Compositions for increasing bone density and uses thereof

Abstract

The application discloses a composition for improving bone density and application thereof, and belongs to the technical field of food. The composition is prepared by using 1,3-dioleic acid-2-palmitic acid triglyceride, osteonectin and oligosaccharide in combination, and through the interaction between the components, the absorption and utilization of each other are promoted, the growth and development of the bone of an infant in the growth period are improved, the bone mineral content and bone density are improved, the bone health is promoted, and the composition is safe and has no side effect. Through optimization of the types of the oligosaccharide, it is found that the combination of oligogalactose and 2'-fucosyllactose can better improve the growth and development of the bone of the infant in the growth period.

Description

Technical Field

[0001] This invention belongs to the field of food technology, specifically relating to compositions for improving bone density and their applications. Background Technology

[0002] The development of the human skeletal system is a relatively long, dynamic, and continuous process that begins in early embryonic development and continues until maturity. The basic mechanisms of bone formation are bone tissue formation and bone resorption. During bone tissue formation, osteoblasts first secrete collagen fibers and bone matrix, forming osteoid. After osteoid formation, matrix ossification is completed by the deposition of basal apatite, becoming bone tissue. Subsequently, new osteoblasts continue to form osteoid on the surface of the newly formed bone tissue.

[0003] Calcium salts are deposited and transformed into bone. This continuous process allows bone tissue to grow steadily during the embryonic period and postnatal growth and development. Osteoblasts secrete various osteocyte matrix proteins and control the mineralization process of the bone matrix. Therefore, the occurrence, proliferation, differentiation, and maturation of osteoblasts are closely related to normal bone growth and development; disruption of any of these processes can lead to bone growth disorders. 60% of mature bone weight is mineral, mainly composed of calcium salts. The amount of mineral deposited in bone is called bone mineral content. The bone mineralization process in the human skeleton parallels the increase in height. Therefore, most bone accumulation occurs during childhood and adolescence, especially in the first year after birth and during puberty, when the mineral deposition in the bone matrix is ​​greatest. After height growth stops, bone mineralization continues at a rate of 8.5% per year until peak bone mass is reached, around age 30. After reaching peak bone mass, bone formation and bone resorption remain in balance. With increasing age and endocrine changes, the rate of bone resorption increases, and bone mass decreases. Each person's peak bone mass at bone maturity is different, and a high peak bone mass can effectively prevent age-related bone calcium loss.

[0004] An increase in peak bone mass reduces the risk of developing osteoporosis later in life; a 10% increase in peak bone mass during growth can reduce the risk of osteoporotic fractures by 50%. Therefore, improving bone growth through breast milk and dietary nutrition in early life, especially during infancy, childhood, and adolescence, can play a significant role in bone health later in life. Increasing peak bone mass during growth is crucial for maintaining bone health in adolescents.

[0005] OPO structured fat (1,3-dioleic acid-2-palmitic acid triglyceride) is the main triglyceride in breast milk, accounting for about 12% of total triglycerides. Palmitic acid (16:0) is the main saturated fatty acid, most of which is esterified at the sn-2 position (middle), while oleic acid is the main unsaturated fatty acid, most of which is esterified at the sn-1, sn-3 bond position (outer side) of the triglyceride. This structured oil can enable infant formula to mimic the composition and structure of fat in breast milk. Structured triglycerides are synthesized by enzyme catalysis, which contains 17%-25% palmitic acid, of which more than 40% is esterified at the sn-2 position.

[0006] Studies (Journal articles: "Feeding premature newborn infants palmitic acid in amounts and stereoisomeric position similar to that of human milk: Effects on fat and mineral balance", Carnielli, V P et al., The American journal of clinical nutrition, 1995, pp1037-1042; "The clinical effect of a new infant formula in infants with constipation: a double-blind, randomized cross-over trial", Bongers M E J et al., Nutrition Journal, 2007, pp8-14) have shown that OPO has the effects of enhancing fatty acid and mineral absorption, reducing constipation, increasing bone strength, and reducing inflammation. Compared with infants fed with ordinary infant formula, infants fed with high-OPO-content formula have higher bone mineral absorption rate, lower stool hardness, and less saponification of fatty acids in stool, similar to breastfed infants in terms of bone mineral, stool hardness, and fatty acid saponification. The mechanism may be that: 1) OPO is easily digested by infants, which can promote the absorption of energy substances such as fatty acids by the body; 2) OPO can promote the absorption of fat by infants; 3) OPO can promote the absorption of minerals (K, Na, Al, P, Ca, Mg) and vitamins necessary for the growth of infants, promote the normal growth of the bones and brain of infants, and maintain the excitation of neuromuscular, the conduction of nerve impulses, and the normal beating of the heart.

