Anti-aging composition as well as preparation method and application thereof

Abstract

The invention discloses an anti-aging composition as well as a preparation method and application thereof. The anti-aging composition contains the following active raw materials: calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine, L-lysine, vitamin C, cupric citrate, zinc glycinate and ferrous sulfate, and also contains the following auxiliary materials: talcum powder, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and glyceryl behenate. The anti-aging composition is prepared by respectively granulating and mixing. The anti-aging composition can significantly improve the fluidity of the powder and the stability of active substances in the powder, and shows better anti-aging activity in animal experiments.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical preparations, and in particular relates to an anti-aging composition and a preparation method and application thereof. Background Art

[0002] α-Ketoglutarate (AKG) is an organic compound that plays a key role in cell metabolism. It is an important intermediate product of the tricarboxylic acid cycle (TCA cycle) and is involved in energy metabolism and amino acid synthesis. Studies in recent years have shown that AKG has potential application value in anti-aging. Studies have found that AKG can exert anti-aging effects through multiple mechanisms. First, it may affect cell growth and metabolism by regulating the mTOR signaling pathway, which is similar to the anti-aging effect caused by calorie restriction. Secondly, AKG may maintain cell health by promoting autophagy to clean up damaged cellular components. In addition, AKG also has antioxidant effects, which can reduce age-related oxidative stress and protect cells from damage. Experimental data show that AKG can extend the lifespan of animal models and improve their health status. In human studies, middle-aged and elderly people who have long-term supplementation with AKG and vitamin compound preparations have shown a significant reduction in physiological age and improved sleep quality and energy levels. In addition, AKG plays an important regulatory role in protein synthesis, skeletal muscle development and metabolism, calcium stability, etc. AKG can regulate physiological processes such as muscle and bone development, cell metabolism, immune inflammation and stem cell development through complex signaling pathways. These advances are of great value for the application of AKG as an anti-aging supplement in health products.

[0003] Calcium α-ketoglutarate (Ca-AKG) is an important source of α-ketoglutarate anions. α-ketoglutarate anions are intermediates in the Krebs cycle of eukaryotic organisms and are the material basis for AKG to function in vivo. Therefore, Ca-AKG has broad prospects for medical applications.

[0004] In order to realize the application of calcium α-ketoglutarate in medicines, health products, and foods, it is necessary to make it into a safe, effective, and convenient dosage form. Patent document WO2018200736A3 discloses a calcium α-ketoglutarate composition, which is basically composed of a therapeutically effective amount of Ca-AKG and vitamin C, and discloses that the composition can be formulated into tablets, powders, suspensions, slurries, emulsions, capsules, granules, pills, gels, solutions or syrups for oral administration. However, the document does not further disclose the specific formulation prescription and preparation method for the preparation of the Ca-AKG composition.

[0005] Patent 202410297005.9 discloses an anti-aging composition, including: 20-2000 parts of calcium α-ketoglutarate, 20-100 parts of quercetin, 20-2000 parts of trans-resveratrol, 20-100 parts of calendula, and 0.02-1.8 parts of spermidine. The composition targets the 12 major causes of aging and has multi-target synergistic effects, so it contains many natural polyphenol compounds. However, the ingredients contained in this invention are relatively single in orientation, mostly antioxidants, but it does not take into account the need for comprehensive nutritional supplementation to delay aging. Patent 202080052370.3 discloses a composition comprising a therapeutically effective amount of calcium α-ketoglutarate and a controlled release matrix, wherein the controlled release matrix comprises hydroxypropyl methylcellulose. The preparation provided by this invention contains only a single physiologically active ingredient, calcium α-ketoglutarate, and cannot fully meet the needs of comprehensive nutritional supplementation. Patent CN104797248 B discloses a composition and its medical use in neurological and / or neurodegenerative diseases, neurotrauma, depression or chronic fatigue syndrome, wherein the composition comprises d-ketoglutarate or a pharmaceutically acceptable salt thereof (AKG), and one or more enzymes selected from the group consisting of lipase, protease and amylase. Therefore, it is necessary to develop a comprehensive nutritional supplement containing calcium α-ketoglutarate for anti-aging.

[0006] Fish collagen peptides are a type of low molecular weight polypeptide mixture extracted from collagen with multiple active functions. Its structure is relatively loose and easy to be extracted, absorbed and utilized. Fish collagen peptides can be absorbed by the human body and participate in the synthesis of collagen. They are widely distributed in the skin, bones, cornea and other organs of the body and have multiple unique functions, such as support, cushioning and protection. Fish collagen peptides of different molecular weights have certain differences in their efficacy. When the molecular weight is less than 1×10 3 When the content is 1×10 g / mol, it is easier to be absorbed and has excellent moisturizing, anti-oxidative stress, anti-photoaging and other effects. Studies in recent years have shown that oral fish collagen peptides can act on the skin safely and efficiently, exerting antioxidant, inhibiting melanin formation, delaying aging and anti-photoaging effects. Low molecular weight fish collagen peptides can be directly absorbed by the human body without the need for enzyme decomposition, and can be targeted and enriched in the skin after oral administration. Low molecular weight fish collagen peptides increase the exposed area of ​​amino acids, enhance the adsorption capacity of water molecules, stimulate the synthesis of hyaluronic acid (HA), promote the expression of aquaporins, increase skin hydration, and enhance moisturizing properties. In anabolism, especially those with a molecular weight below 1×10 3 The fish collagen peptide with a content of 100 g / mol can efficiently remove free radicals and has excellent antioxidant capacity. Studies have also found that the hydroxyproline in fish collagen peptide can promote collagen synthesis and inhibit collagen degradation and melanin formation.

