableting time is 15-20 min, the tableting diameter is 4-6 mm, and after tableting, place it in a dryer with a power of 1.4-1.8 kW, the drying temperature is 50-55°C, the drying time is 30-40 min, and after drying, a collagen peptide composition for improving bone density is obtained.

[0026] Preferably, in step 1, the mass fraction of glutathione in ultrapure water is 30-36%, and the mass fraction of dodecyl maltoside in ultrapure water is 32-43%.

[0027] The beneficial effects achieved by the present invention are as follows:

[0028] The present invention uses Ascophyllum nodosum and Gelidium agar to grind and ultrasonically crush to obtain a mixed seaweed solution rich in sodium alginate and seaweed calcium. After high-temperature boiling, the silver mackerel and beef tendon are mildly enzymatically hydrolyzed using papain to form a collagen peptide solution rich in type I and type III collagen. Type I collagen is the protein with the highest content in bones and has an important influence on the load-bearing capacity, tensile strength and torsional stiffness of bones after calcification. Type III collagen helps to regulate the fiber diameter of type I collagen. Collagen contains amino acid components such as glycine and hydroxyproline, which can combine with calcium ions in the body to form a soluble complex, thereby improving the bioavailability of calcium. It promotes calcium absorption to achieve the effect of calcium supplementation. Collagen peptides are used as synthetic raw materials to promote the formation of bone collagen and effectively improve bone density. Calcium chloride and sodium carbonate are co-precipitated to form amorphous calcium carbonate. Amorphous calcium carbonate has higher solubility and biocompatibility, higher specific surface area and porosity, and can efficiently adsorb collagen peptide solution. The carboxyl group of sodium alginate can undergo ion exchange reaction with calcium ions on the surface of amorphous calcium carbonate to form a cross-linked network structure. The addition of sodium alginate can reduce the degradation rate of amorphous calcium carbonate and improve its stability in an acidic environment, thereby achieving the regulation of the release rate of collagen peptides and calcium ions. It will not cause blood in the blood after taking it. Acute increase in calcium levels; after crushing and filtering the roots of Polygonum cuspidatum, dandelion, and purslane, a plant juice rich in vitamin A, vitamin C, and vitamin K is obtained, which helps the body absorb vitamin D and calcium, and cooperates with bone nutrition nanoparticles to promote the metabolic proliferation ability of osteoblasts, osteocytes, and chondrocytes, inhibit the occurrence of inflammatory reactions, and maintain the absorption and deposition of calcium in the bones for a long time, preventing calcium from being lost from the bones too quickly. Mackerel liver and peanuts are ground into pulp. Polygonum cuspidatum roots and peanuts are rich in resveratrol, which cooperates with acetyltaraxacum alcohol and kaempferol in the plant juice to directly act on osteoclasts, inhibit the activity of osteoclasts, and can also dilate blood vessels to maintain blood pressure stability. After the osteoblast metabolism emulsion is vacuum-frozen and nano-spray-dried, the prepared osteoblast metabolism microcapsules accelerate the absorption and utilization of the components in the bone nutrition nanoparticles by the bones; glutathione and dodecyl maltoside are dissolved in ultrapure water and mixed with trimethyl chitosan to form a stabilizing anti-inflammatory and antibacterial matrix, which can protect the stability of the effective components, inhibit the occurrence of inflammation in the intestine, and adhere to the surface of intestinal cells. The bone nutrition nanoparticles and osteoblast metabolism microcapsules are evenly dispersed in the stabilizing anti-inflammatory and antibacterial matrix. The prepared collagen peptide composition for improving bone density has a significant effect on improving bone density, maintains bone density for a long time, is non-irritating, and keeps the blood pressure stable in the body. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] In order to more clearly illustrate the present invention or the technical solutions in the prior art, the following will be described in a clear and understandable manner in conjunction with the accompanying drawings. Obviously, the drawings described below are only for the present invention, and for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0030] Figure 1 This is an electron microscopic image of the bone nutrition complex of the present invention;

[0031] Figure 2 This is a graph showing the femoral neck bone density results of rats described in Experimental Example 1 of the present invention;

[0032] Figure 3 This is the result diagram of the midpoint bone density of the femur of rats described in Experimental Example 1 of the present invention;

[0033] Figure 4 This is a graph showing the bone density results of the distal end of the femur of rats described in Experimental Example 1 of the present invention;

[0034] Figure 5 This is a graph showing the changes in systolic pressure in the rat tail artery described in Experimental Example 3 of the present invention. DETAILED DESCRIPTION

[0035] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments; based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0036] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein may be applied to the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only and are not intended to limit the content of this application.

[0037] The experimental methods in the following examples are conventional methods unless otherwise specified; the experimental materials and test strains used in the following examples are purchased from commercial channels unless otherwise specified.

[0038] Example 1: This example provides a collagen peptide composition for improving bone density and a preparation method thereof. The collagen peptide composition for improving bone density comprises the following components in parts by weight:

[0039] 45 parts of bone nutrition nanoparticles, 35 parts of osteocyte metabolism promoting microcapsules, 6 parts of glutathione, 12 parts of dodecyl maltoside, and 48 parts of trimethyl chitosan.

[0040] The raw materials for preparing the bone nutrition nanoparticles include the following components in parts by weight: 20 parts of Ascophyllum nodosum, 15 parts of Gelidium agar, 18 parts of Chimaera, 25 parts of Beef tendon, 140 parts of papain, 32 parts of calcium chloride, and 40 parts of sodium carbonate; the raw materials for preparing the osteoblast metabolism microcapsules include the following components in parts by weight: 10 parts of Polygonum cuspidatum root, 13 parts of dandelion, 17 parts of Purslane, 18 parts of mackerel liver, 13 parts of peanuts, and 7 parts of sucrose fatty acid ester.

[0041] The method for preparing the bone nutrition nanoparticles specifically comprises the following steps:

[0042] S1. Put the Ascophyllum nodosum, Gelidium amansoniae and ultrapure water into a stirrer with a power of 1.2 kW, a stirring temperature of 25°C, a stirring time of 10 min, a stirring speed of 120 r / min, mix well and soak for 3 h, put into an ultrasonic crusher with a power of 1.8 kW, an ultrasonic crushing frequency of 20 kHz, an ultrasonic crushing time of 20 min, and an ultrasonic crushing temperature of 0°C, and perform ultrasonic crushing to obtain a seaweed mixture;

[0043] S2, placing the seaweed mixture prepared in S1 into a high-speed centrifuge with a power of 2.2 kW, the centrifugal temperature is 2°C, the centrifugal speed is 12000 r / min, the centrifugal time is 13 min, and the precipitate is discarded by centrifugation to obtain a mixed seaweed solution;

[0044] S3, put the silver shark, beef tendon and ultrapure water into a boiling pot with a power of 2.3 kW, the boiling temperature is 100°C, the boiling time is 2 h, and after boiling, put them into a pulping machine with a power of 1.5 kW, the pulping speed is 1600 r / min, the pulping time is 25 min, and the pulping temperature is 23°C. After pulping, put them into an enzymolysis tank with a power of 1.5 kW with papain, the enzymolysis temperature is 50°C, the enzymolysis speed is 110 r / min, and the enzymolysis time is 4 h, and enzymolysis is performed to obtain a collagen peptide solution;

[0045] S4, putting the mixed seaweed solution prepared by S2 and the collagen peptide solution prepared by S3, calcium chloride and sodium carbonate into a 1.2 kW agitator, adjusting the pH to 11 with a 3 mol / L sodium hydroxide solution, stirring at 0°C, stirring for 6 min, stirring at 800 r / min, co-precipitating and putting into a 2.2 kW high-speed centrifuge, centrifuging at 2°C, at 12000 r / min, at 13 min, centrifuging and discarding the supernatant to obtain a bone nutrition complex;

[0046] S5. Put the bone nutrition complex prepared in S4 into an ultrasonic pulverizer with a power of 2.8 kW, the ultrasonic pulverization frequency is 25 Hz, the ultrasonic pulverization temperature is 20°C, and the ultrasonic pulverization time is 20 min. After ultrasonic pulverization, bone nutrition nanoparticles are obtained.

