Oral composition containing vitamin C nicotinamide eutectic and application thereof

Abstract

The invention discloses an oral composition containing a vitamin C nicotinamide eutectic crystal. The composition comprises the following components in parts by weight: 15-35 parts of vitamin C-nicotinamide eutectic, active polysaccharide, phosphatidylserine, a natural calming component, astaxanthin, prebiotic oligosaccharide, lactoferrin, vitamin D3, an amino acid derivative and the like. The vitamin C and the nicotinamide exist in a eutectic form, so that the stability of the vitamin C and the bioavailability of the nicotinamide are improved, and the vitamin C and the nicotinamide synergistically exert an anti-oxidation effect. Meanwhile, various nutritional ingredients in the composition have a synergistic effect, so that the composition has comprehensive health-care effects in the aspects of supplementing nutrition, regulating immunity, improving sleep and the like.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical cocrystals and nutritional health foods, and particularly relates to an oral composition containing vitamin C nicotinamide cocrystal and an application thereof. Background Art

[0002] Nicotinamide is a water-soluble vitamin and a member of the B vitamin complex. It is naturally found primarily in cereal husks, yeast, peanuts, meat, animal organs, milk, and leafy greens. It can be synthesized in the human body from tryptophan, but inefficiently. Its antioxidant properties can slow or block melanin formation, or act on melanin-producing cells, making it a common ingredient in whitening cosmetics. Nicotinamide is a component of coenzyme I and coenzyme II, acting as a coenzyme for many dehydrogenases. Its deficiency can impair normal cellular respiration and metabolism, leading to pellagra. Oral nicotinamide is commonly used to prevent and treat pellagra, stomatitis, and glossitis.

[0003] In addition, nicotinamide adenine dinucleotide (NAD + ) is the basis of cellular energy metabolism, directly or indirectly affecting key cellular functions such as cellular metabolic pathways, DNA repair, chromatin remodeling, and cellular immunity, and is also a common substrate for multiple enzymes. + Level imbalance is closely related to cardiovascular disease, obesity, neurodegeneration, aging and other pathological processes. Therefore, stable NAD + Nicotinamide is one of the important precursors of NAD+, and supplementing NAD + Precursors are essential for restoring and maintaining intracellular NAD + There are currently studies on the role of niacinamide supplementation in the prevention and treatment of oral and systemic diseases, but there are relatively few products that add niacinamide as a nutritional supplement to oral health products.

[0004] Vitamin C has poor stability when formulated into oral preparations, while niacinamide has limited bioavailability when added directly. Mixing the two may also present compatibility issues. Therefore, a new technology is urgently needed to simultaneously enhance the stability of vitamin C and the bioavailability of niacinamide. Summary of the Invention

[0005] In order to develop a vitamin C product with good water solubility and high bioavailability, the present invention provides a vitamin C niacinamide cocrystal and a preparation method and application thereof.

[0006] In order to achieve the above technical objectives, the technical solutions adopted by the present invention are as follows:

[0007] In a first aspect of the present invention, there is provided an oral composition containing vitamin C and nicotinamide cocrystal, characterized in that it comprises, by weight:

[0008] 15-35 parts of Vitamin C niacinamide cocrystal;

[0009] Active polysaccharide 8-20 parts;

[0010] 3-10 parts of phosphatidylserine;

[0011] 2-8 parts of natural calming ingredients;

[0012] Astaxanthin 0.1-1 part;

[0013] Prebiotic oligosaccharides 20-40 parts;

[0014] Lactoferrin 1-5 parts;

[0015] Vitamin D3 0.01-0.1 parts;

[0016] 5-15 parts of amino acids and their derivatives;

[0017] The vitamin C nicotinamide cocrystal is a crystalline solid formed by weak interaction forces such as intermolecular hydrogen bonds between vitamin C and nicotinamide. The vitamin C nicotinamide cocrystal is prepared by mixing and dissolving vitamin C and nicotinamide, and then freeze-drying to remove the solvent.