[0007] Amino acids also have many benefits for the skin. Amino acids play an important role in the repair of skin damage. Collagen is one of the main components required for skin repair, and a large amount of amino acids are needed to synthesize collagen. Supplementing amino acids can promote the formation of new collagen, thereby accelerating skin repair. Amino acids can regulate the pH value of the skin surface and maintain a slightly acidic environment. This helps to maintain the normal physiological function of the skin and fight against the occurrence of skin diseases or infections. Some amino acids have strong antioxidant effects, such as glutathione and arginine. They can help resist the invasion of free radicals, protect the skin from damage, and delay the aging process of the skin. Some amino acids have good moisturizing effects and can absorb moisture and improve the skin's moisturizing ability. Amino acids such as glycine and serine are considered to have good natural moisturizing effects and can keep the skin hydrated. Some amino acids can stimulate the production of growth factors, promote the growth and differentiation of skin cells, and thus help keep the skin healthy. Arginine, leucine, etc. are amino acids that have the effect of stimulating growth factors.

[0008] Vitamin C, also known as ascorbic acid, can participate in the body's metabolism and is used to prevent and treat scurvy. It can increase the body's resistance to disease transmission, improve the body's own immune function, and has a certain anti-stress ability. Vitamin C is an important nutrient with a certain antioxidant effect. It can remove free radicals in the body and can delay aging.

[0009] In recent years, scientific research has shown that aging is closely related to trace elements. For example, iron is an essential trace element for the human body and an indispensable key nutrient for the normal operation of the blood system, digestive system and immune system. Various types of proteases are very important catalysts with multiple functions such as digestion, absorption, immunity and synthesis, and the production of many enzymes requires the participation of iron. For example, carotene needs to be converted into vitamin A after entering the human body by an oxygenase, and this oxygenase contains iron. Therefore, iron deficiency can easily lead to a series of trace element deficiency symptoms, affecting life and health. In addition, once iron is deficient, muscle tissue is prone to hypoxia, which in turn causes poor blood oxygen circulation, shortened cell life, nerve conduction disorders, etc. Therefore, people with iron deficiency are at greater risk of cardiovascular and cerebrovascular accidents such as myocardial infarction and cerebral infarction. Related studies have shown that the damage to the nervous system caused by iron deficiency is not only serious, but also irreversible. Zinc is a trace element essential to all life, and its content in the human body is second only to iron. Zinc in the human body is Zn 2＋ Ions are present as central ions in many enzymes or metalloproteins. It is now known that there are about a variety of zinc enzymes and those that require Zn in the human body. 2＋Ions activate enzymes. These enzymes are widely involved in a series of metabolic processes in the human body, including the synthesis and decomposition of sugars, fats, proteins and nucleic acids. Among them, DNA and RNA polymerases are enzymes that synthesize nucleic acids and proteins. When base pairing errors occur, they have the function of promoting repair, which is particularly important for the elderly. Zinc is closely related to growth and development. Zinc deficiency can cause growth retardation, decreased sexual function and fertility. Zinc affects taste and appetite. Zinc deficiency can cause decreased appetite in the elderly. Zinc is needed to maintain vision. Zinc deficiency can affect vision and cause night blindness. Zinc can improve immune function. It is a substance necessary to maintain the body's normal immune function and defense function. Zinc can bind to thiols and block the strong catalytic free radical reaction caused by the combination of thiols and iron. Zinc can also inhibit lipid peroxidation, stabilize the structure and function of cells, and make cells have a strong resistance to ions or free radicals. Therefore, zinc can delay aging. Copper is the third most abundant essential trace element in the human body. Copper-containing enzymes include tyrosinase, monoamine oxidase, superoxidase, superoxide dismutase, and ceruloplasmin. 2＋ It activates the formation of hemoglobin, promotes the absorption and utilization of iron, and is involved in the transfer of electrons, the synthesis of elastin, the metabolism of connective tissue, the metabolism of purine phospholipids and the formation of nerve tissue. Summary of the invention

[0010] The primary purpose of the present invention is to provide a comprehensive nutritional supplement containing Ca-AKG for anti-aging.

[0011] To achieve the above object, the present invention adopts the following technical solution:

[0012] An anti-aging composition comprising the following components by weight:

[0013] Calcium ketoglutarate 8%~20%, fish collagen peptide 30%~45%, glycine 0.1%~1.0%, L-proline 0.1%~1.0%, L-alanine 0.1%~1.0%, L-lysine 0.1%~1.0%, coated vitamin C 0.5%~3.0%, copper citrate 0.05%~1.00%, zinc glycinate 0.01%~1.00%, ferrous sulfate 0.01%~1.00%, talc 0.1%~1.0%, microcrystalline cellulose 30%~45%, low-substituted hydroxypropyl cellulose 2%~15%, and glyceryl behenate 0.01%~1.00%.