[0047] In step S1, the weight ratio of the ultrapure water to Ascophyllum nodosum is 1.5:1, and the weight ratio of the ultrapure water to Gelidium agar is 1.3:1; in step S3, the weight ratio of the ultrapure water to Chimaera bream is 1.3:1, and the weight ratio of the ultrapure water to Beef tendon is 1.5:1; in step S4, the concentration of the sodium hydroxide solution is 3 mol / L.

[0048] The preparation method of the microcapsules for promoting osteocyte metabolism specifically comprises the following steps:

[0049] L1. Put the root of Polygonum cuspidatum, dandelion and Purslane into a grinder with a power of 1.5 kW, the grinding temperature is 25°C, the grinding speed is 1200 r / min, and the grinding time is 15 min. After grinding, use a sterile filter mesh with a pore size of 100 µm to filter to obtain plant juice;

[0050] L2, putting mackerel liver and peanuts into a pulping machine with a power of 1.5 kW, with a refining speed of 1600 r / min, a refining time of 25 min, and a refining temperature of 23°C, to obtain a wall material liquid;

[0051] L3, placing the plant juice prepared by L1, the wall material liquid prepared by L2, and the sucrose fatty acid ester into a vacuum homogenizer with a power of 2.9 kW, with a vacuum degree of -0.05 MPa, a homogenization emulsification temperature of 30°C, a homogenization emulsification time of 30 min, and a homogenization emulsification speed of 1000 r / min, and performing homogenization emulsification to obtain an emulsion that promotes osteocyte metabolism;

[0052] L4. Place the osteocyte metabolism-promoting emulsion prepared in L3 into a vacuum freeze-nano spray dryer with a power of 2.3 kW, the vacuum degree is -0.05 MPa, the freeze-nano spray drying temperature is -40°C, the freeze-nano spray drying particle size is 100 nm, and the freeze-nano spray drying time is 2.5 h to obtain osteocyte metabolism-promoting microcapsules.

[0053] This embodiment also provides a method for preparing a collagen peptide composition for improving bone density, which specifically comprises the following steps:

[0054] Step 1, dissolving glutathione and dodecyl maltoside in ultrapure water, and putting them into a stirrer with a power of 1.2 kW with trimethyl chitosan, stirring at a temperature of 23°C, stirring for 13 min, stirring at a speed of 130 r / min, and stirring to obtain a stabilizing anti-inflammatory and antibacterial matrix;

[0055] Step 2: Place the bone nutrient nanoparticles and osteoblast metabolism-promoting microcapsules into a 1.2 kW stirrer at a stirring temperature of 23° C. for 12 min at a stirring speed of 110 r / min, and mix them evenly to obtain a premix for improving bone density;

[0056] Step 3: Place the bone density enhancing premix prepared in step 2 into the stabilizing, anti-inflammatory and antibacterial matrix prepared in step 1, and use an ultrasonic stirrer with a power of 1.8 kW, an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min to uniformly disperse the premix to obtain a collagen peptide mixture that enhances bone density;

[0057] Step 4: Place the collagen peptide mixture for improving bone density prepared in step 3 into a Chinese and Western medicine tablet press with a power of 1.8 kW, the tableting temperature is 55°C, the tableting time is 15 min, the tableting diameter is 4 mm, and after tableting, place it in a dryer with a power of 1.4 kW, the drying temperature is 50°C, the drying time is 30 min, and after drying, a collagen peptide composition for improving bone density is obtained.

[0058] In step 1, the mass fraction of glutathione in ultrapure water is 30%, and the mass fraction of dodecyl maltoside in ultrapure water is 32%.

[0059] Example 2: This example provides a collagen peptide composition for improving bone density and a preparation method thereof. The collagen peptide composition for improving bone density comprises the following components in parts by weight:

[0060] 55 parts of bone nutrition nanoparticles, 40 parts of osteocyte metabolism promoting microcapsules, 7 parts of glutathione, 15 parts of dodecyl maltoside, and 53 parts of trimethyl chitosan.

[0061] The raw materials for preparing the bone nutrition nanoparticles include the following components in parts by weight: 25 parts of Ascophyllum nodosum, 20 parts of Gelidium agar, 22 parts of Chimaera, 28 parts of beef tendon, 160 parts of papain, 35 parts of calcium chloride, and 43 parts of sodium carbonate; the raw materials for preparing the osteoblast metabolism microcapsules include the following components in parts by weight: 13 parts of Polygonum cuspidatum root, 16 parts of dandelion, 19 parts of Purslane, 21 parts of mackerel liver, 17 parts of peanuts, and 9 parts of sucrose fatty acid ester.

[0062] The method for preparing the bone nutrition nanoparticles specifically comprises the following steps:

[0063] S1. Put the Ascophyllum nodosum, Gelidium agarifolia and ultrapure water into a stirrer with a power of 1.4 kW, a stirring temperature of 28°C, a stirring time of 13 min, a stirring speed of 130 r / min, mix well, soak for 3.5 h, put into an ultrasonic crusher with a power of 2.2 kW, an ultrasonic crushing frequency of 20 kHz, an ultrasonic crushing time of 25 min, and an ultrasonic crushing temperature of 0°C, and perform ultrasonic crushing to obtain a seaweed mixture;

[0064] S2, placing the seaweed mixture prepared in S1 into a high-speed centrifuge with a power of 2.4 kW, the centrifugal temperature is 2°C, the centrifugal speed is 13000 r / min, the centrifugal time is 16 min, and the precipitate is discarded by centrifugation to obtain a mixed seaweed solution;

[0065] S3, putting the silver shark, beef tendon and ultrapure water into a boiling pot with a power of 2.6 kW, the boiling temperature is 100°C, the boiling time is 2.5 h, and after boiling, putting them into a pulping machine with a power of 1.7 kW, the pulping speed is 1800 r / min, the pulping time is 30 min, and the pulping temperature is 27°C, and after pulping, putting them into an enzymolysis tank with a power of 1.6 kW with papain, the enzymolysis temperature is 55°C, the enzymolysis speed is 120 r / min, the enzymolysis time is 5 h, and enzymolysis is performed to obtain a collagen peptide solution;

[0066] S4, putting the mixed seaweed solution prepared by S2 and the collagen peptide solution prepared by S3, calcium chloride and sodium carbonate into a 1.4 kW agitator, adjusting the pH to 11 with a 3 mol / L sodium hydroxide solution, stirring at 0°C, stirring for 8 min, stirring at 800 r / min, co-precipitating and putting into a 2.4 kW high-speed centrifuge, centrifuging at 2°C, at 13000 r / min, at 16 min, centrifuging and discarding the supernatant to obtain a bone nutrition complex;

[0067] S5. Put the bone nutrition complex prepared in S4 into an ultrasonic pulverizer with a power of 3 kW, the ultrasonic pulverization frequency is 25 Hz, the ultrasonic pulverization temperature is 23° C., and the ultrasonic pulverization time is 25 min. After ultrasonic pulverization, bone nutrition nanoparticles are obtained.

