CN116098201A - Use of nutritional compositions for improving bone density and bone metabolism - Google Patents
Use of nutritional compositions for improving bone density and bone metabolism Download PDFInfo
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- CN116098201A CN116098201A CN202310378093.0A CN202310378093A CN116098201A CN 116098201 A CN116098201 A CN 116098201A CN 202310378093 A CN202310378093 A CN 202310378093A CN 116098201 A CN116098201 A CN 116098201A
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- acetylneuraminic acid
- bone
- hyaluronate
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- 235000015927 pasta Nutrition 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
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- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
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- 239000011591 potassium Substances 0.000 description 1
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- 239000004224 potassium gluconate Substances 0.000 description 1
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- 229960003189 potassium gluconate Drugs 0.000 description 1
- 229960004839 potassium iodide Drugs 0.000 description 1
- 235000007715 potassium iodide Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229960002847 prasterone Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
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- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
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- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000015067 sauces Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
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- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
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- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 description 1
- MVHOXPMVPRDZIH-CBSHMQKXSA-M sodium N-[(3S,4R,5R,6S,7R)-1-carboxy-3,5,6,7,8-pentahydroxy-1-oxooctan-4-yl]ethanimidate Chemical compound [Na+].CC(=O)N[C@H]([C@@H](O)CC(=O)C([O-])=O)[C@@H](O)[C@H](O)[C@H](O)CO MVHOXPMVPRDZIH-CBSHMQKXSA-M 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 229960001462 sodium cyclamate Drugs 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000011781 sodium selenite Substances 0.000 description 1
- 235000015921 sodium selenite Nutrition 0.000 description 1
- 229960001471 sodium selenite Drugs 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 229940071440 soy protein isolate Drugs 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940034610 toothpaste Drugs 0.000 description 1
- 239000000606 toothpaste Substances 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 235000001019 trigonella foenum-graecum Nutrition 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 235000021119 whey protein Nutrition 0.000 description 1
- 235000008939 whole milk Nutrition 0.000 description 1
- 239000011670 zinc gluconate Substances 0.000 description 1
- 235000011478 zinc gluconate Nutrition 0.000 description 1
- 229960000306 zinc gluconate Drugs 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/152—Milk preparations; Milk powder or milk powder preparations containing additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/16—Agglomerating or granulating milk powder; Making instant milk powder; Products obtained thereby
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to the use of a nutritional composition for improving bone density and bone metabolism, said composition comprising: i) N-acetylneuraminic acid, ii) hyaluronate; wherein the composition has an N-acetylneuraminic acid to hyaluronate ratio of greater than 1:4 and optionally also comprises other nutritional ingredients.
Description
Technical Field
The invention belongs to the field of foods, relates to application of a nutritional composition, and in particular relates to application of a health care or nutritional composition in improving bone density and bone metabolism.
Background
Bone is a high-activity connective tissue, can repair self microdamage through bone metabolism and bone remodeling, keeps the homeostasis balance of bone structure, load and calcium content, and is also used as an endocrine organ to regulate and control metabolic process, thus being an important organ for maintaining human life. Bone comprises an extracellular protein matrix (osteoid) in which bone cells are interspersed, and mineral components consisting of calcium salts and other minerals are located within the extracellular matrix. Bone undergoes remodeling during resorption, in which case the bone is degraded by osteoclasts and then replaced (reformed) by osteoblasts. The occurrence of remodeling regulates calcium homeostasis, repairs routinely stress damaged bones, and shapes bones as they grow or as the mechanical stress pattern changes. Osteoclasts degrade bone in a specific area and then undergo apoptosis. Osteoblasts remodelle new bone and mediate its remineralization. During remineralization, some osteoblasts become entrapped within the calcified material and then become bone cells. Osteoporosis is a systemic bone metabolic disease, caused by a variety of factors, and is characterized by deterioration of bone mass, bone density and microstructure of bone tissue, increased bone fragility, and susceptibility to fracture. Osteoporosis has severely threatened human health, eventually leading to reduced patient daily activities, reduced quality of life, and increased mortality.
N-acetylneuraminic acid (N-acetylneuraminic acid, neu5 Ac) is known as one of the most common sialic acids, an amino monosaccharide derivative having a 9-carbon skeleton, which is widely present in mammalian tissues, mainly in a bound form or in a free form of oligosaccharide, glycoprotein or glycolipid, or the like. The human brain tissue and the breast milk have rich Neu5Ac content, and the Neu5Ac level in the breast milk is 0.25-1.50 g/L, and the Neu5Ac is also present in foods such as milk, milk products, livestock meat, eggs and the like. N-acetylneuraminic acid has been shown to have important significance for various biological functions in vivo in recent years, and modern medicine considers that N-acetylneuraminic acid is related to various diseases, such as tumor, cancer, coronary heart disease, diabetes and the like. A series of important sugar medicines developed by taking N-acetylneuraminic acid as raw materials have very good effects on antivirus, anti-tumor, anti-inflammation and treating senile dementia. In addition, in multiple countries, N-acetylneuraminic acid is obtained as a new food raw material, and unsuitable people are not specified, so that the N-acetylneuraminic acid can be used in dairy products.
Hyaluronic acid and its salt are physiologically active substances widely existing in human bodies, and have a regulating effect on physiological functions of human bodies. Sodium hyaluronate (Sodium Hyaluronate, SH) is a sodium salt form of Hyaluronic Acid (HA), which constitutes a major component of connective tissue such as human cell matrix, vitreous humor, joint synovial fluid, and the like. The disaccharide unit composed of N-acetylglucosamine and D-glucuronic acid is taken as a basic unit, and the linear polysaccharide is repeatedly formed. The linear polysaccharide chains are continuously bent and wound to form irregular linear molecular configuration. Each HA molecule consists of 25-10000 disaccharide units, with HA molecular weight range 10000 ～ 4000000. The sodium hyaluronate in the joint synovial fluid has high viscoelasticity, plays a role in shock absorption and lubrication protection of joint cartilage, and can form a protective barrier on the surface of the joint cartilage. The articular cartilage is composed of a substance such as proteoglycan containing sodium hyaluronate, which imparts a specific porosity and elasticity to cartilage and plays an important role in maintaining the integrity of cartilage tissue. In addition, sodium hyaluronate is also available as a new resource food in multiple countries, and can be applied to milk and dairy products.