[0018] Furthermore, the active polysaccharide is selected from one or more of Ganoderma lucidum polysaccharide, Lycium barbarum polysaccharide, and β-glucan.

[0019] Furthermore, the natural sedative ingredient is selected from one or more of jujube seed extract, valerian extract, and passionflower extract.

[0020] Furthermore, the prebiotic oligosaccharide is selected from one or more of fructooligosaccharides, inulin, and galacto-oligosaccharides.

[0021] Furthermore, the prebiotic oligosaccharide is fructooligosaccharide.

[0022] Furthermore, the amino acid and its derivatives are selected from one or more of magnesium glycinate, magnesium lysine, L-theanine, L-tryptophan, tyrosine, and γ-aminobutyric acid.

[0023] Furthermore, the amino acids and their derivatives are magnesium glycinate and L-theanine.

[0024] Furthermore, the astaxanthin is derived from Haematococcus pluvialis, krill or synthetic astaxanthin, preferably from Haematococcus pluvialis.

[0025] The second aspect of the present invention provides a method for preparing an oral composition containing vitamin C and nicotinamide cocrystal, characterized in that:

[0026] S1: Dissolve 15-35 parts of vitamin C nicotinamide cocrystal, 8-20 parts of active polysaccharide, 3-10 parts of phosphatidylserine, 2-8 parts of natural sedative ingredients, 20-40 parts of prebiotic oligosaccharides, 1-5 parts of lactoferrin, 0.1-1 part of astaxanthin, 0.01-0.1 part of vitamin D3, and 5-15 parts of amino acids and their derivatives in a solvent, stir well, and obtain a premixed solution.

[0027] S2: emulsifying and homogenizing the premixed solution by a homogenizer and sieving;

[0028] S3 uses spray drying technology to spray dry the sieved solution, with the inlet air temperature set at 80-90°C and the outlet air temperature set at 40-50°C.

[0029] The third aspect of the present invention provides the use of the above-mentioned oral composition containing vitamin C and nicotinamide cocrystal in the preparation of food, medicine and health care products.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] 1. In an oral composition containing vitamin C and niacinamide cocrystal disclosed in the present invention, vitamin C and niacinamide are bound by weak interactions such as hydrogen bonds and exist in the form of a cocrystal, which can improve the stability of vitamin C, enhance the bioavailability of niacinamide, and enhance the synergistic antioxidant effect of the two.

[0032] 2. The oral composition containing vitamin C nicotinamide cocrystal disclosed in the present invention takes vitamin C nicotinamide cocrystal as the core and is combined with multi-dimensional regulatory ingredients for immunity, nerves, and intestines to provide multiple functions in nutritional supplementation, anti-oxidation, sleep regulation, immune enhancement, health maintenance, etc.

[0033] 3. The preparation method of an oral composition containing vitamin C nicotinamide cocrystal disclosed in the present invention has a fast drying speed, a low temperature, a small impact on the active ingredients, is easy to scale up, and is convenient for large-scale production. The obtained powder has good dispersibility and is convenient for subsequent applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is a comparison chart of the scavenging rates of DPPH free radicals by different compositions of the present invention;

[0035] Figure 2 The different compositions of the present invention are + Comparison chart of free radical scavenging rates. DETAILED DESCRIPTION

[0036] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those skilled in the art without making creative work are within the scope of protection of the present invention. Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as those commonly understood by those skilled in the art in the technical field of the present invention. The terms used in the description of the present invention in this specification are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The experimental methods in the following examples, unless otherwise specified, are conventional methods. The experimental materials in the following examples, unless otherwise specified, are purchased from conventional biochemical reagent stores.