[0068] In step S1, the weight ratio of the ultrapure water to Ascophyllum nodosum is 1.8:1, and the weight ratio of the ultrapure water to Gelidium agar is 1.6:1; in step S3, the weight ratio of the ultrapure water to Chimaera bream is 1.4:1, and the weight ratio of the ultrapure water to Beef tendon is 1.7:1; in step S4, the concentration of the sodium hydroxide solution is 3 mol / L.

[0069] The preparation method of the microcapsules for promoting osteocyte metabolism specifically comprises the following steps:

[0070] L1. Put the root of Polygonum cuspidatum, dandelion and Purslane into a grinder with a power of 1.6 kW, the grinding temperature is 27°C, the grinding speed is 1300 r / min, and the grinding time is 20 min. After grinding, use a sterile filter mesh with a pore size of 100 µm to filter to obtain plant juice;

[0071] L2, putting mackerel liver and peanuts into a pulping machine with a power of 1.6 kW, with a refining speed of 1700 r / min, a refining time of 30 min, and a refining temperature of 26°C, to obtain a wall material liquid;

[0072] L3, putting the plant juice prepared by L1, the wall material liquid prepared by L2, and the sucrose fatty acid ester into a vacuum homogenizer with a power of 3.1 kW, with a vacuum degree of -0.05 MPa, a homogenization emulsification temperature of 40°C, a homogenization emulsification time of 35 min, and a homogenization emulsification speed of 1000 r / min, and performing homogenization emulsification to obtain an emulsion that promotes osteocyte metabolism;

[0073] L4. Place the osteocyte metabolism-promoting emulsion prepared in L3 into a vacuum freeze-nano spray dryer with a power of 2.6 kW, the vacuum degree is -0.05 MPa, the freeze-nano spray drying temperature is -40°C, the freeze-nano spray drying particle size is 100 nm, and the freeze-nano spray drying time is 2.8 h to obtain osteocyte metabolism-promoting microcapsules.

[0074] This embodiment also provides a method for preparing a collagen peptide composition for improving bone density, which specifically comprises the following steps:

[0075] Step 1, dissolving glutathione and dodecyl maltoside in ultrapure water, and putting them into a stirrer with a power of 1.4 kW with trimethyl chitosan, stirring at a temperature of 25°C, stirring for 16 min, stirring at a speed of 140 r / min, and stirring to obtain a stabilizing anti-inflammatory and antibacterial matrix;

[0076] Step 2: Place the bone nutrient nanoparticles and osteoblast metabolism-promoting microcapsules into a 1.4 kW stirrer at a stirring temperature of 26° C. for 14 min and a stirring speed of 120 r / min, and mix them evenly to obtain a premix for improving bone density;

[0077] Step 3: Place the bone density enhancing premix prepared in step 2 into the stabilizing, anti-inflammatory and antibacterial matrix prepared in step 1, and use an ultrasonic stirrer with a power of 1.8 kW, an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min to uniformly disperse the premix to obtain a collagen peptide mixture that enhances bone density;

[0078] Step 4: Place the collagen peptide mixture for improving bone density prepared in step 3 into a Chinese and Western medicine tablet press with a power of 2 kW, the tableting temperature is 56°C, the tableting time is 18 min, the tableting diameter is 5 mm, and after tableting, place it in a dryer with a power of 1.6 kW, the drying temperature is 53°C, the drying time is 35 min, and after drying, a collagen peptide composition for improving bone density is obtained.

[0079] In step 1, the mass fraction of glutathione in ultrapure water is 33%, and the mass fraction of dodecyl maltoside in ultrapure water is 38%.

[0080] Example 3: This example provides a collagen peptide composition for improving bone density and a preparation method thereof. The collagen peptide composition for improving bone density comprises the following components in parts by weight:

[0081] 60 parts of bone nutrition nanoparticles, 55 parts of osteocyte metabolism promoting microcapsules, 9 parts of glutathione, 18 parts of dodecyl maltoside, and 66 parts of trimethyl chitosan.

[0082] The raw materials for preparing the bone nutrition nanoparticles include the following components in parts by weight: 30 parts of Ascophyllum nodosum, 25 parts of Gelidium agar, 26 parts of Chimaera, 30 parts of Beef tendon, 180 parts of papain, 38 parts of calcium chloride, and 45 parts of sodium carbonate; the raw materials for preparing the osteoblast metabolism microcapsules include the following components in parts by weight: 16 parts of Polygonum cuspidatum root, 18 parts of dandelion, 21 parts of Purslane, 24 parts of mackerel liver, 21 parts of peanuts, and 11 parts of sucrose fatty acid ester.

[0083] The method for preparing the bone nutrition nanoparticles specifically comprises the following steps:

[0084] S1. Put the Ascophyllum nodosum, Gelidium amansoniae and ultrapure water into a stirrer with a power of 1.6 kW, a stirring temperature of 30°C, a stirring time of 15 min, a stirring speed of 140 r / min, mix well and soak for 4 h, put into an ultrasonic crusher with a power of 2.5 kW, an ultrasonic crushing frequency of 20 kHz, an ultrasonic crushing time of 30 min, and an ultrasonic crushing temperature of 0°C, and perform ultrasonic crushing to obtain a seaweed mixture;

[0085] S2, placing the seaweed mixture prepared in S1 into a high-speed centrifuge with a power of 2.6 kW, the centrifugal temperature is 2°C, the centrifugal speed is 15000 r / min, the centrifugal time is 18 min, and the precipitate is discarded by centrifugation to obtain a mixed seaweed solution;

[0086] S3, putting the silver shark, beef tendon and ultrapure water into a boiling pot with a power of 2.8 kW, the boiling temperature is 100°C, the boiling time is 3 h, and after boiling, putting them into a pulping machine with a power of 1.8 kW, the pulping speed is 1900 r / min, the pulping time is 35 min, and the pulping temperature is 30°C. After pulping, put them into an enzymolysis tank with a power of 1.8 kW with papain, the enzymolysis temperature is 60°C, the enzymolysis speed is 130 r / min, and the enzymolysis time is 6 h, and enzymolysis is performed to obtain a collagen peptide solution;

[0087] S4, putting the mixed seaweed solution prepared by S2, the collagen peptide solution prepared by S3, calcium chloride and sodium carbonate into a 1.6 kW agitator, adjusting the pH to 11 with a 3 mol / L sodium hydroxide solution, stirring at 0°C, stirring for 10 min, stirring at 900 r / min, co-precipitating, putting into a 2.6 kW high-speed centrifuge, centrifuging at 2°C, centrifuging at 15000 r / min, centrifuging for 18 min, centrifuging and discarding the supernatant to obtain a bone nutrition complex;

[0088] S5. Put the bone nutrition complex prepared in S4 into an ultrasonic pulverizer with a power of 3.2 kW, the ultrasonic pulverization frequency is 25 Hz, the ultrasonic pulverization temperature is 26° C., and the ultrasonic pulverization time is 30 min. After ultrasonic pulverization, bone nutrition nanoparticles are obtained.

