A method for nutritional regulation of high activity of osteocytes and effective absorption of osteoblasts
Patent Information
- Application Number
- CN202611159157.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-08-01
- Publication Date
- 2026-09-29
AI Technical Summary
[0004]针对上述情况，为克服现有技术的缺陷，本发明提出的一种营养调控骨细胞高活性和成骨细胞有效吸收的方法，有效的解决了目前市场上骨营养补充靶向性差、吸收效率低、无法时序调控骨代谢、营养稳定性差、易出现血钙骤升、骨细胞活性维持效果差的问题
[0017]采用上述结构本发明取得的有益效果如下：本方案提出的一种营养调控骨细胞高活性和成骨细胞有效吸收的方法，通过制备纳米级羧化菊糖锶靶向缓释载体，结合多靶点复合营养配方，搭配梯度升温纳米喷雾干燥工艺制备核壳结构微胶囊，实现了骨营养的靶向递送、时序释放与精准调控；解决了传统骨营养产品吸收差、无靶向性、易血钙波动、调控效果单一的问题，分阶段实现肠道平稳吸收、成骨信号激活、骨代谢稳态维持，大幅提升成骨细胞营养吸收效率，长效维持骨细胞高活性，抑制破骨细胞异常增殖，骨营养利用率和骨代谢调控效果显著提升，且制剂稳定性强、生物相容性好，无代谢负担，适用范围广泛。
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of bone nutrition regulation biopreparation technology, specifically referring to a method for regulating the high activity of bone cells and the effective absorption by osteoblasts. Background Technology
[0002] Bone metabolic balance depends on the dynamic balance between osteoblast proliferation and differentiation, maintenance of osteoblast activity and inhibition of osteoclast activity. Decreased osteoblast activity, insufficient nutrient uptake by osteoblasts, and bone metabolism disorders are the core causes of bone problems such as osteoporosis, bone loss, and slow bone repair.
[0003] Most bone nutrition supplements and regulatory methods currently on the market have many shortcomings. Traditional bone nutrition supplements often use a combination of single nutrient components, which results in problems such as non-targeted nutrient release and low absorption efficiency. After oral administration, a sudden increase in blood calcium is likely to occur, which not only reduces nutrient utilization but also easily causes metabolic burden on the body. They cannot achieve time-sequential delivery and precise regulation of bone nutrition. Nutrient components cannot be specifically enriched at osteoblast sites, making it difficult to effectively activate osteogenic signaling pathways, maintain long-term high activity of osteoblasts, or effectively inhibit the excessive proliferation of osteoclasts, and thus cannot fundamentally regulate bone metabolic homeostasis. Summary of the Invention
[0004] In response to the above situation and to overcome the shortcomings of the existing technology, this invention proposes a method for regulating the high activity of bone cells and the effective absorption of osteoblasts through nutrition. This method effectively solves the problems of poor targeting, low absorption efficiency, inability to regulate bone metabolism in a timely manner, poor nutritional stability, easy occurrence of sudden increase in blood calcium, and poor maintenance of bone cell activity in current bone nutrition supplements on the market.
[0005] The technical solution adopted in this invention is as follows: This invention proposes a method for regulating the high activity of osteoblasts and the effective absorption of nutrients by osteoblasts, comprising the following steps:
[0006] S1. Preparation of targeted sustained-release nutrient carrier: Carboxylated inulin and strontium salt coordination reaction were used to prepare carboxylated inulin and strontium sustained-release complex as a targeted delivery carrier for nutrient components;
[0007] S2. Configuring a multi-target active nutrient composition: Marine oligopeptides, fat-soluble vitamin synergists, plant polyphenol antioxidant regulators, and trace mineral elements are compounded in proportion to obtain a bone-regulating active nutrient base solution.
[0008] S3. Sequential coating and curing: Using a gradient temperature nano-spray drying process, the active nutrient base liquid is loaded onto the surface and pores of the carboxylated inulin strontium sustained-release carrier to form a core-shell structured bone nutrient microcapsule formulation.
[0009] S4. In vivo time-series regulation intervention: Through oral delivery, utilizing the intestinal-targeted absorption and cell-targeted enrichment characteristics of the carrier, the bone cell activity is activated in stages, the osteoblasts are efficiently absorbed by nutrients, and the bone metabolism homeostasis is regulated.
[0010] Preferably, the preparation method of the carboxylated inulin strontium sustained-release complex in step S1 is as follows: inulin is mixed with citric acid and sodium bicarbonate in a mass ratio of 5:2:1, and the mixture is stirred in a warm water bath for carboxylation modification. After modification, it is coordinated with strontium chloride solution in a neutral buffer system, purified by dialysis, and then freeze-dried under vacuum to obtain a sustained-release carrier with a particle size of 50-200 nm.