[0007] And bone bridge protein (OPN, milk in the bone bridge protein is called milk bridge protein, LPN), oligosaccharide (2'-fucose lactose, 3'-fucose lactose, oligogalactose, etc.) as the effective active ingredient of breast milk, can also regulate the growth and development of infants.

[0008] Based on this, the application provides a composition for improving bone density, which uses 1,3-dioleic acid-2-palmitic acid triglyceride, bone bridge protein and oligosaccharide in combination, improves the growth and development of the bones of infants and young children during the growth period, improves bone density and promotes bone health through the mutual promotion between the components. SUMMARY

[0009] The application provides a composition for improving bone density and its application. The application uses 1,3-dioleic acid-2-palmitic acid triglyceride, bone bridge protein and oligosaccharide in combination, promotes the absorption and utilization of each other through the interaction between the components, improves the growth and development of the bones of infants and young children during the growth period, improves bone density and promotes bone health. And the effect can be further improved by optimizing the types of oligosaccharide.

[0010] To achieve the above-mentioned purpose, in a first aspect, the application provides a composition for improving bone density, comprising: 1,3-dioleic acid-2-palmitic acid triglyceride, bone bridge protein and oligosaccharide.

[0011] In a preferred embodiment, the mass ratio of 1,3-dioleic acid-2-palmitic acid triglyceride, bone bridge protein and oligosaccharide is 100-200:0.5-20:100, more preferably 100-200:0.5-10:100.

[0012] In a preferred embodiment, the oligosaccharide is oligogalactose and 2'-fucose lactose (2'-FL) in a mass ratio of 1-2:1.

[0013] In a preferred embodiment, the composition further comprises at least one of unsaturated fatty acid, vitamin, mineral, protein, fat, carbohydrate, functional additive.

[0014] In a preferred embodiment, the functional additive comprises at least one of folic acid, nicotinic acid, pantothenic acid, biotin, choline, inositol, taurine, L-carnitine, nucleotide.

[0015] In a preferred embodiment, the unsaturated fatty acid comprises at least one of docosahexaenoic acid, eicosatetraenoic acid, linolenic acid, alpha-linolenic acid.

[0016] In a preferred embodiment, the vitamins include at least one of vitamin A, vitamin D, vitamin E, vitamin K1, vitamin B1, vitamin B2, vitamin B6, vitamin B 12

[0017] In a preferred embodiment, the minerals include at least one of sodium, potassium, copper, magnesium, iron, zinc, manganese, calcium, phosphorus, iodine, chlorine, selenium.

[0018] In a preferred embodiment, the product is a food or a medicine.

[0019] In a preferred embodiment, the product is a food or a medicine.

[0020] In a preferred embodiment, the product includes a nutritional supplement, a solid beverage, milk powder.

[0021] In a preferred embodiment, the product includes a nutritional supplement, a solid beverage, milk powder.

[0022] In a preferred embodiment, the product is a food or a medicine.

[0023] The beneficial effects of the present application are:

[0024] 1. The present application uses 1,3-dioleic acid-2-palmitic acid triglyceride, osteonectin and oligosaccharide in combination, promotes the absorption and utilization of each component through the interaction between the components, improves the growth and development of the skeleton of infants during the growth period, increases the bone mineral content and bone density, and promotes the health of the skeleton.

[0025] 2. The present application optimizes the types of oligosaccharides, and finds that the use of galacto-oligosaccharide and 2'-fucosyllactose in combination can better improve the growth and development of the skeleton of infants during the growth period.

