A composition for increasing bone strength, and a method of preparing and using the same

Abstract

The application provides a composition for increasing bone toughness as well as a preparation method and application thereof, and belongs to the technical field of health products. Through the synergistic effect of cod collagen peptide and L-lysine-L-aspartate, the application significantly promotes the synthesis of bone organic matter and the crosslinking of collagen fibers, strengthens the elasticity and bending strength of the bone while supplementing the calcium source, and avoids the problem that the bone is excessively hardened and the brittleness is increased due to the simple calcium supplement. Meanwhile, the technology of hydroxypropyl-beta-cyclodextrin inclusion of oleuropein, phospholipid complex wrapping of quercetin and microencapsulation of oligosaccharide yeast organic selenium is adopted, so that the bioavailability and antioxidant stability of the active ingredients are greatly improved, and the bone density and toughness are improved.

Description

Technical Field

[0001] This invention relates to the field of health product technology, specifically to a composition for increasing bone toughness, its preparation method, and its application. Background Technology

[0002] Osteoporosis is a systemic condition characterized by a decrease in bone mass and changes in the microstructure of bone tissue, leading to increased bone fragility and decreased bone strength. Fractures can occur even with minimal or no trauma. As we age, the body's ability to absorb calcium declines, causing bone resorption to exceed the rate of bone formation, resulting in bone loss and ultimately osteoporosis.

[0003] Currently, the main methods for preventing and treating osteoporosis, besides increasing exercise and improving dietary nutrition, are supplementing with appropriate amounts of calcium. Existing calcium supplements include active calcium ions, calcium gluconate, calcium lactate, and calcium tablets. Most of these calcium supplements or health foods only focus on the calcium content of the product, neglecting the degree of absorption and utilization by the body. This results in a large supply of calcium but low absorption and utilization, making it difficult to achieve the desired therapeutic effect. At the same time, middle-aged and elderly people with osteoporosis often experience pain, inflammation, stiffness, swelling, deformity, and functional impairment in the joints of the hands, wrists, ankles, knees, hips, shoulders, and spine due to articular cartilage degeneration. Currently, most commercially available calcium supplements primarily increase bone density and hardness, but their effect on symptoms such as osteoarthritis and bone pain is limited.

[0004] Patent CN118716632A discloses a polypeptide composition for improving osteoporosis and increasing bone density, and its preparation method. The composition comprises the following components: 1-5 parts type I collagen, 5-20 parts bovine bone collagen peptides, 5-10 parts shiitake mushroom powder, 3-10 parts citric acid, 5-10 parts Bifidobacterium bifidum powder, 40-50 parts whey protein, 5-20 parts oligopeptide powder, 1-5 parts calcium compound, 1-5 parts complex vitamins, and 1-5 parts theaflavins. The high content of collagen peptides and the addition of calcium compounds in the polypeptide composition allow calcium to be deposited in the bones under the binding effect of collagen, enhancing bone toughness and hardness. Simultaneously, citric acid chelates with calcium, increasing the body's absorption rate of calcium, thereby improving osteoporosis and increasing bone density. This technical solution improves bone calcium absorption and enhances bone toughness and hardness. Summary of the Invention

[0005] Based on this, the purpose of this application is to provide a composition that increases bone toughness, thereby improving bone toughness and alleviating osteoporosis.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A composition for increasing bone toughness, comprising the following raw materials in parts by weight: 40-55 parts cod collagen peptides; 10-20 parts calcium source; 10-15 parts oyster shell powder; Oligosaccharides 3-5 parts; Olive bitter glycosides, 6-12 parts; 8-15 parts of L-lysine-L-aspartate salt; 3-5 parts of lacquer yellow pigment; 4-10 parts zinc citrate; 0.01-0.5 parts of organic selenium in yeast; 10-20 parts of hydroxypropyl-β-cyclodextrin 10-15 parts lecithin; Magnesium stearate 5-45 parts.