Although some experimental results show that hyaluronate has an efficacy of promoting joint/bone health, studies on the application of both in foods and the like are insufficient; and studies on the function of N-acetylneuraminic acid have been mainly focused on improving brain development, delaying skin aging, antiviral, etc., such as:
the cited document 1 discloses a composition containing sodium hyaluronate and a preparation method thereof, wherein the sodium hyaluronate is compounded to be used as a main component, and amino acid, vitamin, mineral elements and complexes thereof, protein, glucosamine, sodium chondroitin sulfate and the like are matched, so that the composition integrates calcium supplementing and joint protection, has good prevention effect on arthritis and joint movement damage, and simultaneously can promote development, enhance bone density and improve toughness and hardness of bones.
Reference 2 discloses the use of N-acetylneuraminic acid monomer, N-acetylneuraminic acid hydrate or N-acetylneuraminic acid salt in personal care products, which utilizes the effects of inhibiting bacteria, promoting cell repair and the like of N-acetylneuraminic acid and applies the N-acetylneuraminic acid to personal care products such as toothpaste, mouthwash, eye drops, bath lotion and the like.
Reference 3 discloses the use of N-acetylneuraminic acid derived from E.coli fermentation in foods, wherein N-acetylneuraminic acid exists in the form of N-acetylneuraminic acid monomer, N-acetylneuraminic acid hydrate or N-acetylneuraminic acid salt, is safe and nontoxic, has own metabolic pathway in human body, has the functions of participating in cell membrane, resisting viruses and promoting neurodevelopment.
The citation 4 discloses a whitening anti-aging medicament and a production method thereof, which mainly intervenes in the formation of skin melanin through glutathione, fenugreek powder and L-cysteine, and is helpful for delaying skin aging through collagen peptide, evening primrose extract and red algae powder, and the formula also comprises soybean lecithin, dehydroepiandrosterone, sodium hyaluronate, N-acetylneuraminic acid, additives and the like, wherein the mass ratio of the sodium hyaluronate is 5.5% -6.5%, and the mass ratio of the N-acetylneuraminic acid is 2% -4%.
Despite the above studies, there is still room for further research and development in terms of developing a new food product that is beneficial to human bone health and bone development, especially to improve bone density and bone metabolism, and to increase the absorption of phosphorus in the blood, calcium in the bone.
Citation literature:
citation 1: CN109965104A
Citation 2: CN104586642A
Citation 3: CN104996986A
Citation 4: CN114470175A
Disclosure of Invention
Problems to be solved by the invention
As described above, sodium hyaluronate has been proposed in the art to have effects of improving bone density, protecting bone joints, preventing osteoporosis, and the like; the efficacy of N-acetylneuraminic acid in bacteriostasis, antivirus, promoting nerve development and the like is also proposed, and although cited document 4 uses sodium hyaluronate and N-acetylneuraminic acid as part of a pharmaceutical formulation, the effects are mainly reflected in delaying skin aging, and neither is used as a main component, and a plurality of other components are added. Thus, there is no further investigation in the prior art as to whether or not there is a synergistic effect between N-acetylneuraminic acid and hyaluronate, or in what way, especially as to whether or not there is a synergistic effect in promoting bone health.
Further, although the prior art does not suggest a positive effect on bone development and bone health for N-acetylneuraminic acid, the present invention has unexpectedly found that N-acetylneuraminic acid substances, when used in combination with hyaluronate, demonstrate synergistic improvements in bone density and bone metabolism, increase absorption of phosphorus in the blood and calcium in the bone, and thereby improve bone development and help maintain bone health.
Therefore, in view of the above-mentioned research situation in the prior art, the technical problem to be solved by the present invention is to provide a simple-composition, non-pharmaceutical nutritional composition for improving bone density and bone metabolism, the composition comprising N-acetylneuraminic acid substance and hyaluronate; when the two are used together, a synergistic effect can be obtained in improving bone density and bone metabolism. For example, under the cooperation of a certain amount of the components, the content of phosphorus and osteocalcin in serum and the content of calcium in bones can be obviously increased, the relative volume of bone density and trabecula is obviously increased, and the effect of reducing the level of alkaline phosphatase in serum and the like is shown, so that the components are beneficial to improving bone density and bone metabolism for people suffering from osteoporosis, are beneficial to bone health growth for healthy people and teenagers in growth and development, and can prevent osteoporosis and the like for adults, especially middle-aged and elderly people.
Solution for solving the problem
Through long-term researches of the inventor, the technical problems can be solved through the following technical scheme:
[1] use of a nutritional composition in the manufacture of an edible product for improving bone density and bone metabolism, wherein the composition comprises:
i) N-acetylneuraminic acid substances are used for preparing the medicine,
ii) hyaluronate;
wherein the dosage ratio of the N-acetylneuraminic acid substances to the hyaluronate in the composition is more than 1:4; and, optionally, the composition also includes other nutritional ingredients.
[2] The use according to [1], wherein the N-acetylneuraminic acid substance is present in one or more forms of N-acetylneuraminic acid anhydrate, N-acetylneuraminic acid hydrate or N-acetylneuraminic acid salt.
[3] The use according to [1] or [2], wherein the composition has an amount ratio of the N-acetylneuraminic acid substance to the hyaluronate of 5:1 or less.