[0089] In step S1, the weight ratio of the ultrapure water to Ascophyllum nodosum is 2:1, and the weight ratio of the ultrapure water to Gelidium agar is 1.8:1; in step S3, the weight ratio of the ultrapure water to Chimaera serrata is 1.6:1, and the weight ratio of the ultrapure water to Beef tendon is 1.8:1; in step S4, the concentration of the sodium hydroxide solution is 3 mol / L.

[0090] The preparation method of the microcapsules for promoting osteocyte metabolism specifically comprises the following steps:

[0091] L1. Put the root of Polygonum cuspidatum, dandelion and purslane into a grinder with a power of 1.8 kW, the grinding temperature is 28°C, the grinding speed is 1500 r / min, and the grinding time is 25 min. After grinding, use a sterile filter mesh with a pore size of 100 µm to filter to obtain plant juice;

[0092] L2, putting mackerel liver and peanuts into a pulping machine with a power of 1.8 kW, with a refining speed of 1900 r / min, a refining time of 35 min, and a refining temperature of 30°C, to obtain a wall material liquid;

[0093] L3, putting the plant juice prepared by L1, the wall material liquid prepared by L2, and the sucrose fatty acid ester into a vacuum homogenizer with a power of 3.3 kW, with a vacuum degree of -0.05 MPa, a homogenization emulsification temperature of 50°C, a homogenization emulsification time of 40 min, and a homogenization emulsification speed of 2000 r / min, and performing homogenization emulsification to obtain an emulsion promoting osteocyte metabolism;

[0094] L4. Place the osteocyte metabolism-promoting emulsion prepared in L3 into a vacuum freeze-nano spray dryer with a power of 2.8 kW, the vacuum degree is -0.05 MPa, the freeze-nano spray drying temperature is -40°C, the freeze-nano spray drying particle size is 100 nm, and the freeze-nano spray drying time is 3 h to obtain osteocyte metabolism-promoting microcapsules.

[0095] This embodiment also provides a method for preparing a collagen peptide composition for improving bone density, which specifically comprises the following steps:

[0096] Step 1, dissolving glutathione and dodecyl maltoside in ultrapure water, and putting them into a stirrer with a power of 1.6 kW with trimethyl chitosan, stirring at a temperature of 28°C, stirring for 18 min, stirring at a speed of 150 r / min, and stirring to obtain a stabilizing anti-inflammatory and antibacterial matrix;

[0097] Step 2: Place the bone nutrient nanoparticles and osteoblast metabolism-promoting microcapsules into a 1.6 kW stirrer at a stirring temperature of 28° C. for 16 min and a stirring speed of 130 r / min, and mix them evenly to obtain a premix for improving bone density;

[0098] Step 3: Place the bone density enhancing premix prepared in step 2 into the stabilizing, anti-inflammatory and antibacterial matrix prepared in step 1, and use an ultrasonic stirrer with a power of 1.8 kW, an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min to uniformly disperse the premix to obtain a collagen peptide mixture that enhances bone density;

[0099] Step 4: Place the collagen peptide mixture for improving bone density prepared in step 3 into a 2.2 kW Chinese and Western medicine tablet press, the tableting temperature is 58°C, the tableting time is 20 min, the tableting diameter is 6 mm, and after tableting, place it in a dryer with a power of 1.8 kW, the drying temperature is 55°C, the drying time is 40 min, and after drying, a collagen peptide composition for improving bone density is obtained.

[0100] In step 1, the mass fraction of glutathione in ultrapure water is 36%, and the mass fraction of dodecyl maltoside in ultrapure water is 43%.

[0101] Example 4: This example provides a collagen peptide composition for improving bone density and a preparation method thereof. The collagen peptide composition for improving bone density comprises the following components in parts by weight:

[0102] 50 parts of bone nutrition nanoparticles, 38 parts of osteocyte metabolism promoting microcapsules, 8 parts of glutathione, 13 parts of dodecyl maltoside, and 52 parts of trimethyl chitosan.

[0103] The raw materials for preparing the bone nutrition nanoparticles include the following components in parts by weight: 23 parts of Ascophyllum nodosum, 18 parts of Gelidium agar, 20 parts of Chimaera, 26 parts of Beef tendon, 150 parts of papain, 33 parts of calcium chloride, and 42 parts of sodium carbonate; the raw materials for preparing the osteoblast metabolism microcapsules include the following components in parts by weight: 12 parts of Polygonum cuspidatum root, 15 parts of dandelion, 18 parts of Purslane, 20 parts of mackerel liver, 15 parts of peanuts, and 8 parts of sucrose fatty acid ester.

[0104] The method for preparing the bone nutrition nanoparticles specifically comprises the following steps:

[0105] S1. Put the Ascophyllum nodosum, Gelidium agarifolia and ultrapure water into a stirrer with a power of 1.3 kW, a stirring temperature of 26°C, a stirring time of 12 min, a stirring speed of 120 r / min, mix well, soak for 3.3 h, put into an ultrasonic crusher with a power of 1.9 kW, an ultrasonic crushing frequency of 20 kHz, an ultrasonic crushing time of 23 min, and an ultrasonic crushing temperature of 0°C, and perform ultrasonic crushing to obtain a seaweed mixture;

[0106] S2, placing the seaweed mixture prepared in S1 into a high-speed centrifuge with a power of 2.3 kW, the centrifugal temperature is 2°C, the centrifugal speed is 12000 r / min, the centrifugal time is 15 min, and the precipitate is discarded by centrifugation to obtain a mixed seaweed solution;

[0107] S3, putting the silver mackerel, beef tendon and ultrapure water into a 2.5 kW boiling pot, the boiling temperature is 100°C, the boiling time is 2.3 h, after boiling, putting into a 1.6 kW refiner, the refining speed is 1700 r / min, the refining time is 28 min, the refining temperature is 26°C, after refining, putting into an enzymolysis tank with a power of 1.5 kW with papain, the enzymolysis temperature is 52°C, the enzymolysis speed is 110 r / min, the enzymolysis time is 4.5 h, and enzymolysis is performed to obtain a collagen peptide solution;

[0108] S4, putting the mixed seaweed solution prepared by S2, the collagen peptide solution prepared by S3, calcium chloride and sodium carbonate into a 1.3 kW agitator, adjusting the pH to 11 with a 3 mol / L sodium hydroxide solution, stirring at 0°C, stirring for 7 min, stirring at 800 r / min, co-precipitating, putting into a 2.3 kW high-speed centrifuge, centrifuging at 2°C, centrifuging at 12000 r / min, centrifuging for 15 min, and discarding the supernatant to obtain a bone nutrition complex;

[0109] S5. Put the bone nutrition complex prepared in S4 into an ultrasonic pulverizer with a power of 2.9 kW, the ultrasonic pulverization frequency is 25 Hz, the ultrasonic pulverization temperature is 21° C., and the ultrasonic pulverization time is 23 min. After ultrasonic pulverization, bone nutrition nanoparticles are obtained.

