Application of resistant dextrin in preparation of product for preventing and improving osteoporosis
By using resistant dextrin or its composition in osteoporosis treatment, the high cost and side effects of existing drugs are solved, and the effect of safe and harmless improvement and treatment of osteoporosis is achieved.
Patent Information
- Application Number
- CN202510190630.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-20
- Publication Date
- 2025-04-25
AI Technical Summary
Existing drugs for treating osteoporosis are expensive and long-term use can produce multiple toxic side effects, resulting in the search for safer and harmless treatments becoming the focus of research.
resistant dextrin or resistant dextrin-containing compositions are used in the preparation of products that prevent and improve osteoporosis, including functional foods, pharmaceuticals or health foods.
By improving bone microstructure, increasing bone density and bone strength, inhibiting osteoclast activity, balancing bone metabolism, it significantly improves weight abnormalities and osteoporosis caused by estrogen deficiency, and has no toxicity and side effects.
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Figure CN119867325A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the field of development of new uses of food raw materials, and particularly relates to the use of resistant dextrin in preparing products for preventing and improving osteoporosis. Background Art
[0002] Osteoporosis (OP) is a chronic degenerative bone disease. Patients experience a decrease in overall bone mass, deterioration of bone microstructure, increased bone brittleness, and an increased risk of fractures. According to the cause of the disease, osteoporosis can be divided into primary osteoporosis and secondary osteoporosis. Among them, postmenopausal osteoporosis is a type of primary osteoporosis. It is a disease caused by a decrease in estrogen levels, which causes bone resorption activity to be far greater than bone reconstruction activity, leading to bone loss. According to statistics, about 1 / 3 of postmenopausal women aged around 50-70 years old suffer from osteoporosis. More than 80% of women over 80 years old suffer from osteoporosis. The probability of middle-aged and elderly women suffering from osteoporosis after menopause is significantly higher than that of men. Therefore, the treatment of postmenopausal osteoporosis is a top priority.
[0003] Bones are the supporting structure of the human body and one of its most important organs, performing multiple functions, including support and protection, movement, and blood production. There are many types of cells in the bones, among which osteoblasts and osteoclasts are closely related to bone metabolism. Bone homeostasis is a dynamic balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption under physiological conditions. When bone homeostasis is unbalanced, osteoclast activity increases, and bone resorption will be greater than bone reconstruction, leading to osteoporosis. Therefore, the key to treating osteoporosis lies in regulating bone reconstruction or inhibiting bone resorption to maintain a balanced bone homeostasis.
[0004] There are many drugs used clinically to treat osteoporosis, with bisphosphonates being a common option. They can inhibit bone resorption and help improve osteoporosis. Alendronate sodium is one of the most common bisphosphonates. Its chemical composition is 4-amino-1-mercaptobutylene, a trihydrate compound of sodium bisphosphonate that inhibits osteoclast differentiation and, therefore, bone resorption. However, these drugs are either expensive or have numerous toxic side effects with long-term use. For example, high doses of estrogen-based drugs can stimulate uterine cells and cause uterine lesions. Oral use of bisphosphonates can cause gastrointestinal disturbances such as nausea and vomiting. Therefore, finding safer and more harmless methods to improve and treat osteoporosis has become a research priority. Summary of the Invention
[0005] In view of the above problems, the purpose of the present invention is to provide a safe and harmless substance that can prevent, improve and treat osteoporosis, so as to solve the problems of existing osteoporosis treatment drugs being expensive and having side effects.
[0006] To achieve the above objectives, the present invention first provides the use of resistant dextrin or a composition containing resistant dextrin in the preparation of products for preventing and improving osteoporosis.
[0007] In one embodiment of the present invention, the osteoporosis includes osteoporosis caused by decreased estrogen levels, including senile osteoporosis and postmenopausal osteoporosis, preferably postmenopausal osteoporosis.
[0008] In one embodiment of the present invention, the improving osteoporosis includes improving bone microstructure and increasing bone strength.
[0009] In one embodiment of the present invention, improving bone microstructure includes improving trabecular network structure.
[0010] In one embodiment of the present invention, improving the trabecular network structure includes increasing bone density and bone volume fraction, increasing trabecular connection density, trabecular number and trabecular thickness, and reducing trabecular separation.
[0011] In one embodiment of the present invention, said increasing bone strength comprises increasing the stiffness and flexibility of the skeleton.