[4] The use according to [1] or [2], wherein the N-acetylneuraminic acid substance is selected from one or more of natural raw material extract, chemical synthesis, enzyme catalysis or microbial fermentation broth; the hyaluronate is selected from one or more of animal extract, chemical synthesis or artificial fermentation broth.
[5] The use according to [1] or [2], wherein the content of the N-acetylneuraminic acid substance is 0.04% by mass or more based on the total mass of the composition; the content of the hyaluronate is 0.01% by mass or more.
[6] The use according to [1] or [2], wherein the ratio of the N-acetylneuraminic acid substance to the hyaluronate is 1:2 to 2:1.
[7] The use according to [1] or [2], wherein the other nutritional ingredients comprise one or more of proteins, vitamins, monosaccharides, polysaccharides or plant extracts; the composition is a liquid, semi-solid or solid.
[8] The use according to [1] or [2], wherein the edible product comprises a dairy product, and the dairy product comprises a pediatric dairy product, a maternal, middle aged and elderly dairy product.
ADVANTAGEOUS EFFECTS OF INVENTION
Through implementation of the technical scheme, the invention has the following advantages and can obtain the following technical effects:
1) The composition provided by the invention firstly provides that the N-acetylneuraminic acid substances and hyaluronate, especially sodium hyaluronate, are compounded to obtain a synergistic effect in the aspects of improving bone density and bone metabolism;
2) The invention provides the application of the nutritional composition in preparation of the nutritional composition for improving bone density and bone metabolism, the composition of the nutritional composition is simple and clear, the convenient compounding is facilitated, various foods are also facilitated to be conveniently added or prepared, the process and auxiliary material components are adjusted according to the actual application requirements, and the nutritional composition is processed into various foods, and is particularly suitable for preparing foods including milk powder products for middle-aged and elderly people;
3) The N-acetylneuraminic acid substances and the hyaluronate in the composition are in a safe dosage range, so that the composition can be used for a long time and is suitable for various unspecified people.
Detailed Description
The following describes the present invention in detail. The following description of the technical features is based on the representative embodiments and specific examples of the present invention, but the present invention is not limited to these embodiments and specific examples. It should be noted that:
in the present specification, the numerical range indicated by "numerical values a to B" means a range including the end point value A, B.
In the present specification, a numerical range indicated by "above" or "below" is a numerical range including the present number.
In the present specification, the meaning of "can" includes both the meaning of performing a certain process and the meaning of not performing a certain process.
In this specification, the use of "optional" or "optional" means that certain substances, components, steps of performing, conditions of applying, etc. may or may not be used.
As used herein, "child" means a population of human life that is older than 3 years of age and younger than 18 years of age or older than 18 years of age, but still in the growing stage.
In the present specification, "middle-aged and elderly" as used herein means a population of humans aged over 45 years.
As used herein, "room temperature" means the indoor ambient temperature of "23±2℃.
In the present specification, unit names used are international standard unit names, and "%" used represent weight or mass% unless otherwise specified.
In the present specification, the use of "substantially" means that the standard deviation from the theoretical model or theoretical data is within a range of 5%, preferably 3%, more preferably 1%.
Reference throughout this specification to "some specific/preferred embodiments," "other specific/preferred embodiments," "an embodiment," and so forth, means that a particular element (e.g., feature, structure, property, and/or characteristic) described in connection with the embodiment is included in at least one embodiment described herein, and may or may not be present in other embodiments. In addition, it is to be understood that the elements may be combined in any suitable manner in the various embodiments. The present invention provides a method comprising: i) Use of a nutritional composition of N-acetylneuraminic acid and ii) hyaluronate for the preparation of an edible product for improving bone density and bone metabolism, and optionally also including other nutritional ingredients, which composition exhibits a significant synergistic effect with one or more of the following functions or effects: can remarkably increase the contents of phosphorus element, osteocalcin and calcium in bones in serum, remarkably increase bone density and relative volume of bone trabeculae, reduce alkaline phosphatase level in serum and the like, is beneficial to improving bone density and bone metabolism, and has positive auxiliary protection effect on bone health of human bodies.
The technical scheme of the invention is mainly based on the following findings:
according to the invention, animal experiments are carried out to research the application of the composition obtained by compounding N-acetylneuraminic acid substances and hyaluronate according to a certain proportion, and based on the influence of the use of the composition on related indexes in rat serum and bones, the unexpected discovery that the use of the nutritional composition formed by compounding the N-acetylneuraminic acid substances and hyaluronate can improve bone density and bone metabolism, increase the absorption of phosphorus in blood and calcium in bones, and generate obvious synergistic effects in the aspects of assisting in protecting bone health and the like.
(N-acetylneuraminic acid substances)
In the present invention, N-acetylneuraminic acid substances are used as essential components.
N-acetylneuraminic acid (Neu 5 Ac), also known as sialic acid, is an acetylated derivative of acidic glyconeuraminic acid, has important roles in biological recognition, cellular immunity and disease, and is one of the most important monomers of sialylated human milk oligosaccharides (sialylated HMOs or sialyllactose). Neu5Ac has been widely approved as a new food material in various countries, allowed to be used as a food material, recommended food consumption of 500 mg/day or less, and not specified for unsuitable people.
The production method and source of the N-acetylneuraminic acid substance are not particularly limited, and may be one or more selected from natural raw material extracts, chemical synthesis, enzyme catalysis, microbial fermentation broth and the like. For extracts derived from natural sources, there may be mentioned: extracting from natural materials such as nidus Collocaliae, casein, ovum gallus Domesticus, milk, and blood plasma; for the production method of chemical synthesis, there may be mentioned: n-acetylmannosamine is taken as a starting material, can be decarboxylated under the catalysis of alkali to form N-acetylneuraminic acid, and can be obtained by indium catalysis and ozonolysis in acidic alcohol solution; for the enzyme catalysis method, there may be mentioned: catalyzing N-acetylmannosamine and sodium pyruvate to be converted into N-acetylneuraminic acid by N-acetylneuraminic acid aldolase; for fermentation broth derived from microorganisms, there may be mentioned: is prepared from food-grade glucose and corn steep liquor by fermenting with Escherichia coli (strain SA-8), filtering, sterilizing, hydrolyzing, and purifying. In some embodiments of the invention, N-acetylneuraminic acid can be prepared by itself or can be obtained commercially.