[0014] Preferably, the anti-aging composition comprises the following components in mass content:

[0015] Calcium ketoglutarate 10%~18%, fish collagen peptide 32%~43%, glycine 0.2%~0.8%, L-proline 0.2%~0.8%, L-alanine 0.1%~0.8%, L-lysine 0.2%~0.8%, coated vitamin C 0.5%~2.0%, copper citrate 0.08%~1.00%, zinc glycinate 0.01%~0.08%, ferrous sulfate 0.04%~1.00%, talc 0.2%~0.8%, microcrystalline cellulose 31.96%~38.92%, low-substituted hydroxypropyl cellulose 5%~11%, and glyceryl behenate 0.01%~0.5%.

[0016] Preferably, the anti-aging composition comprises the following components in mass content:

[0017] Calcium ketoglutarate 12.60%, fish collagen peptide 36.68%, glycine 0.55%, L-proline 0.42%, L-alanine 0.22%, L-lysine 0.54%, coated vitamin C 1.08%, copper citrate 0.13%, zinc glycinate 0.05%, ferrous sulfate 0.09%, talc 0.52%, microcrystalline cellulose 39.17%, low-substituted hydroxypropyl cellulose 7.85%, and behenic acid glyceryl 0.1%.

[0018] The second object of the present invention is to provide a method for preparing the anti-aging composition, comprising the following steps:

[0019] (1) preparing wet granules from powders of calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine, L-lysine, microcrystalline cellulose and low-substituted hydroxypropyl cellulose, and then drying to obtain first granules;

[0020] (2) mixing powders of copper citrate, zinc glycinate, ferrous sulfate and glyceryl behenate to prepare second particles;

[0021] (3) Mix the first granules and the second granules, add coated vitamins and talcum powder, and mix well to obtain the product.

[0022] Preferably, step (1) comprises the following steps:

[0023] (1-1) After powders of calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine and L-lysine are uniformly mixed, powders of microcrystalline cellulose and low-substituted hydroxypropyl cellulose are added and uniformly mixed to obtain a mixed powder;

[0024] (1-2) adding a binder to the mixed powder to prepare a soft material;

[0025] (1-3) extruding the soft material through a sieve to obtain wet granules;

[0026] (1-4) The wet granules are dried and sieved to obtain the product.

[0027] Preferably, step (2) comprises the following steps:

[0028] (2-1) Mixing powders of copper citrate, zinc glycinate and ferrous sulfate, and adding glyceryl behenate to obtain a second mixture;

[0029] (2-2) The second mixture is heated and stirred in a water bath, then taken out of the water bath and continued to be stirred until the mixture reaches room temperature, and then sieved to obtain the mixture.

[0030] Preferably, the binder in step (1-2) is water.

[0031] The state of the soft material is that it can be formed into a ball when held by hand and will fall apart when pressed lightly.

[0032] Preferably, the sieve described in step (1-3) is 18 mesh.

[0033] Preferably, the drying conditions in step (1-4) are: drying at 45°C to 55°C for 1.5 h to 2 h.

[0034] Preferably, the screening in step (1-4) is through a 18-mesh sieve.

[0035] Preferably, the temperature of the water bath in step (2-2) is 60° C. to 70° C., and the stirring time in the water bath is 10 to 15 minutes.

[0036] Preferably, the powder has a particle size that can pass through an 80-mesh sieve.

[0037] The beneficial technical effects of the present invention are mainly reflected in the following aspects:

[0038] The present invention provides an anti-aging comprehensive nutritional supplement, which contains, in addition to Ca-AKG, fish collagen peptides, glycine, L-proline, L-alanine, and L-lysine for supplementing key amino acids and having anti-aging effects; vitamin C, a strong antioxidant; and copper citrate, zinc glycinate, and ferrous sulfate for supplementing trace elements. According to the biological activities of the above substances, they can theoretically synergistically fight aging from different angles.

[0039] However, simply mixing the above materials will bring some problems.

[0040] First, after the above materials are simply mixed, the stability of the powder is poor. For example, the presence of metal ions can catalyze the oxidation and deterioration of vitamin C.

[0041] Secondly, after simply mixing the above materials, the fluidity of the powder is not improved. This is mainly because in comprehensive supplements, Ca-AKG and fish collagen peptides account for a large proportion, and the powder fluidity of these two substances is not good. In addition, the fluidity of several amino acids and trace elements is not good. The problem caused by poor powder fluidity is that it is difficult to further process the materials into common dosage forms such as tablets and capsules.

[0042] Again, after simply mixing the above materials, the powder taste is not added. This problem is mainly caused by metal salts such as copper citrate, zinc glycinate, and ferrous sulfate.

[0043] In view of the above problems, the present invention also provides a preparation processing technology, and some necessary auxiliary materials need to be added for granulation. The auxiliary materials include microcrystalline cellulose, low-substituted hydroxypropyl cellulose, talc, and glyceryl behenate.

[0044] The present invention provides a comprehensive nutritional supplement for anti-aging. There are clear research conclusions on the anti-aging effect of Ca-AKG, but the human aging process is composed of multiple links. It is obviously not enough to simply use Ca-AKG as an anti-aging supplement. The comprehensive nutritional supplement for anti-aging provided by the present invention, in addition to Ca-AKG, also contains fish collagen peptides, glycine, L-proline, L-alanine, and L-lysine for supplementing key amino acids and having anti-aging effects; it also contains vitamin C, a strong antioxidant; it also contains copper citrate, zinc glycinate, and ferrous sulfate for supplementing trace elements. The added ingredients have different roles in the anti-aging process and can play a synergistic role.