[0037] In order to make the purpose, technical solutions and advantages of the present invention more clear and distinct, the present invention is further described in detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0038] Nicotinamide, a component of coenzyme I and coenzyme II, plays a hydrogen transporter role in the biological oxidative respiratory chain, promoting biological oxidation processes and tissue metabolism. It plays an important role in maintaining the integrity of normal tissues, particularly the skin, digestive tract, and nervous system. Nicotinamide can be synthesized from tryptophan in the human body, but the efficiency is extremely low, so it must be ingested exogenously. Nicotinamide is used in food for a variety of purposes, primarily related to nutritional enhancement, health maintenance, beauty and skin care, and as an aid in food processing. Nicotinamide is one of the 13 essential vitamins and a member of the B vitamin complex. It is a key substance in human energy metabolism. It can be converted into NAD+ (nicotinamide adenine dinucleotide) in the human body and participates in cellular energy metabolism. It is a catalyst for energy production processes such as the tricarboxylic acid cycle and oxidative phosphorylation, providing energy for various physiological activities of the human body. Furthermore, nicotinamide is a component of the neurotransmitters NAD and NADP, which play a vital role in the normal functioning of the nervous system.

[0039] Co-crystal technology is an innovative drug development strategy that does not change the chemical structure of the original compound, but optimizes its physical and chemical properties through physical means, such as improving solubility, enhancing stability and improving bioavailability. This method can play a synergistic therapeutic and toxicity-reducing and efficacy-enhancing role.

[0040] An oral composition containing vitamin C nicotinamide cocrystal, characterized by comprising, by weight:

[0041] 15-35 parts of Vitamin C niacinamide cocrystal;

[0042] Active polysaccharide 8-20 parts;

[0043] 3-10 parts of phosphatidylserine;

[0044] 2-8 parts of natural calming ingredients;

[0045] Astaxanthin 0.1-1 part;

[0046] Prebiotic oligosaccharides 20-40 parts;

[0047] Lactoferrin 1-5 parts;

[0048] Vitamin D3 0.01-0.1 parts;

[0049] 5-15 parts of amino acids and their derivatives;

[0050] The composition is based on vitamin C niacinamide cocrystal, and is combined with immune-enhancing ingredients: active polysaccharides, lactoferrin, vitamin D3, nerve function-improving ingredients: phosphatidylserine, sleep-regulating ingredients: natural sedative ingredients, amino acids and their derivatives, and synergistic auxiliary ingredients: astaxanthin, prebiotic oligosaccharides, which together play a role in supplementing nutrition, regulating immunity, and improving nerve functions.

[0051] The vitamin C nicotinamide cocrystal is a crystalline solid formed by vitamin C and nicotinamide through weak interaction forces such as intermolecular hydrogen bonds. The vitamin C nicotinamide cocrystal is prepared by mixing and dissolving vitamin C and nicotinamide, and then freeze-drying to remove the solvent.

[0052] The co-crystal is prepared by freeze-drying, which has a low preparation temperature and less contact with oxygen during the preparation process, which can effectively reduce the damage to the activity of vitamin C and obtain more active vitamin C niacinamide co-crystal.

[0053] Preferably, the active polysaccharide is selected from one or more of Ganoderma lucidum polysaccharide, Lycium barbarum polysaccharide, and β-glucan. Preferably, the active polysaccharide is β-glucan.

[0054] Bioactive polysaccharides are a class of polysaccharides extracted from living organisms that possess biological and physiological activity and play a vital role in maintaining life. Carbohydrates not only serve as energy resources or structural materials, but some polysaccharides also participate in cellular metabolism and physiological regulation, exhibiting anti-tumor, lipid-lowering, antiviral, antioxidant, and immune-enhancing properties. β-glucan, with its high degree of branching and strong biological activity, possesses moisturizing, antioxidant, immunomodulatory, and anti-inflammatory properties.

[0055] Preferably, the natural sedative ingredient is selected from one or more of jujube seed extract, valerian extract, and passionflower extract. Preferably, the natural sedative ingredient is jujube seed extract.