[0012] In one embodiment of the present invention, the product includes functional food, medicine or health food.
[0013] In one embodiment of the present invention, the functional food comprises at least one of a functional beverage, a functional granule, a functional biscuit and a functional capsule.
[0014] In one embodiment of the present invention, the medicine includes a drug for preventing and treating osteoporosis.
[0015] In one embodiment of the present invention, the health food includes a health food for increasing bone density.
[0016] The invention also discloses a health food composition for increasing bone density, wherein the composition comprises resistant dextrin.
[0017] The invention also discloses a pharmaceutical composition for preventing and treating osteoporosis, wherein the composition comprises resistant dextrin.
[0018] In one embodiment of the present invention, the composition further comprises at least one of corn starch, maltodextrin, soy protein, whey protein, calcium carbonate, inulin and oligofructose.
[0019] Beneficial effects:
[0020] 1. Resistant dextrin is processed from starch. It is a low-calorie glucan obtained by industrially extracting and refining the indigestible components of roasted dextrin. It is a low-molecular-weight, water-soluble dietary fiber. As a low-calorie, soluble food ingredient, it is widely used in the food industry. Using resistant dextrin for the prevention and improvement of osteoporosis offers advantages such as readily available raw materials, low cost, and safety.
[0021] 2. Resistant dextrin itself is a dietary fiber, widely used in the food industry. It is non-toxic and does not produce toxic side effects. In addition to being used as dietary fiber to improve body weight, it can also significantly improve abnormal weight gain caused by estrogen deficiency and reduced fat metabolism rate.
[0022] 3. The present invention has demonstrated through animal experiments that resistant dextrin helps improve the abnormal weight gain of mice caused by estrogen deficiency, improves bone density and trabecular reticular structure, improves the bone microstructure of ovariectomized mice, inhibits osteoclast activity, and balances bone metabolism.
[0023] 4. The present invention has demonstrated through animal experiments that resistant dextrin affects the levels of bone metabolism-related indicators in serum, indicating that it maintains normal bone metabolism by inhibiting the activity of bone resorption in ovariectomized mice. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] Figure 1 Schematic diagram of animal experiments.
[0025] Figure 2 Uterine index and serum estradiol levels in different groups of mice after 10 weeks of gavage with the test substance. Data are expressed as mean ± SD. Statistical significance was assessed using one-way analysis of variance followed by the Tukey test. Different letters indicate significant differences between groups.
[0026] Figure 3 The effect of gavage of different test substances on weight gain in mice. Data are expressed as mean ± SD. Statistical significance was assessed using a one-way analysis of variance followed by a Tukey test. Different letters indicate significant differences between groups.
[0027] Figure 4 Visceral indices of mice in different groups after 10 weeks of gavage with the test substance. Data are expressed as mean ± SD. Statistical significance was assessed using a one-way analysis of variance followed by a Tukey test. Different letters indicate significant differences between groups.
[0028] Figure 5 These are the bone microstructure images of mice in different groups after 10 weeks of gavage with the test substance, where A is the Micro-CT image of the trabecular structure of the distal femur, B is the HE staining image of the trabecular structure of the distal femur, and C is the TRAP staining image of the trabecular structure of the distal femur.
[0029] Figure 6 Figure 3. Bone mineral density (BMD), bone volume fraction (BV / TV), trabecular connectivity (COnn.D), trabecular number (Tb.N), trabecular thickness (Tb.Tn), and trabecular separation (Tb.S) at the soft end of the femur in different groups of mice after 10 weeks of gavage with the test substance. Data are expressed as mean ± SD. Statistical significance was assessed using one-way analysis of variance followed by the Tukey test. Different letters indicate significant differences between groups.
[0030] Figure 7 The concentrations of BGP, BALP, Cath-K, and TRACP in the serum of different groups of mice were measured 10 weeks after gavage with the test substance. Data are expressed as mean ± SD. Statistical significance was assessed using one-way analysis of variance followed by Tukey's test. Different letters indicate significant differences between groups.
[0031] Figure 8 Figure 1 shows bone stiffness and deflection values in different groups of mice after 10 weeks of gavage with the test substance. Data are expressed as mean ± SD. Statistical significance was assessed using a one-way analysis of variance followed by a Tukey test. Different letters indicate significant differences between groups. DETAILED DESCRIPTION
[0032] The following embodiments are merely some of the embodiments of the present invention, rather than all of them. Therefore, the detailed description of the embodiments of the present invention provided below is not intended to limit the scope of the claimed invention, but rather merely represents selected embodiments of the present invention. All other embodiments derived by those skilled in the art based on the embodiments of the present invention without creative effort are intended to fall within the scope of protection of the present invention.