[0007] Preferably, the calcium source is any one or more of calcium carbonate, calcium gluconate, calcium citrate, calcium lactate, L-calcium lactate, calcium hydrogen phosphate, L-threonate calcium, calcium glycinate, calcium aspartate, calcium citrate malate, calcium acetate, calcium chloride, and tricalcium phosphate.

[0008] Preferably, the oligosaccharide is one or more of trehalose, fructooligosaccharide, galactooligosaccharide, stachyose, and isomaltulose.

[0009] Preferably, the particle size of the oyster shell powder is <0.2 mm.

[0010] Another object of the present invention is to provide a method for preparing a composition that increases bone toughness, comprising the following steps: (1) Oleuropein inclusion: Hydroxypropyl-β-cyclodextrin was dissolved in water and stirred to obtain a cyclodextrin solution; oleuropein was dissolved in anhydrous ethanol to obtain an oleuropein solution; under high-speed shearing, the oleuropein solution was slowly added dropwise to the cyclodextrin solution, and the ethanol was removed by rotary evaporation to obtain an inclusion suspension, which was then freeze-dried to obtain an oleuropein inclusion powder. (2) Preparation of lacquinone microcapsules: Lacquinone and lecithin were mixed and dissolved in anhydrous ethanol. After stirring evenly, the ethanol was removed by rotary evaporation to form a lacquinone-phospholipid complex film. Tert-butanol was added and stirred to dissolve. The film was then freeze-dried to obtain lacquinone microcapsules. (3) Preparation of yeast organic selenium microcapsules: Oligosaccharides and yeast organic selenium were mixed and stirred evenly, and then freeze-dried to obtain yeast organic selenium microcapsules; (4) Mix cod collagen peptides, calcium source, oyster shell powder, L-lysine-L-aspartate salt, add water and magnesium stearate for wet granulation, and dry to form a slow-release layer; (5) After mixing olive bitter glycoside inclusion complex powder, rosin microcapsules, yeast organic selenium microcapsules and zinc citrate, dry compression is performed on the sustained-release layer to form an immediate-release layer, thus obtaining a composition that increases bone toughness.

[0011] Preferably, in step (1), the volume ratio of hydroxypropyl-β-cyclodextrin to water in the cyclodextrin solution is 1:2; and in the oleuropein solution, the volume ratio of oleuropein to anhydrous ethanol is 1:2.

[0012] Preferably, the rotation speed of the high-speed shearing in step (1) is 8000-10000 rpm, and after the dripping is completed, the shearing continues for 20-30 minutes, and the temperature of the rotary evaporation is 20-30℃.

[0013] Preferably, the anhydrous ethanol in step (2) is 10 times the total volume of flavonoids and lecithin; the rotary evaporation temperature is 20-30℃.

[0014] Preferably, the amount of tert-butanol used in step (2) is 2-2.5 times the mass of the flavonoid-phospholipid complex film.

[0015] Preferably, the drying in step (4) is performed at 40-45°C until the moisture content is <5%. Preferably, the pressure of the dry tableting in step (5) is 10-12 kPa.

[0016] The present invention also provides an application of the composition for increasing bone toughness, which can be used to prepare a medicament for increasing bone toughness.

[0017] Compared with the prior art, the present invention has the following beneficial effects: The composition for increasing bone toughness provided by this invention significantly promotes the synthesis of bone organic matter and the cross-linking of collagen fibers through the synergistic effect of cod collagen peptides and L-lysine-L-aspartate. While supplementing calcium, it strengthens bone elasticity and bending strength, avoiding the problem of excessive bone hardening and increased brittleness caused by simple calcium supplementation. Simultaneously, the use of hydroxypropyl-β-cyclodextrin encapsulating oleuropein, phospholipid complex encapsulating rutin, and oligosaccharide microencapsulating yeast organic selenium significantly improves the bioavailability and antioxidant stability of the above-mentioned active ingredients, thereby increasing bone density and toughness.