[0110] In step S1, the weight ratio of the ultrapure water to Ascophyllum nodosum is 1.6:1, and the weight ratio of the ultrapure water to Gelidium agar is 1.5:1; in step S3, the weight ratio of the ultrapure water to Chimaera bream is 1.3:1, and the weight ratio of the ultrapure water to Beef tendon is 1.6:1; in step S4, the concentration of the sodium hydroxide solution is 3 mol / L.

[0111] The preparation method of the microcapsules for promoting osteocyte metabolism specifically comprises the following steps:

[0112] L1. Put the root of Polygonum cuspidatum, dandelion and Purslane into a grinder with a power of 1.5 kW, the grinding temperature is 26°C, the grinding speed is 1200 r / min, and the grinding time is 18 min. After grinding, use a sterile filter mesh with a pore size of 100 µm to filter to obtain plant juice;

[0113] L2, putting mackerel liver and peanuts into a pulping machine with a power of 1.5 kW, with a refining speed of 1600 r / min, a refining time of 28 min, and a refining temperature of 25°C, to obtain a wall material liquid;

[0114] L3, putting the plant juice prepared by L1, the wall material liquid prepared by L2, and the sucrose fatty acid ester into a vacuum homogenizer with a power of 3 kW, the vacuum degree is -0.05 MPa, the homogenization emulsification temperature is 35°C, the homogenization emulsification time is 33 min, the homogenization emulsification speed is 1000 r / min, and homogenization emulsification is performed to obtain an emulsion that promotes osteocyte metabolism;

[0115] L4. Place the osteocyte metabolism-promoting emulsion prepared in L3 into a vacuum freeze-nano spray dryer with a power of 2.5 kW, the vacuum degree is -0.05 MPa, the freeze-nano spray drying temperature is -40°C, the freeze-nano spray drying particle size is 100 nm, and the freeze-nano spray drying time is 2.6 h to obtain osteocyte metabolism-promoting microcapsules.

[0116] This embodiment also provides a method for preparing a collagen peptide composition for improving bone density, which specifically comprises the following steps:

[0117] Step 1, dissolving glutathione and dodecyl maltoside in ultrapure water, and putting them into a stirrer with a power of 1.3 kW with trimethyl chitosan, stirring at a temperature of 24°C, stirring for 15 min, stirring at a speed of 130 r / min, and stirring to obtain a stabilizing anti-inflammatory and antibacterial matrix;

[0118] Step 2: Place the bone nutrient nanoparticles and osteoblast metabolism-promoting microcapsules into a 1.3 kW stirrer at a stirring temperature of 25° C. for 13 min and a stirring speed of 110 r / min, and mix them evenly to obtain a premix for improving bone density;

[0119] Step 3: Place the bone density enhancing premix prepared in step 2 into the stabilizing, anti-inflammatory and antibacterial matrix prepared in step 1, and use an ultrasonic stirrer with a power of 1.8 kW, an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min to uniformly disperse the premix to obtain a collagen peptide mixture that enhances bone density;

[0120] Step 4: Place the collagen peptide mixture for improving bone density prepared in step 3 into a Chinese and Western medicine tablet press with a power of 1.9 kW, the tableting temperature is 55°C, the tableting time is 16 min, the tableting diameter is 5 mm, and after tableting, place it in a dryer with a power of 1.5 kW, the drying temperature is 52°C, the drying time is 33 min, and after drying, a collagen peptide composition for improving bone density is obtained.

[0121] In step 1, the mass fraction of glutathione in ultrapure water is 32%, and the mass fraction of dodecyl maltoside in ultrapure water is 35%.

[0122] Example 5: This example provides a collagen peptide composition for improving bone density and a preparation method thereof. The collagen peptide composition for improving bone density comprises the following components in parts by weight:

[0123] 58 parts of bone nutrition nanoparticles, 52 parts of osteocyte metabolism promoting microcapsules, 8 parts of glutathione, 17 parts of dodecyl maltoside, and 60 parts of trimethyl chitosan.

[0124] The raw materials for preparing the bone nutrition nanoparticles include the following components in parts by weight: 28 parts of Ascophyllum nodosum, 23 parts of Gelidium agar, 25 parts of Chimaera, 29 parts of Beef tendon, 170 parts of papain, 37 parts of calcium chloride, and 44 parts of sodium carbonate; the raw materials for preparing the osteoblast metabolism microcapsules include the following components in parts by weight: 15 parts of Polygonum cuspidatum root, 17 parts of dandelion, 20 parts of Purslane, 22 parts of mackerel liver, 19 parts of peanuts, and 10 parts of sucrose fatty acid ester.

[0125] The method for preparing the bone nutrition nanoparticles specifically comprises the following steps:

[0126] S1. Put the Ascophyllum nodosum, Gelidium agarifolia and ultrapure water into a stirrer with a power of 1.5 kW, a stirring temperature of 29°C, a stirring time of 14 min, a stirring speed of 140 r / min, mix well, soak for 3.8 h, put into an ultrasonic crusher with a power of 2.4 kW, an ultrasonic crushing frequency of 20 kHz, an ultrasonic crushing time of 28 min, and an ultrasonic crushing temperature of 0°C, and perform ultrasonic crushing to obtain a seaweed mixture;

[0127] S2, placing the seaweed mixture prepared in S1 into a high-speed centrifuge with a power of 2.5 kW, the centrifugal temperature is 2°C, the centrifugal speed is 14000 r / min, the centrifugal time is 17 min, and the precipitate is discarded by centrifugation to obtain a mixed seaweed solution;

[0128] S3, putting the silver shark, beef tendon and ultrapure water into a boiling pot with a power of 2.7 kW, the boiling temperature is 100°C, the boiling time is 2.8 h, and after boiling, putting them into a pulping machine with a power of 1.8 kW, the pulping speed is 1900 r / min, the pulping time is 32 min, and the pulping temperature is 29°C. After pulping, put them into an enzymolysis tank with a power of 1.7 kW with papain, the enzymolysis temperature is 58°C, the enzymolysis speed is 130 r / min, and the enzymolysis time is 5.5 h, and enzymolysis is performed to obtain a collagen peptide solution;

[0129] S4, putting the mixed seaweed solution prepared by S2, the collagen peptide solution prepared by S3, calcium chloride and sodium carbonate into a 1.5 kW agitator, adjusting the pH to 11 with a 3 mol / L sodium hydroxide solution, stirring at 0°C, stirring for 9 min, stirring at 900 r / min, co-precipitating, putting into a 2.5 kW high-speed centrifuge, centrifuging at 2°C, centrifuging at 14000 r / min, centrifuging for 17 min, centrifuging and discarding the supernatant to obtain a bone nutrition complex;

[0130] S5. Put the bone nutrition complex prepared in S4 into an ultrasonic pulverizer with a power of 3.1 kW, the ultrasonic pulverization frequency is 25 Hz, the ultrasonic pulverization temperature is 25°C, and the ultrasonic pulverization time is 28 min. After ultrasonic pulverization, bone nutrition nanoparticles are obtained.