[0011] To better achieve targeted sustained release and biocompatibility, the active nutrient composition in step S2 includes, by weight: 15-25 parts Antarctic krill oligopeptide, 8-15 parts hydrolyzed fish bone collagen tripeptide, 0.1-0.3 parts vitamin D3, 0.05-0.15 parts vitamin K2, 0.5-1.2 parts quercetin, 30-40 parts calcium, 5-8 parts magnesium, and 1-3 parts zinc. The synergistic combination of these components can regulate osteoblast metabolism through multiple targets, including nutrient supply, antioxidant regulation, and osteogenic activation, thereby improving osteoblast absorption efficiency.
[0012] To achieve stable encapsulation and long-lasting release of nutrients more quickly, the gradient temperature nano-spray drying process parameters in step S3 are as follows: inlet air temperature 120-140℃, middle section heat preservation temperature 80-90℃, outlet air temperature 40-50℃, and feed rate 5-8mL / min. This process prepares core-shell microcapsules with a particle size of 200-500nm, with the core as the carrier and the active nutrient component as the shell. The gradient temperature process avoids the destruction of the bioactivity of the active nutrient component by high temperature, ensuring the stability of the formulation.
[0013] Furthermore, the temporal regulation mechanism in step S4 is divided into three stages, which can achieve precise, long-term, and orderly bone metabolism regulation in vivo.
[0014] To achieve stable absorption and precise activation of bone formation, the first stage of the time-series regulation is intestinal-targeted slow-release absorption, which can effectively avoid a sudden increase in blood calcium, reduce the metabolic burden on the human body, and improve the intestinal absorption and utilization rate of nutrients.
[0015] Furthermore, the second stage of temporal regulation is osteoblast membrane-targeted enrichment, which can precisely activate the intracellular ERK1 / 2 osteogenic signaling pathway and rapidly enhance osteoblast activity and nutrient uptake capacity.
[0016] Furthermore, the third stage of temporal regulation is a long-term homeostatic regulation that can maintain high osteocyte activity for a long time while inhibiting excessive osteoclast proliferation, thereby achieving dynamic balance of bone metabolism.
[0017] The beneficial effects achieved by the present invention using the above structure are as follows: The proposed method for regulating the high activity of osteoblasts and the effective absorption of nutrients by osteoblasts involves preparing a nanoscale carboxylated inulin strontium-targeted sustained-release carrier, combining it with a multi-target composite nutrient formula, and using a gradient temperature nano-spray drying process to prepare core-shell microcapsules. This achieves targeted delivery, time-sequential release, and precise regulation of bone nutrition. It solves the problems of poor absorption, lack of targeting, easy fluctuation of blood calcium, and single regulatory effect of traditional bone nutrition products. It achieves stable intestinal absorption, activation of osteogenic signals, and maintenance of bone metabolism homeostasis in stages, significantly improving the nutrient absorption efficiency of osteoblasts, maintaining high osteoblast activity for a long time, inhibiting abnormal proliferation of osteoclasts, and significantly improving the utilization rate of bone nutrients and the regulatory effect of bone metabolism. Moreover, the formulation has strong stability, good biocompatibility, no metabolic burden, and a wide range of applications. Attached Figure Description
[0018] Figure 1 This is a schematic diagram of the process flow for a method for regulating the high activity of osteoblasts and the effective absorption of nutrients by osteoblasts proposed in this invention.
[0019] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof. Detailed Implementation
[0020] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.
[0021] Example 1: Preparation of Optimal Process Parameters
[0022] like Figure 1 As shown, the present invention proposes a method for regulating the high activity of osteoblasts and the effective absorption of nutrients by osteoblasts, comprising the following preparation and regulation steps:
[0023] S1. Preparation of targeted sustained-release nutrient carrier: 50 g inulin, 20 g citric acid, and 10 g sodium bicarbonate were uniformly mixed, and 500 mL deionized water was added. The mixture was placed in a 45°C water bath and stirred continuously for 35 min to complete the carboxylation modification of inulin. The modified carboxylated inulin was dispersed in a neutral phosphate buffer system, and 0.5 mol / L strontium chloride solution was slowly added dropwise. The mixture was stirred at a constant temperature for 3 h to complete the coordination reaction. After the reaction, the mixture was purified by dialysis for 12 h to remove unreacted impurities. Then, it was freeze-dried under vacuum to obtain a carboxylated inulin-strontium sustained-release complex with a particle size of 60 nm, which was used as a targeted nutrient delivery carrier.