[0026] 3. The bone density increasing composition of the present application has no significant effect on the development of organs of mice, has no side effects, and is safe. DETAILED DESCRIPTION

[0027] The present application will be further described below in conjunction with specific embodiments, and the advantages and characteristics of the present application will become more apparent as the description proceeds. However, these embodiments are only exemplary and do not constitute any limitation on the scope of the present application. Those skilled in the art should understand that the details and forms of the technical solutions of the present application can be modified or replaced without departing from the spirit and scope of the present application, and such modifications and replacements all fall within the protection scope of the present application.

[0028] ​It is worth mentioning that the raw materials used in the present application are all ordinary commercially available products, and their sources are not specifically limited.

[0029] 1,3-dioleic acid-2-palmitic acid triglyceride (OPO): InFat type TM 7860, purchased from AAK SE;

[0030] Osteopontin (OPN): type OPN-10, purchased from Arla Foods Ingredients;

[0031] Galactooligosaccharide (GOS): type GOS, purchased from Royal FrieslandCampina, the Netherlands;

[0032] 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL), 6'-sialyllactose (6'-SL): purchased from Glycom.

[0033] Example 1-3 and Comparative Example 1-4 composition preparation

[0034] The composition formulations of Examples 1-3 and Comparative Examples 1-4 are shown in Table 1:

[0035] Table 1

[0036]

[0037] The raw materials were weighed according to the formulations in Table 1 and mixed uniformly to obtain the corresponding compositions.

[0038] Test Example

[0039] 1. Animal grouping and feeding

[0040] Animals: 4-week-old male C56BL / 6 mice, weighing 18-20g, provided by Shanghai Slac Laboratory Animal Limited Liability Company, license number: SCXK (Shanghai) 2017-0005.

[0041] Grouping and feeding: 64 four-week-old male C56BL / 6 mice were adaptively fed for one week (temperature 23±2℃, humidity 50±2%, light and dark alternation every 12 hours). Randomly divided into 8 groups, 8 in each group. After one week of adaptation, Examples 1-3 and Comparative Examples 1-4 were administered with corresponding compositions at a dose of 400mg / kg per day, and the control group was free to eat. The above gavage was performed once a day, from 9-11am every day, for 8 weeks.

[0042] 2. Whole body bone mineral density

[0043] The whole body bone mineral density (BMD, mg / cm2) of the mice was measured by dual-energy X-ray absorptiometry before (pre-intervention) and after (post-intervention) the intragastrical administration, and the results are shown in Table 2. 2

[0044] Table 2 Whole body bone mineral density of mice in each group

[0045]

[0046] Note: * means P < 0.05 compared with pre-intervention; ** means P < 0.01 compared with pre-intervention; # means P < 0.05 compared with the control group; ## means P < 0.01 compared with the control group; Δ means P < 0.05 compared with Example 1.

[0047] As shown in Table 2, the bone mineral density of the mice in the Example 1-3 groups was significantly increased after the intervention compared with before the intervention, and was significantly increased compared with the control group; the improvement in bone mineral density of Example 1 was significantly higher than that of the Comparative Example 1-4 groups. It can be seen that the specific type of oligosaccharide has a great influence on the improvement of bone mineral density, and the use of oligogalactose and 2'-fucosyllactose in combination can promote bone development and growth and has higher bone mineral density compared with 3'-fucosyllactose or 6'-sialyllactose.

[0048] 3. Body weight and organ weight

[0049] During the experiment, the body weight of the mice in each group was regularly monitored and analyzed; and after the experiment, the mice were sacrificed, and the relevant organ weights of the mice were measured, and the organ / body weight ratios (heart / body, liver / body, kidney / body, and spleen / body, unit: %) were calculated. The results are shown in Table 3.