[0045] The present invention improves the fluidity of the powder of the comprehensive nutritional supplement. The powder obtained by simply mixing the nutrients contained in the comprehensive nutritional supplement has poor fluidity. By adding necessary auxiliary materials and developing a targeted granulation process, the fluidity of the powder is greatly improved, thereby facilitating further processing and use.

[0046] The present invention improves the stability of the comprehensive nutritional supplement powder. This is mainly achieved by granulating different types of nutrients separately. Through the preparation process, fish collagen peptide, glycine, L-proline, L-alanine, and L-lysine are first granulated by a wet granulation process, and then copper citrate, zinc glycinate, and ferrous sulfate are granulated by a hot melt coating method, and then coated vitamin C directly purchased is added, and several types of nutrients are reasonably physically isolated, which greatly improves stability.

[0047] The present invention improves the mouthfeel of the comprehensive nutritional supplement powder. Unprocessed metal salts such as copper citrate and ferrous sulfate will bring a bad taste. After hot-melt granulation of several metal salts with behenic acid glyceryl, the metal salts are effectively encapsulated and bring a certain sustained-release effect, so no easily perceptible metallic taste is produced after the mouth is ingested. This is because after heating and melting, behenic acid glyceryl can form a film on the surface of the metal salt, and the property of solidification after cooling limits the rapid release of the metal salt in the oral cavity, thereby achieving a taste-masking effect. DETAILED DESCRIPTION

[0048] The following examples further describe the preparation process and beneficial effects of the present invention. The examples are only for illustrative purposes and do not limit the scope of the present invention.

[0049] Example 1

[0050] (1) Prepare the components according to the following mass proportions:

[0051] Calcium ketoglutarate 18%, fish collagen peptide 32%, glycine 0.2%, L-proline 0.2%, L-alanine 0.1%, L-lysine 0.2%, microcrystalline cellulose 38.92%, low-substituted hydroxypropyl cellulose 5%, coated vitamin C 2.0%, copper citrate 1.00%, zinc glycinate 0.08%, ferrous sulfate 1.00%, behenic acid glyceryl 0.5%, talc 0.8%.

[0052] (2) Except for vitamin C (coating), all materials are mechanically crushed and passed through an 80-mesh sieve.

[0053] (3) After uniformly mixing the prescribed amount of calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine and L-lysine, add microcrystalline cellulose and low-substituted hydroxypropyl cellulose and mix them uniformly, add appropriate amount of water to make a soft material, so that the soft material reaches the state of "forming a ball when held in the hand and falling apart when pressed lightly", and the soft material is passed through an 18-mesh sieve. The obtained wet granules are dried in a 45°C forced air drying oven for 2 h, and then passed through an 18-mesh sieve to obtain the first type of granules.

[0054] (4) Mix the prescribed amount of copper citrate, zinc glycinate and ferrous sulfate, add behenic acid glyceryl, heat in a 60°C water bath with stirring for 15 minutes, remove from the water bath and continue stirring to room temperature, and pass through an 18-mesh sieve to obtain the second type of particles.

[0055] (5) Mix the first and second type granules, add the prescribed amount of coated vitamin C and talcum powder, and mix well to obtain the product.

[0056] Example 2

[0057] (1) Prepare the components according to the following mass proportions:

[0058] Calcium ketoglutarate 10%, fish collagen peptide 43%, glycine 0.8%, L-proline 0.8%, L-alanine 0.8%, L-lysine 0.8%, microcrystalline cellulose 31.96%, low-substituted hydroxypropyl cellulose 11%, vitamin C (coated) 0.5%, copper citrate 0.08%, zinc glycinate 0.01%, ferrous sulfate 0.04%, glyceryl behenate 0.01%, talc 0.2%.

[0059] (2) Except for vitamin C (coating), all materials are mechanically crushed and passed through an 80-mesh sieve.

[0060] (3) After uniformly mixing the prescribed amount of calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine and L-lysine, add microcrystalline cellulose and low-substituted hydroxypropyl cellulose and mix them uniformly, add appropriate amount of water to make a soft material, so that the soft material reaches the state of "holding into a ball by hand and falling apart when lightly pressed". The soft material is passed through an 18-mesh sieve, and the obtained wet granules are dried in a 55°C forced air drying oven for 1.5 hours, and then passed through an 18-mesh sieve to obtain the first type of granules.

[0061] (4) Mix the prescribed amount of copper citrate, zinc glycinate and ferrous sulfate, add behenic acid glyceryl, heat in a 70°C water bath with stirring for 10 minutes, remove from the water bath and continue stirring to room temperature, and pass through an 18-mesh sieve to obtain the second type of particles.

[0062] (5) Mix the first and second type granules, add the prescribed amount of coated vitamin C and talcum powder, and mix well to obtain the product.