The present invention is not particularly limited with respect to the presence or use form of the N-acetylneuraminic acid substance, and may be present in one or more forms of N-acetylneuraminic acid anhydrate, N-acetylneuraminic acid hydrate or N-acetylneuraminic acid salt. Wherein, the N-acetylneuraminic acid hydrate can be N-acetylneuraminic acid dihydrate, the biological efficacy of which is basically consistent with that of the N-acetylneuraminic acid hydrate, except that the N-acetylneuraminic acid hydrate and the N-acetylneuraminic acid hydrate are slightly different due to the existence of crystal water in a solid state, and the two crystal water of dihydrate and the hydrogen bond connected with the N-acetylneuraminic acid are broken in a liquid state, so that the two properties are the same. In addition, N-acetylneuraminic acid salts may be used, and examples thereof include N-acetylneuraminic acid sodium salt, N-acetylneuraminic acid potassium salt and N-acetylneuraminic acid ammonium salt. The method for producing N-acetylneuraminic acid salt is not limited, and a solvent composed of ketones or alcohols may be added to an N-acetylneuraminic acid aqueous solution containing sodium, potassium or ammonium having a pH of 3.0 to 9.0 to precipitate crystals finally.
In some preferred embodiments of the invention, the N-acetylneuraminic acid can be used as is, as an aqueous solution, or with the aid of solvents acceptable for other food products.
(hyaluronate)
In the invention, hyaluronate is used as an essential component to be compounded with the N-acetylneuraminic acid substances so as to realize the technical effect of the invention. Among them, the kind of hyaluronate is not particularly limited in principle, and a metal salt or a mixture of a plurality of metal salts of usual hyaluronate may be used, and preferably, an alkali metal salt of hyaluronate, such as sodium salt (hereinafter also abbreviated as sodium hyaluronate), may be used.
Sodium hyaluronate, also known as sodium hyaluronate, is a dry product that is white granules or powder, free of malodor. The sodium salt of glycosaminoglycan is composed of D-glucuronic acid and N-acetyl-D-glucosamine disaccharide unit, and is a linear macromolecular polysaccharide. Sodium hyaluronate has been approved as a new food material in some countries or regions, for example, recommended food usage of less than or equal to 200 mg/day. Sodium hyaluronate is soluble in water to form a thick viscous elastic solution in water, and has physiological pH value and ionic strength. The molecular morphology of the modified polysaccharide is variable, and the modified polysaccharide belongs to a non-drug neutral medium.
The source of the sodium hyaluronate is not particularly limited in the invention, and glucose, yeast powder, peptone and the like can be used as culture media, and streptococcus equi subspecies zooepidemicus can be used as culture mediaStreptococcus equi subsp. zooepidemicus) The chicken is produced by fermentation, or can be extracted manually by the fermentation liquor of cockscomb. Since hyaluronic acid is commonly present in animals and humans, such as skin, muscle, cartilage, brain, cockscomb, arterial and venous walls, etc. Therefore, common extraction materials include cockscomb, umbilical cord, bullseye, etc.
Further, the mode of use of sodium hyaluronate in the present invention is not particularly limited, and it is preferable that sodium hyaluronate is prepared as an aqueous solution for use.
(synergistic effect)
In the prior art, the hyaluronate has been confirmed to have the effects of assisting in protecting the bone joint, damping, lubricating the articular cartilage and the like, while the N-acetylneuraminic acid substance has the verified effects mainly of regulating the development of the nervous system, being beneficial to the maintenance of brain functions, resisting tumors, whitening and the like in view of the clear biological activity mechanism thereof.
The invention discovers that when the two components are compounded, the obtained nutritional composition can synergistically improve the bone health condition, increase the absorption of phosphorus in blood and calcium in bones, and is particularly beneficial to synergistically improving bone density, bone metabolism and the like.
In some preferred embodiments of the present invention, the ratio of the N-acetylneuraminic acid to the hyaluronate may be greater than 1:4 by mass, preferably 1:3 or more, more preferably 1:2 or more, and most preferably 1:1 or more in terms of improving bone density and good bone metabolism efficacy, for example, (1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, etc.): more than 1. The upper limit of the ratio may be 5:1 or less, preferably 4:1 or less, or 3.5:1 or less, and more preferably 3:1 or less, for example, (2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3, 2.2, 2.1, etc.): 1 or less.
By matching the contents, the use amount of hyaluronate can be reduced, and under the cooperation of N-acetylneuraminic acid substances, the relatively low use amount of hyaluronate can also show the effects of improving bone density and bone metabolism and increasing the absorption of phosphorus in blood and calcium in bones.
(composition)
The nutritional composition of the present invention comprises at least the above-described N-acetylneuraminic acid and hyaluronate. The form of the composition is not particularly limited, and may be any of the above-mentioned extracts containing these components, artificial fermentation, chemical synthesis, and the like, or may be any of the two extracts having high purity.
In addition, other components or other nutritional ingredients which may be used in the composition of the present invention are not particularly limited, and other edible ingredients, food additives or solvent components and the like which are commonly used in the art may be used without impairing the effects of the present invention, and other nutritional ingredients include one or more of proteins, vitamins, monosaccharides, polysaccharides or plant extracts.
The nutritional composition of the present invention may be present in a liquid form or may be present in a semi-solid or solid form.