[0131] In step S1, the weight ratio of the ultrapure water to Ascophyllum nodosum is 1.9:1, and the weight ratio of the ultrapure water to Gelidium agar is 1.7:1; in step S3, the weight ratio of the ultrapure water to Chimaera bream is 1.5:1, and the weight ratio of the ultrapure water to Beef tendon is 1.8:1; in step S4, the concentration of the sodium hydroxide solution is 3 mol / L.

[0132] The preparation method of the microcapsules for promoting osteocyte metabolism specifically comprises the following steps:

[0133] L1. Put the root of Polygonum cuspidatum, dandelion and Purslane into a grinder with a power of 1.7 kW, the grinding temperature is 28°C, the grinding speed is 1400 r / min, and the grinding time is 23 min. After grinding, use a sterile filter mesh with a pore size of 100 µm to filter to obtain plant juice;

[0134] L2, putting mackerel liver and peanut into a pulping machine with a power of 1.7 kW, with a refining speed of 1800 r / min, a refining time of 32 min, and a refining temperature of 28°C, to obtain a wall material liquid;

[0135] L3, putting the plant juice prepared by L1, the wall material liquid prepared by L2, and the sucrose fatty acid ester into a vacuum homogenizer with a power of 3.2 kW, with a vacuum degree of -0.05 MPa, a homogenization emulsification temperature of 45°C, a homogenization emulsification time of 38 min, and a homogenization emulsification speed of 2000 r / min, and performing homogenization emulsification to obtain an emulsion that promotes osteocyte metabolism;

[0136] L4. Place the osteocyte metabolism-promoting emulsion prepared in L3 into a vacuum freeze-nano spray dryer with a power of 2.7 kW, the vacuum degree is -0.05 MPa, the freeze-nano spray drying temperature is -40°C, the freeze-nano spray drying particle size is 100 nm, and the freeze-nano spray drying time is 2.9 h to obtain osteocyte metabolism-promoting microcapsules.

[0137] This embodiment also provides a method for preparing a collagen peptide composition for improving bone density, which specifically comprises the following steps:

[0138] Step 1, dissolving glutathione and dodecyl maltoside in ultrapure water, and putting them into a stirrer with a power of 1.5 kW with trimethyl chitosan, stirring at a temperature of 26°C, stirring for 17 min, stirring at a speed of 150 r / min, and stirring to obtain a stabilizing anti-inflammatory and antibacterial matrix;

[0139] Step 2: Place the bone nutrient nanoparticles and osteoblast metabolism-promoting microcapsules into a 1.5 kW stirrer at a stirring temperature of 27° C. for 15 min and a stirring speed of 130 r / min, and mix them evenly to obtain a premix for improving bone density;

[0140] Step 3: Place the bone density enhancing premix prepared in step 2 into the stabilizing, anti-inflammatory and antibacterial matrix prepared in step 1, and use an ultrasonic stirrer with a power of 1.8 kW, an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min to uniformly disperse the premix to obtain a collagen peptide mixture that enhances bone density;

[0141] Step 4: Place the collagen peptide mixture for improving bone density prepared in step 3 into a 2.1 kW Chinese and Western medicine tablet press, the tableting temperature is 57°C, the tableting time is 19 min, the tableting diameter is 5 mm, and after tableting, place it in a dryer with a power of 1.7 kW, the drying temperature is 55°C, the drying time is 38 min, and after drying, a collagen peptide composition for improving bone density is obtained.

[0142] In step 1, the mass fraction of glutathione in ultrapure water is 35%, and the mass fraction of dodecyl maltoside in ultrapure water is 41%.

[0143] Comparative Example 1: This comparative example provides a composition for improving bone density and a preparation method thereof. The only difference from Example 1 is that the added components do not contain bone-nourishing nanoparticles, and the remaining components, component contents, and method steps are the same as those in Example 1.

[0144] Comparative Example 2: This comparative example provides a composition for improving bone density and a preparation method thereof. The only difference from Example 1 is that the added components do not include osteocyte metabolism-promoting microcapsules, and the remaining components, component contents, and method steps are the same as those in Example 1.

[0145] Experimental Example 1: Test to measure the effect of improving bone density.

[0146] The experimental steps for determining the bone density-enhancing effect of the collagen peptide composition prepared in Examples 1-5 of the present invention are as follows:

[0147] (1) 80 SD male rats, each weighing 220 g (purchased from Chengdu Dashuo Animal Co., Ltd.), were randomly divided into 8 groups of 10 rats each. The rats were housed in separate cages, which were kept clean and dry at a temperature of 24°C and a humidity of 50%. The rats were fed with free access to food and water and low-calcium feed (purchased from Xiaoshu Youtai Biotechnology Co., Ltd.);

[0148] (2) After feeding for 10 days, the rats were fasted for 24 hours and fed with 4.5 mg of the collagen peptide composition for improving bone density prepared in Examples 1-5, 4.5 mg of the composition for improving bone density prepared in Comparative Examples 1-2, and 4.5 mg of calcium carbonate, respectively, by gavage, once a day for 13 weeks.

[0149] (3) After 13 weeks, the rats were fasted for 24 h and killed by cervical dislocation. The left hip bones of the rats were separated and the skin and flesh were removed. The bone density of the left femoral neck, femoral midpoint and femoral distal end of the rats in each group was measured and recorded using the American DONE bone density analysis system and single-energy X-ray bone densitometer (SXA-2000);

[0150] (4) 80 SD male rats, each weighing 220 g (purchased from Chengdu Dashuo Animal Co., Ltd.), were randomly divided into 8 groups of 10 rats each. The rats were housed in separate cages, which were kept clean and dry at a temperature of 24°C and a humidity of 50%. The rats were fed with free access to food and water and low-calcium feed (purchased from Xiaoshu Youtai Biotechnology Co., Ltd.);

[0151] (5) After feeding for 10 days, the rats were fasted for 24 hours and fed by gavage. The rats in Example 1-5 groups were respectively fed with 4.5 mg of the collagen peptide composition for improving bone density prepared in Example 1-5, and the rats in Comparative Example 1-2 groups were respectively fed with 4.5 mg of the composition for improving bone density prepared in Comparative Example 1-2. The rats in the control group were fed with 4.5 mg of calcium carbonate. The feeding was continued once a day for 13 weeks and then stopped.

[0152] (6) After the 16th week, the rats were fasted for 24 hours and killed by cervical dislocation. The left hip bones of the rats were separated and the skin and flesh were removed. The bone density of the left femoral neck, femoral midpoint and femoral distal end of the rats in each group was measured and recorded using the American DONE bone density analysis system and single-energy X-ray bone densitometer (SXA-2000).