[0063] Example 3

[0064] (1) Prepare the components according to the following mass proportions:

[0065] Calcium ketoglutarate 10%, fish collagen peptide 32%, glycine 0.8%, L-proline 0.8%, L-alanine 0.8%, L-lysine 0.8%, microcrystalline cellulose 42.96%, low-substituted hydroxypropyl cellulose 11%, vitamin C (coating) 0.5%, copper citrate 0.08%, zinc glycinate 0.01%, ferrous sulfate 0.04%, glyceryl behenate 0.01%, talc 0.2%.

[0066] (2) Except for vitamin C (coating), all materials are mechanically crushed and passed through an 80-mesh sieve.

[0067] (3) After uniformly mixing the prescribed amount of calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine and L-lysine, add microcrystalline cellulose and low-substituted hydroxypropyl cellulose and mix them uniformly, add appropriate amount of water to make a soft material, so that the soft material reaches the state of "forming a ball when held in the hand and falling apart when pressed lightly", and the soft material is passed through an 18-mesh sieve. The obtained wet granules are dried in a 45°C forced air drying oven for 2 h, and then passed through an 18-mesh sieve to obtain the first type of granules.

[0068] (4) Mix the prescribed amount of copper citrate, zinc glycinate and ferrous sulfate, add behenic acid glyceryl, heat in a 70°C water bath with stirring for 10 minutes, remove from the water bath and continue stirring to room temperature, and pass through an 18-mesh sieve to obtain the second type of particles.

[0069] (5) Mix the first and second type granules, add the prescribed amount of coated vitamin C and talcum powder, and mix well to obtain the product.

[0070] Example 4

[0071] (1) Prepare the components according to the following mass proportions:

[0072] Calcium ketoglutarate 12.60%, fish collagen peptide 36.68%, glycine 0.55%, L-proline 0.42%, L-alanine 0.22%, L-lysine 0.54%, microcrystalline cellulose 39.17%, low-substituted hydroxypropyl cellulose 7.85%, vitamin C (coated) 1.08%, copper citrate 0.13%, zinc glycinate 0.05%, ferrous sulfate 0.09%, behenic acid glyceryl 0.1%, talc 0.52%.

[0073] (2) Except for vitamin C (coating), all materials are mechanically crushed and passed through an 80-mesh sieve.

[0074] (3) After uniformly mixing the prescribed amount of calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine and L-lysine, add microcrystalline cellulose and low-substituted hydroxypropyl cellulose and mix them uniformly, add appropriate amount of water to make a soft material, so that the soft material reaches the state of "forming a ball when held in the hand and falling apart when pressed lightly", and the soft material is passed through an 18-mesh sieve. The obtained wet granules are dried in a 45°C forced air drying oven for 2 h, and then passed through an 18-mesh sieve to obtain the first type of granules.

[0075] (4) Mix the prescribed amount of copper citrate, zinc glycinate and ferrous sulfate, add behenic acid glyceryl, heat in a 70°C water bath with stirring for 10 minutes, remove from the water bath and continue stirring to room temperature, and pass through an 18-mesh sieve to obtain the second type of particles.

[0076] (5) Mix the first and second type granules, add the prescribed amount of coated vitamin C and talcum powder, and mix well to obtain the product.

[0077] Comparative Example 1

[0078] (1) Prepare the components according to the following mass proportions:

[0079] Calcium ketoglutarate 20%, fish collagen peptide 63.84%, glycine 1.6%, L-proline 1.6%, L-alanine 1.6%, L-lysine 1.6%, vitamin C (coated) 4.0%, copper citrate 2.0%, zinc glycinate 0.16%, ferrous sulfate 2.0%, talc 1.6%.

[0080] (2) Except for vitamin C (coating), all materials are mechanically crushed and passed through an 80-mesh sieve.

[0081] (3) Mix the prescribed amount of calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine, L-lysine, copper citrate, zinc glycinate, and ferrous sulfate, and then add the prescribed amount of coated vitamin C and talcum powder. Mix well to obtain the product.

[0082] Comparative Example 2

[0083] (1) Prepare the components according to the following mass proportions:

[0084] Calcium ketoglutarate 12.60%, fish collagen peptide 36.68%, glycine 0.55%, L-proline 0.42%, L-alanine 0.22%, L-lysine 0.54%, microcrystalline cellulose 39.27%, low-substituted hydroxypropyl cellulose 7.85%, vitamin C (coated) 1.08%, copper citrate 0.13%, zinc glycinate 0.05%, ferrous sulfate 0.09%, behenic acid glyceryl 0.1%, talc 0.52%.

[0085] (2) Except for vitamin C (coating), all materials are mechanically crushed and passed through an 80-mesh sieve.

[0086] (3) Mix the prescribed amount of calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine, L-lysine, copper citrate, zinc glycinate, and ferrous sulfate, and then add the prescribed amount of coated vitamin C, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, talc, glyceryl behenate, and talc. Mix well to obtain the product.

[0087] Test 1 Preliminary study on powder science

[0088] The angle of repose is the angle between the free slope of the powder accumulation layer and the horizontal plane. The smaller the angle of repose, the better the fluidity. It is generally believed that the material has good fluidity when the angle of repose is ≤30°.

[0089] Place a plastic funnel with a bottom diameter of 7 mm on an iron stand, seal the bottom of the funnel, and place a glass dish on the laboratory table about 10 cm away from the bottom of the funnel, and ensure that the center of the glass dish is aligned with the center of the funnel mouth. Pour 50 g of powder into the funnel, open the bottom of the funnel, wait for the powder to flow out, and wait for 2 minutes until the powder pile stabilizes. Use paper as a background, mark the distance h (cm, minus the thickness of the bottom of the glass dish 0.1 cm) from the vertex of the powder cone to the horizontal plane on the paper, and measure the radius r (cm) of the bottom of the powder cone.