Further, animal experiments prove that the composition provided by the invention can obviously increase the contents of phosphorus element, osteocalcin and calcium in bones in serum, obviously increase the bone density and the relative volume of bone trabeculae, can reduce the alkaline phosphatase level in serum and the like, is beneficial to improving the bone density and the bone metabolism, and has positive auxiliary protection effect on the bone health of human bodies. Therefore, the product can be applied to a functional health product or a functional health additive to be used (eaten).
In addition, the amount of N-acetylneuraminic acid and hyaluronate (especially the highest amount) used in the use of the nutritional composition provided by the present invention is in principle not limited. However, in view of food safety regulations for different food types and the addition amounts of functional substances for different food types, in some specific embodiments, the content of the N-acetylneuraminic acid substance may be 0.04% by mass or more, preferably 0.08% by mass or more, 0.1% by mass or more, 0.15% by mass or more, 0.20% by mass or more, more preferably 0.25% by mass or more, and 1% by mass or less, preferably 0.95% by mass or less, more preferably 0.9% by mass or less, etc. in terms of securing a synergistic effect and use safety, based on the total mass of the composition; the content of the hyaluronate may be 0.01% by mass or more, preferably 0.07% by mass or more, more preferably 0.1% by mass or more, 0.20% by mass or more, still more preferably 0.25% by mass or more, and 1% by mass or less, preferably 0.95% by mass or less, still more preferably 0.9% by mass or less.
(edible products)
In some specific embodiments, the edible product may be a functional food, a health food, etc., and in particular, may be a food suitable for children, teenagers, pregnant women and middle-aged and elderly people in the growing up. The edible product may be obtained via the above-described nutritional composition or may be obtained by further processing the above-described nutritional composition.
The edible product of the present invention is not particularly limited, and may be a food in a liquid, semi-solid or solid form, and generally includes pasta, beverage, flushable food, baked goods, sauce or functional nutritional supplement food. In particular, the edible product of the invention is particularly suitable for children's milk powder products, middle-aged and elderly milk powder products.
For the edible product of the invention, in addition to or in addition to the above-described nutritional composition, optionally, the following components may be used or included:
juice of fruits or vegetables, or solid components thereof, etc.;
the functional vitamins and other functional ingredients may include, for example, white sugar, probiotics, sodium cyclamate, monosaccharides, polysaccharides or plant extracts, potassium sorbate, vitamin a, beta-carotene, vitamin D3, vitamin E, vitamin K1, vitamin B2, vitamin B6, vitamin B12, vitamin C, pantothenic acid, folic acid, nicotinic acid, choline, inositol, biotin, or the like;
a protein/peptide/amino acid component selected from at least one of whey protein powder, soy protein isolate, whole milk powder, whole egg powder, lactoferrin, bovine colostrum, amino acids, and protein peptides; and the amino acid is at least one selected from L-lysine-L-glutamic acid, L-arginine, L-tryptophan, L-glutamine, taurine, L-valine, L-isoleucine and L-leucine; the protein peptide is one or more selected from soybean oligopeptide, wheat protein peptide, silkworm chrysalis protein peptide, marine fish oligopeptide powder, cola peptide, amino peptide and ovalbumin peptide;
dietary fiber component comprising one or more of inulin, konjaku flour, galacto-oligosaccharide, fructo-oligosaccharide, isomalto-oligosaccharide, soy polysaccharide, cyclodextrin, resistant dextrin, and soy fiber;
the supplemental elemental components may be selected from metal ion salts of organic acids, such as one or more of calcium citrate, calcium L-lactate, calcium hydrogen phosphate, potassium gluconate, sodium citrate, ferrous gluconate, potassium iodide, zinc gluconate, sodium selenite, copper gluconate, chromium sulfate, manganese gluconate, and magnesium gluconate.
Examples
Hereinafter, the present invention will be further specifically described by way of specific examples. Unless specifically stated otherwise, the reagents, methods and apparatus employed in the present invention are those conventional in the art.
In the examples section below, the raw materials used are as follows, unless otherwise indicated.
Raw materials
Main reagent
N-acetylneuraminic acid, sodium hyaluronate, 1% sodium pentobarbital (Merck, germany) and rat Osteocalcin (OC) ELISA kit (ELK 2391) for deer (Wuhan) biotechnology Co., ltd
Main instrument and equipment
Small animal living body tomography imaging system (Mirabs, the Netherlands), one ten thousandth electronic balance (Beijing Sidolis instruments systems Co., ltd.), electric constant temperature water bath pot (Tianjin Lawster instruments Co., ltd.), refrigerator (Qingdao sea Co., ltd.), vortex oscillator (but Wo Suoke technology (Beijing Co., ltd.), centrifuge (Shanghai chemical machinery Co.), ultra-low temperature refrigerator (ThermoFisher Co., USA), full-automatic biochemical analyzer (Hitachi Biochemical incubator (SPX-150B-Z Shanghai Bo Hirship) plate washer (1575 BIO-RAD) enzyme-labeled instrument (VARIOSKAN FLASH Thermo)
Experimental animal
SD female (8 week old) SPF grade rats with stable health status were scheduled for 96. Feeding environment: the room temperature is 20-25 ℃, the lighting is dark and alternate every 12 hours, the relative humidity is about 50%, the feed, the drinking water and the like are uniformly matched, the indoor environment is kept well ventilated, the indoor environment is cleaned every day, and the good sanitary environment in the cage is maintained. Animal welfare: during the whole treatment process of the experiment, reasonable means are carried out on the rats, which accords with the relevant regulations of the ethical committee of experimental animals, and the treatment is specifically carried out according to IAC and other relevant standard operation regulations (SOP); the method for killing comprises the following steps: and (3) carrying out anesthesia on the rats after the experiment is finished and the rats are removed, carrying out bloodletting and sacrifice on the rats, then storing the cadavers in a special refrigerator container, and finally carrying out harmless unified treatment.