[0056] Selecting natural sedative ingredients instead of synthetic sedatives like melatonin avoids disruptions in the body's melatonin synthesis and secretion rhythms caused by long-term melatonin use. Ziziphus jujuba seed extract regulates sleep-wake balance and exerts anti-insomnia effects by modulating the expression of neurotransmitters such as γ-aminobutyric acid (GABA)-ergic synaptic pathways, 5-hydroxytryptamine (5-HT)-ergic synaptic pathways, hypothalamic melanin-concentrating hormone (MCH), and orexin A in the hypothalamus. Ziziphus jujuba seed extract maintains energy metabolism and improves the brain's sleep rhythm regulation by regulating hypothalamic energy metabolism, improving liver metabolic function, regulating serum metabolite secretion, and improving myocardial mitochondrial function. Ziziphus jujuba seed alcohol extract can correct hypothalamic-pituitary-adrenal axis dysfunction, regulate the secretion of sleep-related hormones, regulate sleep structure, and exert a hypnotic effect. Ziziphus jujuba seed extract can improve immune function, significantly reduce the release of multiple inflammatory factors, and correct neuroendocrine-immune regulatory dysfunction to alleviate sleep disorders. Therefore, Ziziphus jujuba seed extract can improve sleep through multiple pathways and angles.

[0057] Preferably, the prebiotic oligosaccharide is selected from one or more of fructooligosaccharides, inulin, and galacto-oligosaccharides. Preferably, the prebiotic oligosaccharide is fructooligosaccharide.

[0058] Prebiotic oligosaccharides can promote the growth of beneficial intestinal flora. Fructo-oligosaccharides can regulate intestinal flora, promote the production of short-chain fatty acids, and form a synergistic "intestinal-immune axis" with lactoferrin. At the same time, fructo-oligosaccharides can also improve the sweetness and palatability.

[0059] Preferably, the amino acid and its derivatives are selected from one or more of magnesium glycinate, magnesium lysinate, L-theanine, L-tryptophan, tyrosine, and γ-aminobutyric acid. Preferably, the amino acid and its derivatives are magnesium glycinate and L-theanine.

[0060] Amino acids are essential for life, building proteins, participating in metabolic processes, and regulating physiological functions. The magnesium ions in magnesium glycinate and magnesium lysine promote the activation of vitamin D3. Amino acids like L-tryptophan, tyrosine, L-theanine, and gamma-aminobutyric acid relieve stress-related anxiety and improve concentration.

[0061] Preferably, the astaxanthin is derived from Haematococcus pluvialis, krill or synthetic astaxanthin, preferably from Haematococcus pluvialis.

[0062] Astaxanthin is renowned for its remarkable antioxidant capacity and is considered one of nature's strongest antioxidants. Haematococcus pluvialis is rich in astaxanthin, with concentrations ranging from 1.5% to 10.0%. It is recognized as the best organism for producing natural astaxanthin. Algal astaxanthin is the primary active ingredient in Haematococcus pluvialis.

[0063] The second aspect of the present invention provides a method for preparing an oral composition containing vitamin C and nicotinamide cocrystal, characterized in that:

[0064] S1: Dissolve 15-35 parts of vitamin C nicotinamide cocrystal, 8-20 parts of active polysaccharide, 3-10 parts of phosphatidylserine, 2-8 parts of natural sedative ingredients, 20-40 parts of prebiotic oligosaccharides, 1-5 parts of lactoferrin, 0.1-1 part of astaxanthin, 0.01-0.1 part of vitamin D3, and 5-15 parts of amino acids and their derivatives in a solvent, stir well, and obtain a premixed solution.

[0065] S2: emulsifying and homogenizing the premixed solution by a homogenizer and sieving;

[0066] S3 uses spray drying technology to spray dry the sieved solution, with the inlet air temperature set at 80-90°C and the outlet air temperature set at 40-50°C.

[0067] Homogenizer treatment evenly disperses fat-soluble and water-soluble ingredients, reducing phase separation and improving product stability. The inlet air temperature of 80-90°C and the outlet air temperature of 40-50°C are significantly lower than conventional spray drying temperatures (typically 160-200°C), effectively preventing oxidation or denaturation of heat-sensitive ingredients such as vitamin C, lactoferrin, and astaxanthin. Spray drying takes a short time and rapidly evaporates water, preventing ingredient inactivation caused by prolonged drying. It also directly produces a fluid powder, eliminating the need for subsequent granulation.