[0033] 1. Reagents
[0034] The mice used in the examples of the present invention were 8-week-old female C57BL / 6J mice, SPF grade, weighing 18-20 g, purchased from Sibeifu (Suzhou) Experimental Animal Technology Co., Ltd.; resistant dextrin was purchased from Shanghai Bomeifeike Chemical Technology Co., Ltd.; Alendronate sodium (Alendronate, abbreviated as ALN) was purchased from Shanghai Titan Technology Co., Ltd.; BALP and E2 ELISA detection kits were purchased from Shanghai Enzyme-Linked Biological Technology Co., Ltd.; BGP, TRACP, and CTSK ELISA detection kits were purchased from Eliruite Biotechnology Co., Ltd.; anhydrous ethanol, xylene, and neutral resin were purchased from Sinopharm Chemical Reagent Co., Ltd.; hematoxylin-eosin (H&E) high-definition constant staining kit, environmentally friendly dewaxing and transparent solution, TRAP staining solution set, hematoxylin staining solution, differentiation solution, and blueing solution were purchased from Servicebio; immunohistochemistry pen was purchased from Vector.
[0035] 2. Test methods
[0036] 1. Mouse model construction
[0037] This study was approved by the Animal Ethics Committee of Jiangnan University with the ethics number JN.No20240530c0801010
[273] . Sixty SPF-grade female C57BL / 6J mice were housed in an environment with a temperature of 23±2℃, a humidity of 50±10%, a light cycle of 12h day and 12h dark cycle, and the mice were free to eat and drink during the study. After one week of adaptive feeding, they were randomly divided into a sham operation group (Sham group, 10 mice) and a surgery group (50 mice). After anesthesia, the mice in the surgery group underwent bilateral ovariectomy, while the mice in the sham operation group underwent bilateral ovariectomy with a small amount of fat removed from both ovaries, 3-4 drops of penicillin sodium were dripped, and the wounds were sutured in two layers. Penicillin sodium was injected for three consecutive days after surgery to prevent infection.
[0038] Three days after surgery, the mice in the surgery group were divided into the following groups according to their body weight: model control group (OVX), alendronate sodium group (ALN, 1 mg·kg -1 bw -1 ), resistant dextrin group (resistant dextrin, 2.25 g·kg -1 bw -1 ), inulin group (resistant dextrin, 2.25 g·kg -1 bw -1 ), oligofructose group (resistant dextrin, 2.25 g·kg -1 bw -1 ), 10 rats in each group. The Sham group and OVX group were gavaged with normal saline, and the ALN group, resistant dextrin group, inulin group, and oligofructose group were gavaged with the test substances at corresponding doses, such as Figure 1 The mice were gavaged once a day for 10 consecutive weeks, and their body weights were measured once a week.
[0039] At the end of the 10-week experiment, mice were weighed, blood was collected from the eyeballs, and serum was obtained by centrifugation at 5000×g for 15 minutes at 4°C. The serum was then stored at -80°C to avoid repeated freezing and thawing. The right femur of the mice was removed and fixed in 4% paraformaldehyde. The right tibia of the mice was removed and wrapped in saline-soaked gauze and stored at -20°C. The remaining femurs and tibias were placed in liquid nitrogen and stored at -80°C. Organs such as the liver, kidneys, spleen, and uterus were removed and weighed, and organ indices were calculated.
[0040] 2. Micro-CT Scanning
[0041] The distal end of the right femur was scanned using Micro-CT. The scanning conditions were: voltage 90 kV, current 88 μA, FOV 86 μm, high-resolution scanning mode, scanning time 4 min, and image and data analysis using the instrument's own software.
[0042] 3. Determination of serum-related indicators
[0043] After the serum was thawed, the levels of E2, BALP, TRACP-5B, BGP, and CTSK in mouse serum were determined using ELISA kits according to the instructions.
[0044] 4. Determination of bone biomechanical properties
[0045] The bone biomechanical properties of the right tibia of mice were determined using a physical property analyzer. The maximum load of the right tibia was determined using a three-point bending test. A shear probe was selected with a cross-plate spacing of 16 cm. The probe was located directly above the middle of the tibia at a moving rate of 1 mm / s.