In the following sections, unless otherwise indicated, in referring to parts by mass of components in the nutritional composition and ratios, the parts by mass refer to parts by mass of N-acetylneuraminic acid, sodium hyaluronate as active ingredients, and the ratios refer to the mass ratio of N-acetylneuraminic acid, sodium hyaluronate as active ingredients.
Animal experiment
1. Experimental method
Rats were randomly divided into a control group (sham operation group) and a ovariectomized group according to body weight, and 6 rats were in a blank control group; the ovariectomized group of 90 rats was used to prepare a model of osteoporosis rats. The ovariectomized group 90 rats were sutured after removing the ovariectomy on both sides, the control group (sham operation group) was subjected to corresponding operations, and the sterilization treatment was performed after the operation was completed. On the 5 th day of modeling, the ovariectomized rats are randomly divided into 13 groups (1 group is a model group and the other 12 groups are experimental groups) according to the weight, different gastric lavage treatments are carried out, each rat is respectively subjected to gastric lavage according to the respective dosing amount, and the test objects are prepared into corresponding doses by adopting purified water; the comparative group and model group were subjected to gastric lavage with purified water, and the experimental groups (experimental examples 1 to 6 and comparative examples 1 to 6) were subjected to gastric lavage for 1 time per day with the composition and dosage of the group information according to the animal experiment shown in table 1, and each group of mice was subjected to gastric lavage for 12 weeks.
Table 1:
during the experiment, the body weight of each group of rats is periodically monitored and analyzed weekly, and the rats are sacrificed after the end, dissected and the related viscera weights are weighed.
2. Index detection
2.1 Method for measuring calcium content in bones
Taking out the left femur under aseptic condition, removing soft tissue, washing with sterile physiological saline, and storing in a refrigerator at-80deg.C. After the sample is crushed and is digested by nitric acid, the sample is atomized by atomic absorption flame, the absorbance is measured at 422.7nm, and the concentration is converted according to a standard curve.
2.2 Determination of phosphorus content in serum
Centrifuging the rat blood sample at 3000r/min for 15min, and preserving at-80deg.C. Taking the prepared serum supernatant, and measuring the phosphorus content in the serum by using a corresponding kit.
2.3 Bone mineral density determination
Rats were anesthetized with 1% sodium pentobarbital, fixed on a small animal biopsy tomography imager with a resolution of 20 μm, reconstructed images after scanning was completed, and analyzed for bone density by Inveon Research Workplace 2.2.2.2 software for each group.
Determination of index related to bone metabolism
2.4 Determination of alkaline phosphatase (ALP) content in serum
Centrifuging the rat blood sample at 3000r/min for 15min, and preserving at-80deg.C. And (3) taking the prepared serum supernatant, detecting the alkaline phosphatase (ALP) content index by using a corresponding kit, and strictly performing the operation steps according to the specification of the kit.
2.5 Determination of osteocalcin (BGP) content in serum
Centrifuging the rat blood sample at 3000r/min for 15min, and preserving at-80deg.C. And (3) taking the prepared serum supernatant, detecting the osteocalcin (BGP) content index by using a corresponding kit, and strictly performing the operation steps according to the specification of the kit.
2.6 Detection of relative trabecular volume (Tb. BV/TV)
Rats were anesthetized with 1% sodium pentobarbital, fixed on a small animal biopsy imager with a resolution of 20 μm, image reconstructed after the end of scanning, and each group of rat bone trabecular relative volumes (tb.bv/TV) were analyzed using Inveon Research Workplace 2.2.2.2 software.
2.7 Data analysis
Statistical analysis was performed on experimental data using SPSS 22.0 statistical software, and experimental results passed the variance alignment test using one-factor analysis of variance for statistical differences between groups, expressed as mean ± standard deviation (mean ± SD). P >0.05 represents no statistical significance, and P <0.05 is statistically significant.
3. Experimental results
3.1 Results of measurement of calcium (Ca) content in bones
To evaluate the effect of the test substances alone or in combination on the bone calcium content of rats, the bone calcium content of rats was measured as shown in Table 2-1.
Table 2-1:
note that: # representation and blank comparison, <0.05, ## representation and blank comparison, < 0.01, ### representation and blank comparison, < 0.001; * represents the comparison with the model control group, P is less than 0.05, ** represents the comparison with the model control group, P is less than 0.01, *** representing the comparison with the model control group, wherein P is less than 0.001; the following is the same.
3.2 Serum phosphorus (P) content detection result
To evaluate the effect of the treatment alone or in combination on the phosphorus content in the rat serum, the phosphorus content in the rat serum was measured as shown in tables 2-2.
Table 2-2:
calcium and phosphorus are the main elements that make up the skeleton, and coordinate with each other in the creation of the skeleton. The sample treatment results show that compared with a model control group, the contents of Ca and P in bones of experimental examples and comparative examples are improved to different degrees (the difference of the comparative examples is not obvious), and when N-acetylneuraminic acid and sodium hyaluronate are compounded and used in a certain proportion, the N-acetylneuraminic acid and the sodium hyaluronate can be coordinated with each other in the establishment of bones, and the absorption of Ca and P can be synergistically increased, so that the development and the health of bones are promoted.
By comparison of the experimental examples and the comparative examples, it was found that there was a synergistic effect of N-acetylneuraminic acid and sodium hyaluronate when used in combination, for example, in Table 2-1, experimental example 3 corresponds to the combination of comparative examples 2 and 6 in terms of the components used and the amounts used, and experimental example 3, comparative example 2 and comparative example 6 increased the Ca content in bones by 21.25mg/g, 4.85mg/g, 12.75mg/g, respectively, and the increase in Ca in bones of the rat of experimental example 3 (21.25 mg/g) was greater than the sum of the respective increases of comparative examples 2 and 6 (17.6 mg/g). Similarly, experimental example 5 (corresponding to the combination of comparative example 3 and comparative example 6) can also draw the conclusion of synergy.