[0090] Measure 3 groups separately and calculate the angle of repose θ.

[0091] That is: tan θ = (h − 0.1) / r

[0092] Among them, θ is the angle of repose, h is the distance from the cone vertex to the horizontal plane, and r is the radius of the cone base.

[0093] The outflow rate refers to the amount of powder that flows out of the small hole in the container per unit time. The faster the outflow rate, the better the fluidity of the powder. Use the device for measuring the angle of repose as described above. Put 50 g of powder into a beaker. Weigh the total mass of the powder and beaker (m1). While starting the stopwatch, pour the powder into the funnel. If necessary, gently stir with a glass rod to aid leakage. Stop the timer when the leakage is completed and record the required time t. Weigh the mass of the empty beaker after the powder is poured out (m2). Calculate the outflow rate of the powder.

[0094] Outflow velocity = (m1-m2) / t

[0095] m1 is the total mass of the powder and beaker, m2 is the total mass of the empty beaker, and t is the time required for all the powder to flow out.

[0096] The angle of repose and outflow velocity of each powder are shown in Table 1.

[0097] Table 1 Angle of repose and outflow velocity of each powder

[0098] Powder Origin Angle of repose (°) Outflow rate (g / s) Example 1 26 2.83 Example 2 24 2.91 Example 3 26 2.81 Example 4 21 3.14 Comparative Example 1 37 0.99 Comparative Example 2 34 0.93

[0099] According to the principle of powder science, the larger the angle of repose of the powder, the worse the fluidity; the lower the outflow rate of the powder, the worse the fluidity of the powder. As can be seen from the results, the powder fluidity of Comparative Example 1, which did not add excipients and was not processed by the formulation step, was very poor; the powder fluidity of Comparative Example 2, which added excipients but was not processed by the formulation step, was not significantly improved. In comparison, Examples 1 to 4 showed a lower angle of repose and a faster outflow rate, showing that the formulation technology provided by the present invention can effectively improve the powder properties of comprehensive nutritional supplements.

[0100] Test Example 2 Preliminary study on high temperature stability

[0101] The six powders were placed in a comprehensive drug stability test chamber, the temperature was set at 50°C, away from light, kept dry, and left for a long time. Samples were taken at different time points to measure the changes in the content of the less stable vitamin C and fish collagen peptides, and the percentages of the two substances were calculated.

[0102] The experimental results are shown in Tables 2 and 3.

[0103] Table 2 Vitamin C content percentage (relative to the content in month 0)

[0104] Powder Origin 1 month 3 months 6 months Example 1 99.3% 98.3% 96.2% Example 2 98.8% 97.5% 95.2% Example 3 99.1% 98.2% 96.0% Example 4 99.8% 98.6% 96.7% Comparative Example 1 73.2% 41.0% 18.1% Comparative Example 2 77.6% 48.3% 24.8%

[0105] Table 3 Percentage of fish collagen content (relative to the content in 0 month)

[0106] Powder Origin 1 month 3 months 6 months Example 1 99.7% 99.7% 99.3% Example 2 99.7% 99.3% 99.0% Example 3 99.8% 99.2% 99.2% Example 4 99.8% 99.6% 99.5% Comparative Example 1 97.3% 90.2% 82.6% Comparative Example 2 97.6% 92.1% 85.1%

[0107] According to the preliminary study results of high temperature stability, Experimental Examples 1 to 4 prepared by the preparation method provided by the present invention can better maintain the stability of vitamin C and fish collagen. The vitamin C and fish collagen content in Comparative Example 1 without adding auxiliary materials and without preparation steps, and Comparative Example 2 with auxiliary materials but without preparation steps decreased significantly.

[0108] The methods for determining vitamin C and fish collagen are as follows.

[0109] (1) Vitamin C content determination method:

[0110] Preparation of reference solution: Weigh an appropriate amount of vitamin C reference solution, dissolve it in mobile phase and quantitatively dilute it into a solution containing 50 μg per 1 mL, and determine it in the same way.

[0111] Preparation of the test solution: Take 10 g of powder (Experimental Examples 1-4, Comparative Examples 1-2), grind it into powder, accurately weigh an appropriate amount of fine powder (equivalent to approximately 2.5 mg of vitamin C), place it in a 50 mL volumetric flask, add an appropriate amount of mobile phase, sonicate to dissolve the vitamin C, dilute to the scale with the mobile phase, shake well, filter, and use as the test solution.

[0112] Chromatographic conditions: chromatographic column: Sunniest C18 (5 μm, 4.6 mm id × 250 mm); mobile phase: 10 mM sodium acetate buffer (acetic acid adjusted to pH 6.5); detection wavelength: 270 nm; flow rate: 1.0 mL / min; column temperature: 30°C; injection volume: 20 μL.

[0113] Determination method: Accurately measure 20 μL of each of the above two solutions, inject them into liquid chromatograph, record the chromatogram, and calculate the content by peak area according to the external standard method.