[0018] In this invention, oleuropein, rutin, and organic selenium work together to exert anti-inflammatory and antioxidant effects, inhibiting excessive osteoclast activation and reducing synovial inflammation, effectively alleviating bone pain, stiffness, and mobility impairment caused by osteoarthritis or postmenopausal estrogen deficiency. The introduction of zinc citrate further activates osteoblast alkaline phosphatase activity, working in conjunction with oligosaccharides to regulate intestinal calcium absorption pathways, forming a triple bone protection mechanism of "promoting synthesis, inhibiting absorption, and aiding deposition." Furthermore, the double-layer tablet design allows for both rapid and sustained-release of the active ingredients in vivo, ensuring both rapid symptom relief and long-lasting bone protection. The composition is prepared using a mild and quality-controlled process, making it suitable for daily health maintenance and adjunctive treatment of osteoporosis in middle-aged and elderly individuals and bone loss in postmenopausal women. Detailed Implementation

[0019] This invention provides a composition for increasing bone toughness, comprising the following raw materials in parts by weight: 40-55 parts cod collagen peptides; 10-20 parts calcium source; 10-15 parts oyster shell powder; Oligosaccharides 3-5 parts; Olive bitter glycosides, 6-12 parts; 8-15 parts of L-lysine-L-aspartate salt; 3-5 parts of lacquer yellow pigment; 4-10 parts zinc citrate; 0.01-0.5 parts of organic selenium in yeast; 10-20 parts of hydroxypropyl-β-cyclodextrin 10-15 parts lecithin; Magnesium stearate 5-45 parts.

[0020] Preferably, the calcium source is any one or more of calcium carbonate, calcium gluconate, calcium citrate, calcium lactate, L-calcium lactate, calcium hydrogen phosphate, L-threonate calcium, calcium glycinate, calcium aspartate, calcium citrate malate, calcium acetate, calcium chloride, and tricalcium phosphate.

[0021] Preferably, the oligosaccharide is one or more of trehalose, fructooligosaccharide, galactooligosaccharide, stachyose, and isomaltulose.

[0022] Preferably, the particle size of the oyster shell powder is <0.2 mm.

[0023] Another object of the present invention is to provide a method for preparing a composition that increases bone toughness, comprising the following steps: (1) Oleuropein inclusion: Hydroxypropyl-β-cyclodextrin was dissolved in twice the volume of water and stirred to obtain a cyclodextrin solution; oleuropein was dissolved in twice the volume of anhydrous ethanol to obtain an oleuropein solution; under high-speed shearing (8000-10000 rpm), the oleuropein solution was slowly added dropwise to the cyclodextrin solution, and shearing was continued for 20-30 minutes. Ethanol was removed by rotary evaporation at 25-30℃ to obtain an inclusion suspension, and the oleuropein inclusion powder was obtained by freeze drying. (2) Preparation of lacquer flavonoid microcapsules: Lacquer flavonoid and lecithin were mixed and dissolved in 10 times the volume of anhydrous ethanol. After stirring evenly, the ethanol was removed by rotary evaporation at 20-30℃ to form a lacquer flavonoid-phospholipid complex film. 2-2.5 times the mass of the lacquer flavonoid-phospholipid complex film was added and stirred to dissolve. The film was then freeze-dried to obtain lacquer flavonoid microcapsules. (3) Preparation of yeast organic selenium microcapsules: Oligosaccharides and yeast organic selenium were mixed and stirred evenly, and then freeze-dried to obtain yeast organic selenium microcapsules; (4) Mix cod collagen peptides, calcium source, oyster shell powder, L-lysine-L-aspartate salt, add water and magnesium stearate for wet granulation, and dry at 40-45℃ until the moisture content is <5% to form a slow-release layer. (5) After mixing olive bitter glycoside inclusion complex powder, rosin microcapsules, yeast organic selenium microcapsules and zinc citrate, dry compression (10-12 kPa) is performed on the sustained-release layer to form an immediate-release layer, which is a composition that increases bone toughness.

[0024] In specific embodiments of the present invention, unless otherwise specified, all raw materials are commercially available. The methods described in the present invention, unless otherwise specified, are conventional methods in the art. Water and ethanol are solvents added during the preparation process. Tert-butanol serves as a co-solvent and lyophilization scaffold material, and is not an effective component of the composition.