[0153] Result analysis:

[0154] Figure 1 This is an electron microscope image of the bone nutrition complex of the present invention. Figure 2 The results of the femoral neck bone density of rats described in Experimental Example 1 of the present invention are shown in the figure. As shown in the figure, the rats in Example 1-5 groups were fed 4.5 mg of the collagen peptide composition for improving bone density prepared in Example 1-5, respectively. After 13 weeks, the bone density of the left femoral neck of the rats in each group was 0.126 g / cm 2 , 0.128g / cm 2 , 0.133 g / cm 2 , 0.128 g / cm 2 , 0.131 g / cm 2 After stopping feeding for 3 weeks, the bone density of the left femoral neck of rats in each group was 0.132 g / cm 2 , 0.134 g / cm 2 , 0.138 g / cm 2 , 0.132 g / cm 2 , 0.136 g / cm 2 After the rats in groups 1 and 2 of comparative examples were fed with 4.5 mg of the bone density-enhancing composition prepared in comparative examples 1 and 2 for 13 weeks, the bone density of the left femoral neck of the rats in each group was 0.012 g / cm 2 , 0.116 g / cm 2 After stopping feeding for 3 weeks, the bone density of the left femoral neck of rats in each group was 0.008 g / cm 2 , 0.121 g / cm 2 After the rats in the control group were fed with 4.5 mg of calcium carbonate for 13 weeks, the bone density of the left femoral neck of the rats in the control group was 0.106 g / cm 2 After 3 weeks of feeding cessation, the bone density of the left femoral neck of the rats in the control group was 0.095 g / cm 2 ; Figure 3 The results of the midpoint bone density of the femur of rats described in Experimental Example 1 of the present invention are shown in the figure. As shown in the figure, the rats in the Example 1-5 groups were fed 4.5 mg of the collagen peptide composition for improving bone density prepared in Example 1-5, respectively. After 13 weeks, the midpoint bone density of the femur of the rats in each group was 0.138 g / cm 2, 0.14 g / cm 2 , 0.149 g / cm 2 , 0.138 g / cm 2 , 0.147g / cm 2 After stopping feeding for 3 weeks, the midpoint bone density of the femur of rats in each group was 0.141 g / cm 2 , 0.144 g / cm 2 , 0.153g / cm 2 , 0.143 g / cm 2 , 0.151 g / cm 2 After the rats in groups 1 and 2 of comparative examples were fed with 4.5 mg of the bone density-enhancing composition prepared in comparative examples 1 and 2 for 13 weeks, the midpoint bone density of the femur of the rats in each group was 0.098 g / cm 2 , 0.127 g / cm 2 After stopping feeding for 3 weeks, the midpoint bone density of the femur of rats in each group was 0.093 g / cm 2 , 0.131 g / cm 2 After the rats in the control group were fed with 4.5 mg of calcium carbonate for 13 weeks, the midpoint bone density of the femur of the rats in the control group was 0.119 g / cm 2 After 3 weeks of feeding cessation, the midpoint bone density of the femur of the control group rats was 0.116 g / cm 2 ; Figure 4 The results of the distal femoral bone density of rats described in Experimental Example 1 of the present invention are shown in the figure. As shown in the figure, the rats in Examples 1-5 were fed 4.5 mg of the collagen peptide composition for improving bone density prepared in Examples 1-5, respectively. After 13 weeks, the distal femoral bone density of the rats in each group was 0.128 g / cm 2 , 0.132 g / cm 2 , 0.138 g / cm 2 , 0.13 g / cm 2 , 0.135 g / cm 2 After stopping feeding for 3 weeks, the bone density of the distal end of the femur of rats in each group was 0.133 g / cm 2 , 0.136 g / cm 2 , 0.142 g / cm 2 , 0.134 g / cm 2 , 0.14 g / cm 2 After the rats in groups 1 and 2 of comparative examples were fed with 4.5 mg of the bone density-enhancing composition prepared in comparative examples 1 and 2 for 13 weeks, the bone density of the distal end of the femur of the rats in each group was 0.017 g / cm 2 、0.118 g / cm 2After stopping feeding for 3 weeks, the distal end bone density of the femur of rats in each group was 0.014 g / cm 2 , 0.12 g / cm 2 After the rats in the control group were fed with 4.5 mg of calcium carbonate for 13 weeks, the bone density of the distal end of the femur of the rats in the control group was 0.111 g / cm 2 After 3 weeks of feeding cessation, the bone density of the distal femur of the rats in the control group was 0.104 g / cm 2 This indicates that the bone nutrition nanoparticles prepared by the present invention have high stability in an acidic environment, release calcium for a long time, and promote osteocyte metabolism. The microcapsules accelerate the absorption and utilization of various components in the bone nutrition nanoparticles by bones, and have a significant and long-lasting effect in improving bone density.

[0155] Experimental Example 2: Gastrointestinal irritation measurement test.

[0156] The test steps for determining the gastrointestinal irritation of the collagen peptide composition for improving bone density prepared in Examples 1-5 of the present invention are as follows:

[0157] (1) 80 SD male rats, each weighing 220 g (purchased from Chengdu Dashuo Animal Co., Ltd.), were randomly divided into 8 groups of 10 rats. The rats were housed in separate cages, which were kept clean and dry at a temperature of 24°C and a humidity of 50%. The rats were fed with free access to food and water.

[0158] (2) After feeding for 10 days, the rats were fasted for 24 hours and fed by gavage. The rats in Example 1-5 groups were respectively fed with 4.5 mg of the collagen peptide composition for improving bone density prepared in Example 1-5, and the rats in Comparative Example 1-2 groups were respectively fed with 4.5 mg of the composition for improving bone density prepared in Comparative Example 1-2. The rats in the control group were fed with 4.5 mg of calcium carbonate. The feeding was continued once a day for 20 days and then stopped. The diarrhea rate of the rats on the 20th day was observed and recorded and the average value was taken. The diarrhea rate of the rats was calculated according to the formula: Diarrhea rate of rats (%) = number of rats with diarrhea in each group / total number of rats in each group × 100%.

[0159] Table 1. Rat irritation test table

[0160]

[0161] Result analysis:

[0162] Table 1 is a rat irritation measurement table. As shown in Table 1, the rats in Example 1-5 groups were fed 4.5 mg of the collagen peptide composition for improving bone density prepared in Example 1-5, and the rats in Comparative Example 1-2 groups were fed 4.5 mg of the composition for improving bone density prepared in Comparative Example 1-2, respectively. The feeding was stopped after 20 days. The diarrhea rate of the rats was 0% on the 20th day. The rats in the control group were fed 4.5 mg of calcium carbonate once a day. The feeding was stopped after 20 days. The diarrhea rate of the rats was 80% on the 20th day. This shows that the collagen peptide composition for improving bone density prepared by the present invention does not irritate the gastrointestinal tract and does not cause diarrhea when taken for a long time.

[0163] Experimental Example 3: Blood pressure impact measurement test.

[0164] The test steps for determining the effect of the collagen peptide composition for improving bone density prepared in Examples 1-5 of the present invention on blood pressure are as follows:

[0165] (1) 80 SD male rats, each weighing 220 g (purchased from Chengdu Dashuo Animal Co., Ltd.), were randomly divided into 8 groups of 10 rats. The rats were housed in separate cages, which were kept clean and dry at a temperature of 24°C and a humidity of 50%. The rats were fed with free access to food and water.

[0166] (2) After feeding for 10 days, the rats were fasted for 24 hours and fed with 4.5 mg of the collagen peptide composition for improving bone density prepared in Examples 1-5, 4.5 mg of the composition for improving bone density prepared in Comparative Examples 1-2, and 4.5 mg of calcium carbonate, respectively, by gavage, once a day for 13 weeks.