[0024] S2. Preparation of a multi-target active nutrient composition: Accurately weigh 20g of Antarctic krill oligopeptide, 12g of hydrolyzed fish bone collagen tripeptide, 0.2g of vitamin D3, 0.1g of vitamin K2, 0.8g of quercetin, 35g of calcium, 6g of magnesium, and 2g of zinc according to the specified weight proportions. Dissolve each component in 800mL of sterile deionized water and stir at room temperature for 30min until completely dissolved to prepare a clear and stable bone-regulating active nutrient base solution.
[0025] S3. Sequential Coating and Curing: A gradient temperature nano-spray drying process is adopted, with the equipment inlet air temperature set at 130℃, the middle section insulation temperature at 85℃, and the outlet air temperature at 45℃, and the feeding rate adjusted to 6mL / min. The active nutrient base liquid is fed at a uniform rate, and the nutrient components are uniformly loaded onto the surface and internal pores of the carboxylated inulin strontium sustained-release carrier through spray drying. After curing, a core-shell structured bone nutrient microcapsule formulation with a particle size of 300nm, with the sustained-release carrier as the core and the active nutrient components as the shell, is obtained.
[0026] S4. In vivo temporal regulation intervention: The prepared bone nutrition microcapsule formulation was orally administered at a dose of 0.5 g / kg body weight daily for 8 weeks. Utilizing the intestinal-targeted absorption and osteocyte-targeted enrichment characteristics of the carboxylated inulin strontium carrier, a three-stage temporal regulation was achieved: The first stage is the intestinal-targeted sustained-release absorption stage, where the microcapsules slowly release nutrients in the intestine, avoiding the problem of a sudden increase in blood calcium caused by a large amount of nutrients absorbed instantaneously, ensuring stable nutrient absorption and improving intestinal absorption and utilization; the second stage is the osteoblast-targeted activation stage, where the carrier carries nutrients that are specifically enriched on the surface of osteoblast membranes, penetrating the cell membrane and activating the intracellular ERK1 / 2 osteogenic signaling pathway, significantly enhancing osteoblast activity and promoting the efficient uptake of minerals, peptides, and other nutrients by osteoblasts; the third stage is the long-term maintenance stage of bone metabolism homeostasis, where the carrier continuously releases active nutrients, maintaining high osteoblast activity for a long time, while simultaneously inhibiting excessive osteoclast proliferation through synergistic effects of the components, balancing osteogenic and osteoclast metabolic processes, and maintaining bone metabolic homeostasis.
[0027] Comparative Example 1: Traditional Single Calcium Supplementation Program
[0028] Ordinary calcium carbonate preparations were used, and the same dosage of calcium was administered daily. There was no carrier, no active nutrient compounding, and no sustained-release regulation. All other intervention conditions were completely consistent with those in Example 1.
[0029] Comparative Example 2: Common Peptide-Vitamin Complex
[0030] Using the same peptide, vitamin, and mineral formulation as in Example 1, without adding carboxylated inulin strontium sustained-release carrier, the formulation was prepared using a conventional stirring and mixing process and a high-temperature spray drying process, with the same dosage intervention.
[0031] Effect verification experiment
[0032] Sixty 3-month-old SPF-grade female SD rats were randomly divided into four groups: a control group, a control group 1, a control group 2, and the present invention group, with 15 rats in each group. An osteoporosis model was established using the ovariectomy method. After 8 weeks of continuous intervention, relevant indicators were measured. The experimental results are as follows:
[0033] 1. Osteoblast activity indicators: The osteoblast proliferation activity of the components of this invention was increased by 42.6% compared with the blank group, 31.2% compared with the control group, and 18.5% compared with the control group. The alkaline phosphatase (ALP) activity and osteocalcin (OCN) content were significantly higher than those of the control groups, indicating that it can effectively activate osteoblast activity.
[0034] 2. Nutritional absorption and utilization rate: The intestinal absorption and utilization rate of calcium in the group of this invention reached 89.3%, which is 27.8% higher than that of the traditional calcium supplementation group. There was no sudden increase in blood calcium. The enrichment rate of nutrient components in bone tissue was 35.1% higher than that of the ordinary compound group, and the specific absorption efficiency of osteoblasts was significantly improved.
[0035] 3. Bone metabolism homeostasis indicators: The number of osteoclasts in the present invention group was significantly reduced, the bone formation rate was greatly increased, the femoral bone mineral density was increased by 28.4% compared with the model group, and the number and thickness of trabeculae were significantly optimized, achieving a positive balance of bone metabolism.