[0068] The third aspect of the present invention provides the use of the above-mentioned oral composition containing vitamin C and nicotinamide cocrystal in the preparation of food, medicine and health care products.

[0069] The present invention is explained in detail below with reference to the examples.

[0070] Experimental Example 1

[0071] This embodiment provides an oral composition containing vitamin C niacinamide cocrystal, comprising the following raw materials in parts by weight:

[0072] Vitamin C niacinamide cocrystal 30 parts;

[0073] 12 parts of β-glucan;

[0074] Phosphatidylserine 7 parts;

[0075] 4 parts of Suanzaorensis Seed Extract;

[0076] Astaxanthin 0.3 parts;

[0077] 30.65 parts of oligofructose;

[0078] 4 servings of lactoferrin

[0079] Vitamin D3 0.05 parts;

[0080] 6 parts of magnesium glycinate;

[0081] 6 parts of L-theanine;

[0082] Among them, the preparation method of vitamin C nicotinamide cocrystal is as follows: nicotinamide and vitamin C in a mass ratio of 1:1.5 are completely dissolved in water, pre-frozen at -80°C and then placed in a vacuum freeze dryer for freeze drying to obtain a vitamin C nicotinamide cocrystal solid. The PXRD diffraction of the cocrystal has diffraction angles 2θ of 5.54°±0.2°, 10.69°±0.2°, 13.09°±0.2°, 16.68°±0.2°, and 21.05°±0.2°.

[0083] The above substances were dissolved in twice the mass of water and stirred to obtain a premix solution. The premix solution was emulsified and homogenized in a homogenizer, passed through an 80-mesh sieve, and then spray-dried with the air inlet temperature set at 85°C and the air outlet temperature set at 42°C to obtain an oral composition containing vitamin C and niacinamide cocrystals.

[0084] Experimental Example 2

[0085] This embodiment provides an oral composition containing vitamin C niacinamide cocrystal, comprising the following raw materials in parts by weight:

[0086] Vitamin C niacinamide cocrystal 35 parts;

[0087] 5 parts of Ganoderma lucidum polysaccharide;

[0088] 7 servings of Lycium barbarum polysaccharides

[0089] 8 parts of phosphatidylserine;

[0090] 3 parts of Suanzaorensis seed extract;

[0091] Astaxanthin 0.5 parts;

[0092] 25.44 parts of galacto-oligosaccharide;

[0093] 5 servings of lactoferrin

[0094] Vitamin D3 0.06 parts;

[0095] 7 parts of magnesium lysine;

[0096] 4 parts of γ-aminobutyric acid;

[0097] Among them, the preparation method of vitamin C nicotinamide cocrystal is as follows: nicotinamide and vitamin C with a mass ratio of 1:1.5 are completely dissolved in ethanol water (the mass ratio of ethanol to water is 10:90), pre-frozen at -80°C and then placed in a vacuum freeze dryer for freeze drying to obtain vitamin C nicotinamide cocrystal solid.

[0098] The above substances were dissolved in twice the mass of water and stirred to obtain a premix solution. The premix solution was emulsified and homogenized in a homogenizer, passed through an 80-mesh sieve, and then spray-dried with the air inlet temperature set at 90°C and the air outlet temperature set at 40°C to obtain an oral composition containing vitamin C and niacinamide cocrystals.