[0046] 5. Bone histomorphometric determination
[0047] Hematoxylin-eosin staining (HE) was used to observe bone microstructure: the right femur was fixed in 4% paraformaldehyde solution, decalcified with 8% ethylenediaminetetraacetic acid (EDTA) for two weeks, embedded in paraffin, and cut into thin slices of about 2 μm to obtain paraffin sections. These sections were placed in a 60°C environment and baked for 60 minutes. After baking, staining was performed. The staining steps were as follows: soak in an environmentally friendly dewaxing solution twice for 20 minutes each time, then treat with anhydrous ethanol, 95% ethanol, and 75% ethanol for 5 minutes respectively, and wash with tap water. Then immerse in hematoxylin staining solution for 3 minutes and wash with tap water. Differentiation was performed using differentiation solution, washed with tap water, blued with bluing solution, and rinsed with running water. The sections were dehydrated in 95% ethanol for 1 min, immersed in eosin staining solution for 15 s, treated with 75% ethanol, 95% ethanol and anhydrous ethanol for 2 min in sequence, and finally transparentized with xylene for 2 min, sealed with neutral gum and allowed to dry.
[0048] Tartrate-resistant acidphosphatase (TRAP) staining was used to observe osteoclasts. The staining steps were as follows:
[0049] 1. Incubation solution configuration:
[0050] Mix TRAP Dye Solution B and TRAP Dye Solution C in equal proportions and use immediately. Label this solution as Solution B. Dissolve 20 mg of TRAP Dye Solution D in 1 mL of TRAP Dye Solution E and label this solution as Solution C. (Prepare Solution C at least 3 days in advance.)
[0051] Mix 18mL TRAP dye solution A + 1mL solution B + 1mL solution C, then add 0.282g TRAP dye solution F, dissolve it completely, filter it and set aside to make TRAP incubation solution.
[0052] 2. TRAP staining:
[0053] The sections were placed in environmentally friendly dewaxing and clearing solution twice for 20 minutes each, then treated with anhydrous ethanol, 95% ethanol, and 75% ethanol for 5 minutes each, and washed three times with distilled water. Next, a circle was drawn around the section with an immunohistochemistry pen. The sections were then placed in a humidified chamber and incubated in distilled water at 37°C for 2 hours. After the sections were incubated, the distilled water was decanted and filtered TRAP incubation solution was added dropwise. The sections were incubated at 37°C in the dark for 20 minutes. The incubation solution was decanted and the sections were washed with water. The nuclei were counterstained with hematoxylin for 15 seconds. The sections were dehydrated with 75% ethanol, 95% ethanol, and anhydrous ethanol for 2 minutes each, and finally, the sections were cleared with xylene for 2 minutes and mounted with neutral gum. The staining results showed that the cytoplasm of osteoclasts appeared red, while the nuclei appeared blue.
[0054] Example 1
[0055] Effects of resistant dextrin on toxicity and abnormal weight gain in ovariectomized mice.
[0056] Ovariectomy will cause a rapid decrease in estrogen levels in mice, so a decrease in serum estradiol levels can be used as a sign of successful model construction. Figure 2 It can be seen that compared with the Sham group, the serum estradiol content and uterine index of the OVX group mice were significantly lower than those of the Sham group, indicating that the model was successful. At the same time, compared with the Sham group, the OVX group mice gained more weight. This is because estrogen deficiency easily leads to fat accumulation in the abdomen, and the intervention of resistant dextrin can alleviate this weight gain ( Figure 3 The liver, spleen, and kidneys are important internal organs of the human body. Regardless of the disease being treated, the side effects of drugs on these organs should be kept within a reasonable range to avoid causing secondary damage to the body. Figure 4 The organ index can indicate that the intervention substances used have little toxicity and side effects and high safety performance in mice.
[0057] Example 2
[0058] Effects of resistant dextrin on bone microstructure in ovariectomized mice
[0059] 3D image of the bone microstructure of the distal femur of a mouse Figure 5 As shown in A, the trabecular reticular structure of mice in the Sham group was intact and tightly connected, while the number of trabeculae in mice in the OVX group was reduced and the reticular structure was severely damaged. After the intervention of resistant dextrin, the bone microstructure of the trabeculae was improved and the reticular structure was partially restored. The femoral microstructure of mice in different groups was analyzed using Micro-CT, and the following results were obtained: Figure 6 The data shown is from Figure 6 It can be seen that compared with the Sham group, the bone density BMD, bone volume fraction BV / TV, trabecular connectivity COnn.D, trabecular number Tb.N, trabecular thickness Tb.Tn, and trabecular separation Tb.Sp of the OVX group mice showed significant changes. After feeding resistant dextrin, compared with the OVX group, except for the parameter Tb.Sp, the other parameters increased, indicating that resistant dextrin has an improving effect on the trabeculae of ovariectomized mice.