[0114] (2) Determination method of fish collagen content:

[0115] According to the Chinese Pharmacopoeia 2020 edition Part III-General Part III 0731 Protein Determination Method, this study adopted the "Third Method Biuret Method". This method is based on the reaction of two or more peptide bonds in a protein molecule with Cu in an alkaline solution. 2+ A purple-red complex is formed, and within a certain range, its color depth is proportional to the protein concentration. The protein reference solution is used as a standard curve, and the protein content in the test sample is determined by colorimetry. Although this method contains four amino acids, according to the principle of the method, only "containing more than two peptide bonds in alkaline solution with Cu 2+ The only thing in the powder that contains more than two peptide bonds is fish collagen peptide, so in principle it can be used for determination. In addition, although the sensitivity of the biuret method for determining protein content is low (the determination range is usually 1 to 10 mg), since the powder contains a large amount of fish collagen peptide, it does not pose a difficulty in determination.

[0116] Biuret test solution: Take 1.5 g of copper sulfate, 6.0 g of potassium sodium tartrate and 5.0 g of potassium iodide, add 500 mL of water to dissolve, add 300 mL of 10% sodium hydroxide solution while stirring, dilute with water to 1000 mL, mix well, and you have the product.

[0117] Reference solution: Accurately weigh fish collagen peptide, dissolve in water and prepare a solution containing 10 mg per 1 mL (10 mg / mL), and store at 4°C.

[0118] Test solution: accurately weigh 100 mg of the prepared powder, place it in a vial, dissolve it with pure water by ultrasonication, transfer it to a 10 mL volumetric flask, and make up to volume with pure water. Then transfer it to a centrifuge tube and centrifuge it at 5000 r / min for 20 min, and take the supernatant. Store it at 4°C.

[0119] Accurately measure 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0 mL of the reference solution, place them in stoppered test tubes, add water to 1.0 mL each, then add 4.0 mL of biuret test solution, mix them immediately, place them at room temperature for 30 min, and measure the absorbance at a wavelength of 540 nm according to the UV-Vis spectrophotometry (General Rule 0401); at the same time, use tube 0 as a blank. Calculate the linear regression equation based on the concentration of the reference solution and its corresponding absorbance. Take 1 mL of each test sample, use tube 0 as a blank, and operate in the same way to determine the protein concentration.

[0120] Test Example 3 Morris water maze test

[0121] Morris water maze is an experimental method designed by British psychologist Morris in the early 1980s (1981) and applied to the study of brain learning and memory mechanisms. It is widely used in AD research. Morris water maze is not only used to study the functional evaluation of brain regions related to spatial learning and memory, but is also widely used in learning and memory, Alzheimer's disease, and hippocampus / extrahippocampus research. Morris water maze experiment has important directional significance in evaluating the anti-aging effect of drugs. See: (1) Anti-aging effect of Lycium barbarum polysaccharide crude extract and its relationship with the signal transduction system Ca 2+ -CaM correlation study. Zhou Xuan. Xinjiang Agricultural University, Master's degree thesis; (2) Experimental study on the anti-aging effect of Angelica polysaccharide. Xu Lu, et al. Laser Journal, 2008(04), 89-90.

[0122] Experimental mouse preparation: 40 male C57BL / 6J mice were selected and randomly divided into 10 treatment groups, as shown in Table 4. In all the above treatment groups, the mice were gavaged with 200 mg / kg of nutrients added to the conventional feed, once a day for 2 months.

[0123] Table 4 The water maze experimental settings and groups are as follows.

[0124] Group Name Recipe Design Normal group Fed conventional feed without any other nutrients added Calcium Ketoglutarate Group Add calcium ketoglutarate to conventional feed Fish collagen peptide group Add fish collagen peptides to conventional feed Mixed amino acid group Mixed amino acids are added to conventional feed, wherein the mixed amino acids are obtained by mixing glycine, L-proline, L-alanine, and L-lysine in equal proportions. Vitamin C Group Add coated vitamin C to regular feed. Mixed trace elements set Mixed trace elements are added to conventional feed, wherein the mixed trace elements are obtained by mixing copper citrate, zinc glycinate, ferrous sulfate in equal proportions. Comprehensive Nutritional Formula Group 1 The powder of Example 1 was added on the basis of feeding conventional feed. Comprehensive Nutritional Formula Group 2 Add the powder of Example 2 to the conventional feed Comprehensive Nutritional Formula Group 3 Add the powder of Example 3 to the conventional feed Comprehensive Nutritional Formula Group 4 Add the powder of Example 4 to the conventional feed

[0125] The Morris water maze system has a diameter of 90 cm and a height of 45 cm. The inner wall is painted black. The maze is filled with tap water and the water temperature is maintained at 23°C. The escape platform is 6 cm in diameter and 24 cm in height. It is located in the center of the fourth quadrant of the maze and is 1 cm below the water surface. A camera is installed directly above the water maze and connected to the equipment analysis system for collecting images and data information. The water maze is divided into four quadrants: Q1, Q2, Q3, and Q4, of which Q3 is the target quadrant, including the escape platform Q5. The experiment is divided into two phases: training phase and testing phase. In the training phase, mice are randomly placed in water in four different quadrants, and the software records the time from entering the water to climbing onto the platform, which is called the escape latency. Each mouse undergoes 4 training sessions a day (entering the water from different quadrants), each recording for 1 minute, for 5 consecutive days. If the mouse still fails to find the platform within 1 minute, it can be manually guided to find the platform and rest for 1 minute. In the test phase, all mice were placed in water from a fixed quadrant (except the target quadrant), and the software recorded for 1 minute and observed their process of finding a safe platform. The escape latency (s) was the terminal observation index. The results are shown in Table 5.