In Table 2-2, experimental example 3 corresponds to the combination of comparative examples 2 and 6, and the amounts of P in the serum of Experimental example 3, comparative example 2 and comparative example 6 were increased by 0.17mM, 0.06 mM mM, 0.03mM, respectively, relative to the model control group, and the increment of P in the serum of the rat of Experimental example 3 (0.17 mM) was larger than the sum of the respective increments of comparative examples 2 and 6 (0.09 mM). Similarly, experimental examples 4, 5 and 6 also draw the conclusion of synergy.
3.3 Bone mineral density measurement results
To evaluate the effect of the test substances alone or in combination on the bone density of rats, the bone density of rats was measured as shown in tables 2 to 3.
Table 2-3:
sample treatment results show that when N-acetylneuraminic acid and sodium hyaluronate are used in a certain proportion in combination, skeletal development and health can be synergistically promoted, and bone density can be remarkably increased.
For example, experimental example 5 corresponds to a combination of comparative examples 3 and 6, and experimental example 5, comparative example 3, and comparative example 6 respectively increased bone density by 0.062g/cm, relative to the model control group 3 、0.03g/cm 3 、0.028g/cm 3 The increase in bone density of Experimental example 5 (0.062 g/cm) 3 ) Greater than the sum of the respective increments of comparative example 3 and comparative example 6 (0.058 g/cm) 3 ）。
Measurement results of index related to bone metabolism
3.4 Measurement of alkaline phosphatase (ALP) content in serum
To evaluate the effect of the treatment alone or in combination on alkaline phosphatase (ALP) content in rat serum, the ALP content in rat serum was measured as shown in tables 2 to 4.
Tables 2 to 4:
ALP is synthesized and secreted mainly by osteoblasts and liver, and is an important index reflecting bone metabolism. In serum 50% of ALP is produced by osteogenic secretion, and therefore serum ALP levels reflect, to some extent, changes in bone metabolism. The related research results show that when bone loss occurs rapidly in the body or fracture risk exists, the serum ALP level in the body is obviously increased, and the analysis of the serum ALP level may be caused by the aggravation of bone resorption, so that compensatory bone formation and bone conversion are enhanced.
The sample treatment results show that the N-acetylneuraminic acid and the hyaluronic acid have a synergistic effect when being combined in a certain proportion, can synergistically promote bone development and health, synergistically and obviously reduce the content of alkaline phosphatase in serum, and obviously improve bone metabolism.
For example, in terms of the components used and the amounts used, experimental example 3 corresponds to the combination of comparative examples 2 and 6, and experimental example 3, comparative example 2, comparative example 6 reduced alkaline phosphatase by 36.89U/L, 14.09U/L, 22.15U/L, respectively, relative to the model control group, and the decrease in alkaline phosphatase in rat serum (36.89U/L) in experimental example 3 was greater than the sum of the respective decreases (36.24U/L) of comparative example 2 and comparative example 6. This conclusion was also reached in experimental example 6.
3.5 Determination of the osteocalcin (BGP) content in serum
To evaluate the effect of the treatment alone or in combination on the osteocalcin (BGP) content in rat serum, BGP in rat serum was measured as shown in tables 2-5.
Tables 2-5:
osteocalcin (BGP) is a non-collagen protein containing vitamin-dependent amino acids, and is mainly produced and secreted by osteoblasts, and it can maintain the normal mineralization rate of bone, inhibit abnormal hydroxyapatite crystal formation and cartilage mineralization rate, and can directly reflect the functional state of osteoblasts and the condition of bone formation.
The results of sample treatment show that when the two components are used in combination in a certain ratio, the content of osteocalcin in rat serum can be synergistically increased to promote bone metabolism.
With respect to the components used and the amounts used, experimental example 3 corresponds to the combination of comparative examples 2 and 6, and experimental example 3, comparative example 2, comparative example 6 increased the BGP content in the rat serum by 0.41 μg/L, 0.02 μg/L, 0.19 μg/L, respectively, and the BGP increment (0.41 μg/L) in experimental example 5 was greater than the sum of the respective increments (0.21 μg/L) of comparative examples 2 and 5, respectively, with respect to the model control group.
Experimental examples 2 (corresponding to the combination of comparative example 3 and comparative example 5), 4 (corresponding to the combination of comparative example 3 and comparative example 5), 5 (corresponding to the combination of comparative example 3 and comparative example 6), and 6 (corresponding to the combination of comparative example 2 and comparative example 5) all gave conclusions about the synergy.
Therefore, when the two components are combined in a certain proportion, the content of osteocalcin in serum can be obviously increased, and a specific proportion between the two components has a synergistic effect, so that bone metabolism can be synergistically improved, and bone health can be promoted.
3.6 Detection of relative trabecular volume (Tb. BV/TV)
To evaluate the effect of the treatment alone or in combination on the Bv/Tv (relative bone trabecular volume) content of the rats, the relative bone trabecular volume of the rats was measured as shown in tables 2 to 6.
Tables 2-6:
the ratio of the relative volumes of the trabeculae (Bv/Tv) can reflect the bone quantity of the trabeculae of different samples, and the increase of the ratio indicates that the anabolism of the bone is greater than the catabolism and the bone quantity is increased, and vice versa, so that the bone metabolism condition can be indirectly reflected.
Sample treatment results show that when N-acetylneuraminic acid and sodium hyaluronate are combined in a certain proportion, a synergistic effect exists, and skeletal development and health can be synergistically promoted, and the relative volume of trabeculae is remarkably increased.