[0060] HE staining can further observe the changes in the microstructure of the distal femur of mice, such as Figure 5 As shown in B, compared with Sham, the trabecular network structure of mice in the OVX group was destroyed and fat vacuoles increased. After intervention with resistant dextrin, the trabecular network structure of mice was improved. At the same time, TRAP staining can be used to observe the number of osteoclasts, which are stained wine red ( Figure 5 C) After ovariectomy, the number of osteoclasts increased significantly. These changes were alleviated in the resistant amylin group, indicating that resistant amylin intervention can inhibit the increase in osteoclast number.
[0061] When the human body is at different ages or suffers from different bone metabolic diseases, the content of bone metabolism-related indicators in the blood and urine will change to varying degrees. Common bone metabolism-related indicators include alkaline phosphatase (ALP), osteocalcin (BGP), tartrate-resistant acid phosphatase-5b (TRACP-5b) and tissue protein K (CTSK). Among them, ALP and BGP are substances secreted during the differentiation and mineralization of osteoblasts. They are mainly used to regulate bone reconstruction, and their content can reflect the activity of osteoblasts. Osteoclast-related markers such as TRACP-5b and CTSK are mainly used to regulate the process of bone resorption and verify the activity of osteoclasts. Figure 7 The contents of bone metabolism indicators in the serum of mice in different groups are shown. Figure 7 It can be seen that resistant dextrin can alleviate the abnormal changes of various indicators caused by osteoporosis, indicating that resistant dextrin treatment has a balancing effect on the bone metabolism of the experimental group, and resistant dextrin has a greater impact on osteoclasts.
[0062] Example 3
[0063] Effects of resistant dextrin on bone strength in ovariectomized mice
[0064] The stiffness and flexibility of bones can reflect bone strength, such as Figure 8 As shown in the data, compared with the Sham group, the bone stiffness and flexibility of OVX mice were significantly decreased, and improved to a certain extent after intervention with resistant dextrin. These results indicate that resistant dextrin can improve the damaged bone microstructure and increase bone strength.
[0065] The embodiments provided above are not intended to limit the scope of the present invention, nor are the steps described to limit their execution order. Any obvious improvements to the present invention made by those skilled in the art in combination with existing common knowledge shall fall within the scope of protection defined by the claims of the present invention.
Claims
1. Use of resistant dextrin or a composition containing resistant dextrin in preparing products for preventing and improving osteoporosis.
2. The use according to claim 1, characterized in that: The osteoporosis includes osteoporosis caused by decreased estrogen levels, including senile osteoporosis and postmenopausal osteoporosis.
3. The use according to claim 1, characterized in that: The improvement of osteoporosis includes improving bone microstructure and increasing bone strength.
4. The use according to claim 3, characterized in that: The improving of bone microstructure includes improving the trabecular network structure.
5. The use according to claim 4, characterized in that: The improvement of the trabecular network structure includes increasing bone density and bone volume fraction, increasing trabecular connection density, trabecular number and trabecular thickness, and reducing trabecular separation.
6. The use according to claim 3, characterized in that: The increasing bone strength includes increasing the stiffness and flexibility of the bone.
7. The use according to claim 1, characterized in that: The product includes functional food, medicine or health food, the functional food includes at least one of functional beverage, functional granules, functional biscuits and functional capsules, the medicine includes drugs for preventing and treating osteoporosis, and the health food includes health food for increasing bone density.
8. A health food composition for increasing bone density, characterized in that: The composition comprises resistant dextrin and at least one of corn starch, maltodextrin, soy protein, whey protein, calcium carbonate, inulin and oligofructose.
9. A pharmaceutical composition for preventing and treating osteoporosis, characterized in that: The composition comprises resistant dextrin.
10. The composition according to claim 9, characterized in that The composition further comprises at least one of corn starch, maltodextrin, soy protein, whey protein, calcium carbonate, inulin and oligofructose.