[0036] 4. Safety indicators: During the intervention period, rats in each group experienced no gastrointestinal irritation or organ damage. The blood calcium and magnesium levels in the group of this invention were stable, and there were no abnormal mineral deposition. The safety of this invention is superior to that of traditional preparations.
[0037] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.
[0038] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.
[0039] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention; the actual structure is not limited thereto. In conclusion, if those skilled in the art are inspired by this description and design similar structures and embodiments without departing from the spirit of the invention, such designs should fall within the protection scope of the present invention.
Claims
1. A method for regulating the high activity of osteocytes and the effective absorption of nutrients by osteoblasts, characterized in that: Includes the following steps: S1. Preparation of targeted sustained-release nutrient carrier: Carboxylated inulin and strontium salt coordination reaction were used to prepare carboxylated inulin and strontium sustained-release complex as a targeted delivery carrier for nutrient components; S2. Configuring a multi-target active nutrient composition: Marine oligopeptides, fat-soluble vitamin synergists, plant polyphenol antioxidant regulators, and trace mineral elements are compounded in proportion to obtain a bone-regulating active nutrient base solution. S3. Sequential coating and curing: Using a gradient temperature nano-spray drying process, the active nutrient base liquid is loaded onto the surface and pores of the carboxylated inulin strontium sustained-release carrier to form a core-shell structured bone nutrient microcapsule formulation. S4. In vivo time-series regulation intervention: Through oral delivery, utilizing the intestinal-targeted absorption and cell-targeted enrichment characteristics of the carrier, the bone cell activity is activated in stages, the osteoblasts are efficiently absorbed by nutrients, and the bone metabolism homeostasis is regulated.
2. The method for regulating the high activity of osteoblasts and the effective absorption of nutrients according to claim 1, characterized in that: The preparation method of the carboxylated inulin strontium sustained-release complex in step S1 is as follows: inulin, citric acid and sodium bicarbonate are mixed at a mass ratio of 5:2:1, and the mixture is stirred in a warm water bath for carboxylation modification. After modification, it is coordinated with strontium chloride solution in a neutral buffer system. After dialysis purification, it is freeze-dried under vacuum to obtain a sustained-release carrier with a particle size of 50-200 nm.
3. The method for regulating the high activity of osteoblasts and the effective absorption of nutrients according to claim 1, characterized in that: The active nutrient composition in step S2 comprises, by weight, 15-25 parts Antarctic krill oligopeptide, 8-15 parts hydrolyzed fish bone collagen tripeptide, 0.1-0.3 parts vitamin D3, 0.05-0.15 parts vitamin K2, 0.5-1.2 parts quercetin, 30-40 parts calcium, 5-8 parts magnesium, and 1-3 parts zinc. The synergistic combination of these components can regulate osteoblast metabolism through multiple targets, including nutrient supply, antioxidant regulation, and osteogenic activation, thereby improving osteoblast absorption efficiency.
4. The method for regulating the high activity of osteoblasts and the effective absorption of nutrients according to claim 1, characterized in that: The gradient temperature nano-spray drying process parameters in step S3 are as follows: inlet air temperature 120-140℃, middle section heat preservation temperature 80-90℃, outlet air temperature 40-50℃, and feed rate 5-8mL / min. Core-shell microcapsules with a particle size of 200-500nm are prepared, with the core as the carrier and the active nutrient component as the shell. The gradient temperature process can avoid the destruction of the bioactivity of the active nutrient component by high temperature and ensure the stability of the formulation.
5. The method for regulating the high activity of osteoblasts and the effective absorption of nutrients according to claim 1, characterized in that: The temporal regulation mechanism in step S4 is divided into three stages, which can achieve precise, long-term, and orderly bone metabolism regulation in vivo.
6. The method for regulating the high activity of osteoblasts and the effective absorption of nutrients according to claim 5, characterized in that: The first stage of the time-series regulation is intestinal targeted slow-release absorption, which can effectively avoid a sudden increase in blood calcium, reduce the metabolic burden on the human body, and improve the intestinal absorption and utilization rate of nutrients.
7. The method for regulating the high activity of osteoblasts and the effective absorption of nutrients according to claim 5, characterized in that: The second stage of the time-series regulation involves targeted enrichment of osteoblast membranes, which can precisely activate the intracellular ERK1 / 2 osteogenic signaling pathway and rapidly enhance osteoblast activity and nutrient uptake capacity.
8. The method for regulating the high activity of osteoblasts and the effective absorption of nutrients according to claim 5, characterized in that: The third stage of the temporal regulation is long-term homeostasis regulation, which can maintain high osteocyte activity for a long time, while inhibiting excessive osteoclast proliferation and achieving dynamic balance of bone metabolism.