[0025] The technical solution of the present invention will be described in detail below through examples and comparative examples: Example 1 A composition for increasing bone toughness, comprising the following raw materials in parts by weight: 50 portions of cod collagen peptides; 15 parts of calcium gluconate; 10 parts of oyster shell powder with a particle size <0.2mm; 5 parts trehalose; 10 parts of oleuropein; 10 parts of L-lysine-L-aspartate salt; 3 parts of lacquer yellow pigment; 4 parts zinc citrate; 0.2 parts of organic selenium in yeast; 13 parts of hydroxypropyl-β-cyclodextrin 14 parts lecithin; 20 parts magnesium stearate.

[0026] The preparation method of the composition for increasing bone toughness includes the following steps: (1) Oleuropein inclusion: Hydroxypropyl-β-cyclodextrin was dissolved in twice the volume of water and stirred to obtain a cyclodextrin solution; oleuropein was dissolved in twice the volume of anhydrous ethanol to obtain an oleuropein solution; under high-speed shearing (10000 rpm), the oleuropein solution was slowly added dropwise to the cyclodextrin solution, and shearing was continued for 30 minutes. Ethanol was removed by rotary evaporation at 25-30℃ to obtain an inclusion suspension, and the oleuropein inclusion powder was obtained by freeze drying. (2) Preparation of lacquer flavonoid microcapsules: Lacquer flavonoid and lecithin were mixed and dissolved in 10 times the volume of anhydrous ethanol. After stirring evenly, the ethanol was removed by rotary evaporation at 20-30℃ to form a lacquer flavonoid-phospholipid complex film. 2.5 times the mass of the lacquer flavonoid-phospholipid complex film was added and stirred to dissolve. The film was then freeze-dried to obtain lacquer flavonoid microcapsules. (3) Preparation of yeast organic selenium microcapsules: Oligosaccharides and yeast organic selenium were mixed and stirred evenly, and then freeze-dried to obtain yeast organic selenium microcapsules; (4) Mix cod collagen peptides, calcium source, oyster shell powder, L-lysine-L-aspartate salt, add water and magnesium stearate for wet granulation, and dry at 40°C until the moisture content is <5% to form a slow-release layer. (5) After mixing olive bitter glycoside inclusion complex powder, rosin microcapsules, yeast organic selenium microcapsules and zinc citrate, dry compression (12 kPa) is performed on the sustained-release layer to form an immediate-release layer, which is a composition that increases bone toughness.

[0027] Comparative Example 1 A composition for increasing bone toughness, with the same raw material composition as in Example 1. The difference between Comparative Example 1 and Example 1 is that the oleuropein in Comparative Example 1 is not included, and the relevant raw materials are added in step (5).

[0028] Comparative Example 2 A composition for increasing bone toughness, wherein the raw materials do not contain hydroxypropyl-β-cyclodextrin, and the difference between the preparation method of Comparative Example 2 and Example 1 is that the oleuropein in Comparative Example 2 is not included, and the relevant raw materials are added in step (5).

[0029] Comparative Example 3 A composition for increasing bone toughness, with the same raw material composition as in Example 1. The difference between Comparative Example 3 and Example 1 is that the lacquinone in Comparative Example 3 is not prepared into microcapsules, and the relevant raw materials are added in step (5).

[0030] Comparative Example 4 A composition for increasing bone toughness, the raw materials do not contain lecithin. The difference between the preparation methods of Comparative Example 4 and Example 1 is that Comparative Example 4 does not involve the preparation of a flavonoid-phospholipid complex film, and the relevant raw materials are added in step (5).

[0031] Comparative Example 5 A composition for increasing bone toughness, with the same raw material composition as in Example 1. The difference between Comparative Example 5 and Example 1 is that Comparative Example 5 does not prepare yeast organic selenium microcapsules, and the relevant raw materials are added in step (5).