[0126] Table 5. Latency to reach the platform

[0127] Group Name Escape latency (seconds) Normal group 43 ± 5 Calcium Ketoglutarate Group 28 ± 4 Fish collagen peptide group 34 ± 5 Mixed amino acid group 41 ± 4 Vitamin C Group 38 ± 4 Mixed trace elements set 40 ± 3 Comprehensive Nutritional Formula Group 1 18 ± 3 Comprehensive Nutritional Formula Group 2 16 ± 3 Comprehensive Nutritional Formula Group 3 15 ± 3 Comprehensive Nutritional Formula Group 4 15 ± 2

[0128] As can be seen from Table 5, compared with the calcium ketoglutarate group, fish collagen peptide group, mixed amino acid group, vitamin C group, and mixed trace element group, each comprehensive nutritional formula group can significantly reduce the escape latency, indicating that the comprehensive nutritional formula group has a good memory enhancement effect. It can be seen that the anti-aging powders described in Examples 1 to 4 can improve the memory ability of mice.

Claims

1. An anti-aging composition, characterized in that: The composition includes the following mass contents: Calcium ketoglutarate 8%~20%, fish collagen peptide 30%~45%, glycine 0.1%~1.0%, L-proline 0.1%~1.0%, L-alanine 0.1%~1.0%, L-lysine 0.1%~1.0%, coated vitamin C 0.5%~3.0%, copper citrate 0.05%~1.00%, zinc glycinate 0.01%~1.00%, ferrous sulfate 0.01%~1.00%, talc 0.1%~1.0%, microcrystalline cellulose 30%~45%, low-substituted hydroxypropyl cellulose 2%~15%, and glyceryl behenate 0.01%~1.00%.

2. The anti-aging composition according to claim 1, characterized in that The composition includes the following mass contents: Calcium ketoglutarate 10%~18%, fish collagen peptide 32%~43%, glycine 0.2%~0.8%, L-proline 0.2%~0.8%, L-alanine 0.1%~0.8%, L-lysine 0.2%~0.8%, coated vitamin C 0.5%~2.0%, copper citrate 0.08%~1.00%, zinc glycinate 0.01%~0.08%, ferrous sulfate 0.04%~1.00%, talc 0.2%~0.8%, microcrystalline cellulose 31.96%~38.92%, low-substituted hydroxypropyl cellulose 5%~11%, and glyceryl behenate 0.01%~0.5%.

3. The anti-aging composition according to claim 1, characterized in that The composition includes the following mass contents: Calcium ketoglutarate 12.60%, fish collagen peptide 36.68%, glycine 0.55%, L-proline 0.42%, L-alanine 0.22%, L-lysine 0.54%, coated vitamin C 1.08%, copper citrate 0.13%, zinc glycinate 0.05%, ferrous sulfate 0.09%, talc 0.52%, microcrystalline cellulose 39.17%, low-substituted hydroxypropyl cellulose 7.85%, and behenic acid glyceryl 0.1%.

4. The method for preparing the anti-aging composition according to any one of claims 1 to 3, characterized in that: The steps include: (1) preparing wet granules from powders of calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine, L-lysine, microcrystalline cellulose and low-substituted hydroxypropyl cellulose, and then drying to obtain first granules; (2) mixing powders of copper citrate, zinc glycinate, ferrous sulfate and glyceryl behenate to prepare second particles; (3) Mix the first granules and the second granules, add coated vitamins and talcum powder, and mix well to obtain the product.

5. The preparation method according to claim 4, characterized in that: Step (1) includes the following steps: (1-1) After powders of calcium ketoglutarate, fish collagen peptide, glycine, L-proline, L-alanine and L-lysine are uniformly mixed, powders of microcrystalline cellulose and low-substituted hydroxypropyl cellulose are added and uniformly mixed to obtain a mixed powder; (1-2) adding a binder to the mixed powder to prepare a soft material; (1-3) extruding the soft material through a sieve to obtain wet granules; (1-4) The wet granules are dried and sieved to obtain the product.

6. The preparation method according to claim 5, characterized in that: The binder in step (1-2) is water.

7. The preparation method according to claim 5, characterized in that The drying conditions described in step (1-4) are: drying at 45°C~55°C for 1.5 h~2 h.

8. The preparation method according to claim 4, characterized in that: Step (2) includes the following steps: (2-1) Mixing powders of copper citrate, zinc glycinate and ferrous sulfate, and adding glyceryl behenate to obtain a second mixture; (2-2) The second mixture is heated and stirred in a water bath, then taken out of the water bath and continued to be stirred until the mixture reaches room temperature, and then sieved to obtain the mixture.

9. The preparation method according to claim 5, characterized in that: The temperature of the water bath in step (2-2) is 60°C to 70°C, and the stirring time in the water bath is 10 to 15 minutes.

10. The preparation method according to claim 4, characterized in that: The powder has a particle size that can pass through an 80-mesh sieve.