[0167] (3) Starting from the 6th week, the tail artery systolic blood pressure of the hypertensive rats in Example 1-5, Comparative Example 1-2, and the control group after intragastric administration in step (2) was measured using a fully automatic non-invasive blood pressure measurement system for mice and rats. The blood pressure was measured once a week until the end of feeding in the 13th week and the results were recorded.

[0168] Result analysis:

[0169] Figure 5The result of the change of the systolic blood pressure of the tail artery of the rats described in Experimental Example 3 of the present invention is shown in the figure. As shown in the figure, the rats in the Example 1-5 groups were fed 4.5 mg of the collagen peptide composition for improving bone density prepared in Examples 1-5 every day. From the 6th to the 13th week of feeding, the systolic blood pressure of the tail artery of the rats in the Example 3 group changed to 134.1 mmHg, 135.7 mmHg, 136.9 mmHg, 138.2 mmHg, 139.4 mmHg, 139.0 mmHg, 138.4 mmHg, and 138.2 mmHg. The rats in the comparative example 1-2 groups were fed 4.5 mg of the composition for improving bone density prepared in the comparative example 1-2 every day. From the 6th to the 13th week of feeding, the systolic blood pressure of the tail artery of the rats in the comparative example 1 group changed to 139.6 mmHg, 139.8 mmHg, 140.3 mmHg, 141.2 mmHg, 138.7 mmHg, 140 The systolic blood pressure of the tail artery of the rats in the control group was 156.4 mmHg, 159.3 mmHg, 160.6 mmHg, 162.4 mmHg, 163.3 mmHg, 165.7 mmHg, 166.4 mmHg, 168.7 mmHg, 171.3 mmHg, 172.7 mmHg, 173.6 mmHg, 174.7 mmHg, 175.9 mmHg, 176.9 mmHg, 177.8 mmHg, 178.9 mmHg, 179.1 mmHg, 180.3 mmHg, 181.7 mmHg, 182.4 mmHg, 183.3 mmHg, 184.7 mmHg, 185.9 mmHg, 186.9 mmHg, 187.9 mmHg, 188.9 mmHg, mmHg, indicating that the bone nutrition nanoparticles prepared by the present invention will not cause an acute increase in the blood calcium level after taking, and the osteoblast metabolism-promoting microcapsules can not only promote the absorption and utilization of the bone nutrition nanoparticles by the bones, but also dilate blood vessels and maintain the stability of the body's blood pressure.

[0170] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

[0171] The present invention and its implementation methods are described above, which is not restrictive. The drawings are only one of the implementation methods of the present invention, and the actual application is not limited thereto. In short, if ordinary technicians in the field are inspired by it and design methods and embodiments similar to the technical solution without creativity without departing from the purpose of the invention, they should all fall within the protection scope of the present invention.

Claims

1. A collagen peptide composition for improving bone density, characterized in that: The raw materials for preparing the collagen peptide composition for improving bone density include the following components in parts by weight: 45-60 parts of bone nutrition nanoparticles, 35-55 parts of microcapsules promoting osteocyte metabolism, 6-9 parts of glutathione, 12-18 parts of dodecyl maltoside, and 48-66 parts of trimethyl chitosan; The raw materials for preparing the bone nutrition nanoparticles include the following components in parts by weight: 20-30 parts of Ascophyllum nodosum, 15-25 parts of Gelidium agar, 18-26 parts of Chimaera, 25-30 parts of Beef tendon, 140-180 parts of papain, 32-38 parts of calcium chloride, and 40-45 parts of sodium carbonate; The raw materials for preparing the osteoblast metabolism-promoting microcapsules include the following components in parts by weight: 10-16 parts of Polygonum cuspidatum root, 13-18 parts of dandelion, 17-21 parts of Purslane, 18-24 parts of mackerel liver, 13-21 parts of peanuts, and 7-11 parts of sucrose fatty acid ester; The method for preparing the bone nutrition nanoparticles specifically comprises the following steps: S1, mixing Ascophyllum nodosum and Gelidium agar with ultrapure water, soaking for 3-4 hours, and performing ultrasonic crushing to obtain a seaweed mixture; S2, subjecting the seaweed mixture prepared in S1 to high-speed centrifugation, discarding the precipitate, and obtaining a mixed seaweed solution; S3, boiling and grinding the chimaera, beef tendon and ultrapure water, and then enzymolyzing with papain to obtain a collagen peptide solution; S4, mixing the mixed seaweed solution prepared in S2 with the collagen peptide solution, calcium chloride and sodium carbonate prepared in S3, adjusting the pH to 11 with sodium hydroxide solution, stirring to cause precipitation reaction, centrifuging and discarding the supernatant to obtain a bone nutrition complex; S5, subjecting the bone nutrition complex prepared in S4 to ultrasonic grinding to obtain bone nutrition nanoparticles; The preparation method of the microcapsules for promoting osteocyte metabolism specifically comprises the following steps: L1. Mix and crush the root of Polygonum cuspidatum, dandelion and purslane, and filter them through a sterile filter mesh with a pore size of 100 µm to obtain plant juice; L2, stirring and grinding mackerel liver and peanuts to obtain a wall material liquid; L3, homogenizing and emulsifying the plant juice prepared in L1, the wall material liquid prepared in L2, and sucrose fatty acid ester to obtain an emulsion promoting osteocyte metabolism; L4, the osteocyte metabolism promoting emulsion prepared in L3 is subjected to vacuum freeze nano spray drying to obtain osteocyte metabolism promoting microcapsules; The method for preparing the collagen peptide composition for improving bone density specifically comprises the following steps: Step 1, dissolving glutathione and dodecyl maltoside in ultrapure water, and then stirring and mixing with trimethyl chitosan to obtain a stabilizing anti-inflammatory and antibacterial matrix; Step 2: Evenly mix the bone nutrition nanoparticles and the osteoblast metabolism promoting microcapsules to obtain a premix for improving bone density; Step 3: placing the bone density enhancing premix prepared in step 2 into the stabilizing, anti-inflammatory and antibacterial matrix prepared in step 1, and uniformly dispersing the mixture by ultrasonication to obtain a collagen peptide mixture for enhancing bone density; Step 4: Tablet the collagen peptide mixture for improving bone density prepared in step 3, and dry it to obtain a collagen peptide composition for improving bone density.

2. The collagen peptide composition for improving bone density according to claim 1, characterized in that: In step S1, the weight ratio of the ultrapure water to the Ascophyllum nodosum is 1.5-2:1, and the weight ratio of the ultrapure water to the Gelidium agar is 1.3-1.8:

1.

3. The collagen peptide composition for improving bone density according to claim 2, characterized in that: In step S3, the weight ratio of the ultrapure water to the chimaera is 1.3-1.6:1, and the weight ratio of the ultrapure water to the beef shank is 1.5-1.8:

1.

4. The collagen peptide composition for improving bone density according to claim 3, characterized in that: In step S4, the concentration of the sodium hydroxide solution is 3 mol / L.

5. The collagen peptide composition for improving bone density according to claim 4, characterized in that: In step 1, the mass fraction of glutathione in ultrapure water is 30-36%, and the mass fraction of dodecyl maltoside in ultrapure water is 32-43%.

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