[0099] Experimental Example 3

[0100] This embodiment provides an oral composition containing vitamin C niacinamide cocrystal, comprising the following raw materials in parts by weight:

[0101] Vitamin C niacinamide cocrystal 15 parts;

[0102] 5 parts of Ganoderma lucidum polysaccharide;

[0103] 13 parts of β-glucan;

[0104] Phosphatidylserine 7 parts;

[0105] 5 parts of Suanzaorensis seed extract;

[0106] Astaxanthin 0.8 parts;

[0107] 18.1 parts of oligofructose;

[0108] Inulin 20 parts;

[0109] 4 servings of lactoferrin

[0110] Vitamin D3 0.1 part;

[0111] 7 parts of magnesium lysine;

[0112] 5 parts of L-tryptophan;

[0113] Among them, the preparation method of vitamin C nicotinamide cocrystal is as follows: nicotinamide and vitamin C with a mass ratio of 1:1.5 are completely dissolved in water, pre-frozen at -80°C and then placed in a vacuum freeze dryer for freeze drying to obtain vitamin C nicotinamide cocrystal solid.

[0114] The above substances were dissolved in 3 times the mass of water and stirred to obtain a premix solution. The premix solution was emulsified and homogenized in a homogenizer, passed through a 100-mesh sieve, and then spray-dried with the air inlet temperature set at 80°C and the air outlet temperature set at 50°C to obtain an oral composition containing vitamin C and niacinamide cocrystals.

[0115] Comparative Example 1

[0116] An oral composition comprising the following raw materials in parts by weight:

[0117] Vitamin C 15 parts;

[0118] 15 parts of niacinamide;

[0119] 12 parts of β-glucan;

[0120] Phosphatidylserine 7 parts;

[0121] 4 parts of Suanzaorensis Seed Extract;

[0122] Astaxanthin 0.3 parts;

[0123] 30.65 parts of oligofructose;

[0124] 4 servings of lactoferrin

[0125] Vitamin D3 0.05 parts;

[0126] 6 parts of magnesium glycinate;

[0127] 6 parts of L-theanine;

[0128] The above substances were dissolved in 2 times the mass of water and stirred to obtain a premix solution. The premix solution was emulsified and homogenized by a homogenizer, passed through an 80-mesh sieve, and then spray-dried with the air inlet temperature set at 85°C and the air outlet temperature set at 42°C to obtain an oral composition.

[0129] Comparative Example 2

[0130] An oral composition comprising the following raw materials in parts by weight:

[0131] Vitamin C niacinamide cocrystal 30 parts;

[0132] 12 parts of β-glucan;

[0133] Phosphatidylserine 7 parts;

[0134] 4 parts of Suanzaorensis Seed Extract;

[0135] Astaxanthin 0.3 parts;

[0136] 30.65 parts of oligofructose;

[0137] 4 servings of lactoferrin

[0138] Vitamin D3 0.05 parts;

[0139] 6 parts of magnesium glycinate;

[0140] 6 parts of L-theanine;

[0141] Among them, the preparation method of vitamin C nicotinamide cocrystal is as follows: nicotinamide and vitamin C with a mass ratio of 1:1.5 are completely dissolved in water, pre-frozen at -80°C and then placed in a vacuum freeze dryer for freeze drying to obtain vitamin C nicotinamide cocrystal solid.

[0142] The above substances were dissolved in 2 times the mass of water and stirred to obtain a premix solution. The premix solution was emulsified and homogenized by a homogenizer, passed through an 80-mesh sieve, and then spray-dried with the air inlet temperature set to 170°C and the air outlet temperature set to 80°C to obtain an oral composition.

[0143] Comparative Example 3

[0144] An oral composition comprising the following raw materials in parts by weight:

[0145] Vitamin C 15 parts;

[0146] 12 parts of β-glucan;

[0147] Phosphatidylserine 7 parts;

[0148] 4 parts of Suanzaorensis Seed Extract;

[0149] Astaxanthin 0.3 parts;

[0150] 30.65 parts of oligofructose;

[0151] 4 servings of lactoferrin

[0152] Vitamin D3 0.05 parts;

[0153] 6 parts of magnesium glycinate;

[0154] 6 parts of L-theanine;

[0155] 15 parts starch

[0156] The above substances were dissolved in 2 times the mass of water and stirred to obtain a premix solution. The premix solution was emulsified and homogenized by a homogenizer, passed through an 80-mesh sieve, and then spray-dried with the air inlet temperature set at 85°C and the air outlet temperature set at 42°C to obtain an oral composition.