With respect to the components used and the amounts used, experimental example 3 corresponds to the combination of comparative examples 2 and 6, and experimental example 3, comparative example 2, comparative example 6 respectively increased the relative volumes of the bone trabeculae by 0.011%, 0.001%, 0.0074%, and the increase in the relative volumes of the rat bone trabeculae in experimental example 3 (0.011%) was greater than the sum of the respective increases of comparative examples 2 and 6 (0.0084%).
Experiment 4 corresponds to the combination of comparative examples 3 and 5, and experiment 4, comparative example 3, comparative example 5 increased the relative volume of trabecular bone by 0.0111%, 0.0035%, 0.0072%, respectively, and the increase in relative volume of trabecular bone (0.0111%) of experiment 5 was greater than the sum of the self-increases of comparative examples 2 and 4 (0.0107%) relative to the model control.
Similarly, experimental example 6 (corresponding to the combination of comparative example 2 and comparative example 5) can also draw the conclusion of synergy.
Summary of synergistic effects
As shown in the experimental results, when the N-acetylneuraminic acid and the sodium hyaluronate are compounded and used in a certain proportion (for example, when the proportion of the N-acetylneuraminic acid to the sodium hyaluronate is greater than 1:4), experimental examples 2-6 all show a synergistic effect in one or more investigation indexes, and can promote bone health.
Industrial applicability
The use of the nutritional composition provided by the invention for preparing an edible product for improving bone density and bone metabolism can be applied to industrial preparation.
Claims (8)
1. Use of a nutritional composition for the preparation of an edible product for improving bone density and bone metabolism, the composition comprising:
i) N-acetylneuraminic acid substances are used for preparing the medicine,
ii) hyaluronate;
wherein the dosage ratio of the N-acetylneuraminic acid substances to the hyaluronate in the composition is more than 1:4; and, optionally, the composition also includes other nutritional ingredients.
2. The use according to claim 1, wherein the N-acetylneuraminic acid substance is present in one or more of an N-acetylneuraminic acid anhydrate, an N-acetylneuraminic acid hydrate or an N-acetylneuraminic acid salt.
3. The use according to claim 1 or 2, characterized in that the ratio of the amount of N-acetylneuraminic acid substance to the hyaluronate in the composition is 5:1 or less.
4. The use according to claim 1 or 2, characterized in that the N-acetylneuraminic acid substance is selected from one or more of extracts from natural raw materials, chemical syntheses, enzymatic or microbial fermentation broths; the hyaluronate is selected from one or more of animal extract, chemical synthesis or artificial fermentation broth.
5. The use according to claim 1 or 2, wherein the content of the N-acetylneuraminic acid substance is 0.04 mass% or more based on the total mass of the composition; the content of the hyaluronate is 0.01% by mass or more.
6. The use according to claim 1 or 2, characterized in that the ratio of the N-acetylneuraminic acid substance to the hyaluronate is 1:2 to 2:1.
7. Use according to claim 1 or 2, wherein the other nutritional ingredients comprise one or more of proteins, vitamins, monosaccharides, polysaccharides or plant extracts; the composition is a liquid, semi-solid or solid.
8. Use according to claim 1 or 2, characterized in that the edible product comprises a dairy product and in that the dairy product comprises a pediatric dairy product, a maternal, middle aged and elderly dairy product.
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| JPH07316177A (en) * | 1994-03-31 | 1995-12-05 | Snow Brand Milk Prod Co Ltd | New oligosaccharide, production and use thereof |
| JP2004182618A (en) * | 2002-11-29 | 2004-07-02 | Oji Paper Co Ltd | Therapeutic agent for osteoporosis |
| CN102143693A (en) * | 2008-07-02 | 2011-08-03 | N.V.努特里西阿公司 | Nutritional composition for improving muscle function and daily activity |
| CN104781392A (en) * | 2012-11-15 | 2015-07-15 | 国际干细胞公司 | Differentiation of human fibroblast cells |
| CN114403235A (en) * | 2022-01-10 | 2022-04-29 | 成都桥然生物科技有限公司 | Bone-good probiotic formula milk powder for preventing senile osteoporosis |
| CN115644258A (en) * | 2021-12-31 | 2023-01-31 | 君乐宝乳业集团有限公司 | Health milk powder for women and its preparation method |
| CN115736256A (en) * | 2022-12-02 | 2023-03-07 | 黑龙江飞鹤乳业有限公司 | Functional composition for auxiliary protection of bone joint |
-
2023
- 2023-04-11 CN CN202310378093.0A patent/CN116098201B/en active Active
-
2024
- 2024-04-03 WO PCT/CN2024/085972 patent/WO2024212868A1/en unknown
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07316177A (en) * | 1994-03-31 | 1995-12-05 | Snow Brand Milk Prod Co Ltd | New oligosaccharide, production and use thereof |
| JP2004182618A (en) * | 2002-11-29 | 2004-07-02 | Oji Paper Co Ltd | Therapeutic agent for osteoporosis |
| CN102143693A (en) * | 2008-07-02 | 2011-08-03 | N.V.努特里西阿公司 | Nutritional composition for improving muscle function and daily activity |
| CN104781392A (en) * | 2012-11-15 | 2015-07-15 | 国际干细胞公司 | Differentiation of human fibroblast cells |
| CN115644258A (en) * | 2021-12-31 | 2023-01-31 | 君乐宝乳业集团有限公司 | Health milk powder for women and its preparation method |
| CN114403235A (en) * | 2022-01-10 | 2022-04-29 | 成都桥然生物科技有限公司 | Bone-good probiotic formula milk powder for preventing senile osteoporosis |
| CN115736256A (en) * | 2022-12-02 | 2023-03-07 | 黑龙江飞鹤乳业有限公司 | Functional composition for auxiliary protection of bone joint |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2024212868A1 (en) | 2024-10-17 |
| CN116098201B (en) | 2023-06-20 |
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