[0032] Comparative Example 6 A composition for increasing bone toughness, with the same raw material composition as in Example 1. The difference between Comparative Example 6 and Example 1 lies in the preparation method. In Comparative Example 6, cod collagen peptides, calcium source, oyster shell powder, L-lysine-L-aspartate salt, oleuropein inclusion complex powder, rosin microcapsules, yeast organic selenium microcapsules, and zinc citrate are mixed, water and magnesium stearate are added, and wet granulation is carried out. The mixture is then dried at 40-45°C until the moisture content is <5%, directly obtaining the composition for increasing bone toughness.

[0033] Comparative Example 7 A composition for increasing bone toughness, with the same raw material composition as in Example 1, differs from Example 1 in that Comparative Example 7 does not involve inclusion of oleuropein, nor does it prepare rutin microcapsules and yeast organoselenium microcapsules; after mixing the raw materials, wet granulation is performed, and the mixture is dried at 40°C until the moisture content is <5%, thus forming a composition for increasing bone toughness.

[0034] Animal intervention experiments: Experimental animals: 4-week-old male C56BL / 6 mice, weighing (20±2)g.

[0035] Grouping and Feeding: 180 mice were acclimatized for one week (temperature 23±2℃, humidity 50±2%, light and dark alternation every 12 hours). After acclimatization, they were randomly divided into 9 groups (n=20) and samples were administered by gavage as follows: In the examples and comparative groups, the corresponding compositions were administered by gavage at a dose of 500 mg / kg daily, while the control group was administered a placebo by gavage. The gavage frequency was once a day, at approximately 10:00 AM each day, for 8 weeks.

[0036] Whole-body bone mineral density (BMD, mg / cm2) of the experimental mice was measured using dual-energy X-ray absorptiometry before administration of the drug via gavage (0w) and after the experiment (8w). The results are shown in Table 1. Table 1

[0037] As shown in Table 1, the compositions of Example 1 and the comparative example significantly increased the bone mineral density of experimental mice at 8 weeks compared to the control group, indicating a certain bone formation promoting effect. Among them, Example 1 had a more significant effect on increasing bone mineral density compared to the comparative example.

[0038] Calcium deficiency animal model experiment: Laboratory animals: 240 SPF-grade, 4-week-old female SD rats, divided into 12 groups (normal group, model group, calcium carbonate group, calcium citrate group, and 8 sample groups (Examples and Comparative Examples 1-7)). All animals were acclimatized for one week before the formal experiment. Except for the normal group, which was fed a normal maintenance diet, all other groups were fed a calcium-free diet. The calcium-free diet was purchased commercially.

[0039] Solution preparation: Calcium carbonate group: Calcium carbonate was prepared to a specified concentration using 0.5% CMC-Na and administered by gavage, freshly prepared and used daily; Calcium citrate group: Calcium citrate was prepared to a specified concentration using 0.5% CMC-Na and administered by gavage, freshly prepared and used daily; Sample group: The compositions of the present invention (Example 1 and Comparative Examples 1-7) were prepared to a specified concentration using 0.5% CMC-Na and administered by gavage, freshly prepared and used daily.

[0040] The normal control group (n=20) was fed a standard maintenance diet, while the other groups (n=20) were fed a calcium-free diet for 5 consecutive weeks, with free access to deionized water. After the normal control group completed its acclimatization period, it was administered the same volume of 0.5% CMC-Na by gavage once daily for 5 consecutive weeks, during which time it was fed a calcium-maintaining diet. After the model group, calcium carbonate group, calcium citrate group, and sample group completed their acclimatization period, they were administered the same volume of 0.5% CMC-Na, calcium carbonate suspension, calcium citrate suspension, and sample (the combination of Example 1 and Comparative Examples 1-7) suspension (at a dose of 500 mg / kg) by gavage once daily for 5 consecutive weeks, during which time they were fed a calcium-free diet.