[0157] Comparative Example 4

[0158] An oral composition comprising the following raw materials in parts by weight:

[0159] 15 parts of niacinamide;

[0160] 12 parts of β-glucan;

[0161] Phosphatidylserine 7 parts;

[0162] 4 parts of Suanzaorensis Seed Extract;

[0163] Astaxanthin 0.3 parts;

[0164] 30.65 parts of oligofructose;

[0165] 4 servings of lactoferrin

[0166] Vitamin D3 0.05 parts;

[0167] 6 parts of magnesium glycinate;

[0168] 6 parts of M-theanine;

[0169] 15 parts starch

[0170] The above substances were dissolved in 2 times the mass of water and stirred to obtain a premix solution. The premix solution was emulsified and homogenized by a homogenizer, passed through an 80-mesh sieve, and then spray-dried with the air inlet temperature set at 85°C and the air outlet temperature set at 42°C to obtain an oral composition.

[0171] Test Example 1

[0172] Pharmacokinetic testing of vitamin C

[0173] Pharmacokinetics of the vitamin C nicotinamide cocrystal obtained in Experimental Example 1 of the present invention and the control vitamin C were tested

[0174] 1. Experimental materials and methods:

[0175] 1.1 Drug preparation and plasma sample preparation

[0176] 20g mice were gavaged with 2.56mg of vitamin C nicotinamide cocrystal sample (128mg / kg, containing 1.5mg of vitamin C) and 1.5mg of control vitamin C. Blood was collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, and 16h, respectively. The blood was centrifuged in a high-speed refrigerated centrifuge for 15min (3500rpm, 4°C), and the supernatant was collected for testing.

[0177] 1.2 Configuration of Standard Products

[0178] Vitamin C standard was prepared into 80 mg / L using blank serum. 50 μL of standard was added to 50 μL of 10 parts of metaphosphoric acid solution, 100 μL of 25 mmol / L sodium dihydrogen phosphate solution, and 200 μL of 4 g / L dithiothreitol in 10 parts of metaphosphoric acid solution. The mixture was vortexed for 20 s, allowed to stand at 4°C for 10 min, and centrifuged in a high-speed refrigerated centrifuge for 15 min (3500 rpm, 4°C). The supernatant was collected and filtered through a nylon membrane (φ=0.45 μm). 10 μL of the supernatant was injected for measurement.

[0179] 1.3 Sample configuration

[0180] Take 50 μL of sample plasma, add 50 μL of 10 parts of metaphosphoric acid solution, and prepare the sample according to the preparation method of the standard.

[0181] 1.4 Data Analysis

[0182] Excel was used to draw the standard curve, and the sample concentration in serum was calculated based on the peak area. Phoenix Win Nonlin 8.1 pharmacokinetic analysis software was then used to fit the area under the plasma concentration-time curve (AUC), maximum concentration (Cmax, mg / L), and time to peak (Tmax, h) according to the NCA standard model. GraphPad Prism 8.1 software was used for data processing and graphing.

[0183] 2. Experimental Results

[0184] Table 1: AUC, Cmax, Tmax and Relative absorption of vitamin C-treated groups

[0185]

[0186] The sample measurement results are shown in Table 1. The AUCs of vitamin C niacinamide cocrystal and the control vitamin C were 10.44 and 6.46 h*mg / L, respectively. The Cmax of vitamin C niacinamide cocrystal and the control vitamin C were 1.66 and 1.23 mg / L, respectively. The Tmax of vitamin C niacinamide cocrystal and the control vitamin C were 1.08 and 1.17 h, respectively. The relative bioavailability of vitamin C niacinamide cocrystal and the control vitamin C was 1.6 and 1. The bioavailability of vitamin C niacinamide cocrystal was significantly higher than that of the vitamin C control group.