[0050] Table 3 Organ / body weight ratio of mice in each group

[0051] Group Heart / body ratio Liver / body ratio Kidney / body ratio Spleen / body ratio Control group 0.52±0.036 5.11±0.352 1.23±0.070 0.44±0.019 Example 1 0.54±0.041 5.14±0.323 1.23±0.057 0.45±0.023 Example 2 0.54±0.052 5.12±0.316 1.24±0.066 0.45±0.017 Example 3 0.53±0.039 5.09±0.289 1.23±0.068 0.44±0.016 Comparative Example 1 0.52±0.047 5.10±0.322 1.25±0.074 0.47±0.025 Comparative Example 2 0.53±0.055 5.13±0.367 1.24±0.078 0.48±0.029 Comparative Example 3 0.52±0.040 5.15±0.381 1.23±0.064 0.47±0.026 Comparative Example 4 0.53±0.046 5.12±0.333 1.25±0.081 0.47±0.031

[0052] As shown in Table 3, the organ / body weight ratios of the mice in the Example 1-3 and Comparative Example 1-4 groups had little difference compared with the control group, and there was no significant difference. It can be seen that the compositions in the Example 1-3 and Comparative Example 1-4 groups had no side effects and had no adverse effects on the development of the mice.

[0053] 4. Bone mineral detection

[0054] During the body weight and organ weight experiment, after the mice were sacrificed, the femur bones of the hind limbs were separated, and the bone mineral (calcium + zinc + magnesium) content of the left hind limb metaphysis of the mice was measured by a two-dimensional scanning single-photon bone densitometer (BH-602, Beijing Nuclear Instrument Factory), and the unit was μg / g. The results are shown in Table 4. ​

[0055] Bone mineral content of each group in Table 4

[0056] Group Bone mineral content μg / g Control group 328.2±34.5 Example 1 391.3 ± 46.4 # ]] Example 2 386.1 ± 49.2 # ]] Example 3 383.5 ± 51.0 # ]] Comparative Example 1 341.6±38.9* Comparative Example 2 352.7±41.1* Comparative Example 3 347.8±40.5* Comparative Example 4 339.2±36.6*

[0057] Note: # Indicates P < 0.01 compared with the control group; * indicates P < 0.05 compared with Example 1.

[0058] As can be seen from Table 4, the mineral content in the bones of the mice in Examples 1-3 is significantly higher than that in the control group and the groups of Comparative Examples 1-5, indicating that the composition defined in the application is beneficial to increasing the mineral content in the bones. The increase in the mineral content in the bones is beneficial to promoting the growth of the bones and increasing the bone density.

[0059] In summary, the composition of the application is beneficial to increasing the bone mineral content and the bone density, improving the growth and development of the bones during the growth period of infants and young children, promoting the health of the bones, and is safe and has no side effects. Moreover, the specific type of oligosaccharide in the composition has a great influence on increasing the bone mineral content and improving the bone density, among which, 2'-fucosyllactose compared with 3'-fucosyllactose or 6'-sialyllactose, the use of galactooligosaccharides and 2'-fucosyllactose in combination can promote the growth and development of the bones, and has higher bone mineral content and bone density.

[0060] The scheme of the application is not only limited to the technical means disclosed by the above technical means, but also includes the technical scheme composed of any combination of the above technical features. The above is the specific implementation method of the application, it should be pointed out that for ordinary skilled in the art, without departing from the principles of the application, can make a number of improvements and refinements, these improvements and refinements also as the protection scope of the application.

Claims

1. A composition for increasing bone density, characterized by, consisting of 5.6 parts of 1,3-dioleic-2-palmitic triglyceride, 0.1 part of osteopontin, 2.4 parts of galacto-oligosaccharide and 1.6 parts of 2'-fucosyllactose; or consisting of 8.0 parts of 1,3-dioleic-2-palmitic triglyceride, 0.4 part of osteopontin, 2.0 parts of galacto-oligosaccharide and 2.0 parts of 2'-fucosyllactose; or consisting of 3 parts of 1,3-dioleic-2-palmitic triglyceride, 0.03 part of osteopontin, 2.0 parts of galacto-oligosaccharide and 1.0 part of 2'-fucosyllactose.

2. Use of the composition for improving bone density according to claim 1 in the preparation of a product for promoting bone development.

3. Use according to claim 2, wherein the compound is ###0002### The promoting bone development is improving bone density.

4. The use according to claim 2, wherein The product is a health product or a medicine.

5. The use according to claim 2, wherein the compound is ###0002### The product includes a nutritional supplement or a solid beverage.

6. A product for promoting bone development, characterized by, The composition for improving bone density according to claim 1 is included.

Images