[0041] Femoral tissue preservation: After blood collection, the skin of the rat's leg was cut open, and the femurs on both sides were completely dissected, removing the attached muscle tissue and ligaments. The biomechanical testing of the femoral tissue at three points of bending was performed according to patent CN120436329A, and the results are shown in Table 2. Table 2

[0042] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A composition for increasing bone toughness, characterized in that, Including the following parts by weight of raw materials: 40-55 parts cod collagen peptides; 10-20 parts calcium source; 10-15 parts oyster shell powder; Oligosaccharides 3-5 parts; Olive bitter glycosides, 6-12 parts; 8-15 parts of L-lysine-L-aspartate salt; 3-5 parts of lacquer yellow pigment; 4-10 parts zinc citrate; 0.01-0.5 parts of organic selenium in yeast; 10-20 parts of hydroxypropyl-β-cyclodextrin 10-15 parts lecithin; Magnesium stearate 5-45 parts.

2. The composition for increasing bone toughness according to claim 1, characterized in that, The calcium source is any one or more of calcium carbonate, calcium gluconate, calcium citrate, calcium lactate, L-calcium lactate, calcium hydrogen phosphate, L-threonate calcium, calcium glycinate, calcium aspartate, calcium citrate malate, calcium acetate, calcium chloride, and tricalcium phosphate.

3. The composition for increasing bone toughness according to claim 1, characterized in that, The oligosaccharide is one or more of trehalose, fructooligosaccharide, galactooligosaccharide, stachyose, and isomaltulose.

4. The method for preparing the composition for increasing bone toughness according to claim 1, characterized in that, Includes the following steps: (1) Oleuropein inclusion: Hydroxypropyl-β-cyclodextrin was dissolved in water and stirred to obtain a cyclodextrin solution; oleuropein was dissolved in anhydrous ethanol to obtain an oleuropein solution; under high-speed shearing, the oleuropein solution was slowly added dropwise to the cyclodextrin solution, and the ethanol was removed by rotary evaporation to obtain an inclusion suspension, which was then freeze-dried to obtain an oleuropein inclusion powder. (2) Preparation of lacquinone microcapsules: Lacquinone and lecithin were mixed and dissolved in anhydrous ethanol. After stirring evenly, the ethanol was removed by rotary evaporation to form a lacquinone-phospholipid complex film. Tert-butanol was added and stirred to dissolve. The film was then freeze-dried to obtain lacquinone microcapsules. (3) Preparation of yeast organic selenium microcapsules: Oligosaccharides and yeast organic selenium were mixed and stirred evenly, and then freeze-dried to obtain yeast organic selenium microcapsules; (4) Mix cod collagen peptides, calcium source, oyster shell powder, L-lysine-L-aspartate salt, add water and magnesium stearate for wet granulation, and dry to form a slow-release layer; (5) After mixing olive bitter glycoside inclusion complex powder, rosin microcapsules, yeast organic selenium microcapsules and zinc citrate, dry compression is performed on the sustained-release layer to form an immediate-release layer, thus obtaining a composition that increases bone toughness.

5. The method for preparing the composition for increasing bone toughness according to claim 4, characterized in that, In step (1), the volume ratio of hydroxypropyl-β-cyclodextrin to water in the cyclodextrin solution is 1:2; and the volume ratio of oleuropein to anhydrous ethanol in the oleuropein solution is 1:

2.

6. The method for preparing the composition for increasing bone toughness according to claim 4, characterized in that, In step (1), the high-speed shearing speed is 8000-10000 rpm. After the dripping is completed, continue shearing for 20-30 minutes. The temperature of rotary evaporation is 20-30℃.

7. The method for preparing the composition for increasing bone toughness according to claim 4, characterized in that, The anhydrous ethanol in step (2) is 10 times the total volume of rutin and lecithin; the rotary evaporation temperature is 20-30℃; The amount of tert-butanol used in step (2) is 2-2.5 times the mass of the flavonoid-phospholipid complex film.

8. The method for preparing the composition for increasing bone toughness according to claim 4, characterized in that, The drying process described in step (4) involves drying at 40-45℃ until the moisture content is <5%.

9. The method for preparing the composition for increasing bone toughness according to claim 4, characterized in that, The pressure of the dry tableting in step (5) is 10-12 kPa.

10. The application of the composition for increasing bone toughness according to claim 1, characterized in that, The composition can be used to prepare drugs that increase bone toughness.

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