[0187] Test Example 2

[0188] Pharmacokinetic testing of nicotinamide

[0189] Pharmacokinetics of the vitamin C nicotinamide cocrystal and the control nicotinamide obtained in Experimental Example 1 of the present invention were tested

[0190] 1. Experimental materials and methods:

[0191] 1.1 Drug preparation and plasma sample preparation

[0192] 20g mice were gavaged with 2.56mg of vitamin C nicotinamide cocrystal sample (128mg / kg, containing 1.05mg of nicotinamide), 25.66mg of high-dose vitamin C nicotinamide cocrystal sample (1280mg / kg, containing 10.5mg of nicotinamide), and 1.005mg of control nicotinamide. Blood was collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, and 16h, respectively. The blood was centrifuged in a high-speed refrigerated centrifuge for 15min (3500rpm, 4°C), and the supernatant was collected for testing.

[0193] 1.2 Configuration of Standard Products

[0194] Nicotinamide standards were prepared with blank serum to concentrations of 320, 160, 80, 40, 20, 10, 5, and 2.5 mg / L. 50 μL of the standard was added to 320 μL of mobile phase, vortexed for 20 s, allowed to stand at 4°C for 10 min, and centrifuged in a high-speed refrigerated centrifuge for 20 min (3500 rpm, 4°C). The supernatant was collected and filtered through a nylon membrane (φ=0.45 μm). 10 μL of the sample was injected for measurement.

[0195] 1.3 Sample configuration

[0196] Take 80 μL of sample plasma, add 320 μL of mobile phase, and prepare the sample according to the preparation method of the standard.

[0197] 1.4 Data Analysis

[0198] Excel was used to draw the standard curve, and the sample concentration in serum was calculated based on the peak area. Phoenix Win Nonlin 8.1 pharmacokinetic analysis software was then used to fit the area under the plasma concentration-time curve (AUC), maximum concentration (Cmax, mg / L), and time to peak (Tmax, h) according to the NCA standard model. GraphPad Prism 8.1 software was used for data processing and graphing.

[0199] 2. Experimental Results

[0200] Table 2: AUC, Cmax, Tmax and Relative absorption of vitamin C-treated groups

[0201]

[0202] The sample analysis results are shown in Table 2. To investigate the bioavailability of niacinamide and the bioavailability of vitamin C niacinamide cocrystals at different concentrations, a high-dose vitamin C niacinamide cocrystal sample group was also included. The AUCs for vitamin C niacinamide cocrystals, high-dose vitamin C niacinamide cocrystals, and the control niacinamide were 153.21, 1671.46, and 60.90 h*mg / L, respectively. The Cmax values ​​for vitamin C niacinamide cocrystals, high-dose vitamin C niacinamide cocrystals, and the control niacinamide were 25.85, 312.42, and 23.12 mg / L, respectively. The Tmax values ​​for vitamin C niacinamide cocrystals, high-dose vitamin C niacinamide cocrystals, and the control niacinamide were 0.42, 0.42, and 0.58 h, respectively. The relative availabilities of vitamin C niacinamide cocrystals, high-dose vitamin C niacinamide cocrystals, and the control niacinamide were 2.57, 2.74, and 1, respectively. The bioavailability of vitamin C niacinamide cocrystals was significantly higher than that of the niacinamide control group. When the concentration of vitamin C niacinamide cocrystal increases, the bioavailability remains high.

[0203] Test Example 3

[0204] Stability testing of oral compositions containing vitamin C and nicotinamide cocrystals

[0205] The oral compositions containing vitamin C nicotinamide cocrystal obtained in Experimental Example 1, Experimental Example 2, and Experimental Example 3 and the oral compositions obtained in Comparative Example 1 and Comparative Example 2 were placed in aluminum foil bags and subjected to destructive and stability tests.

[0206] Table 3: High temperature 60℃ destructive test results

[0207]

[0208]

[0209] Table 4: High temperature 45℃ accelerated test results

[0210]

[0211]

[0212] The oral compositions containing vitamin C and niacinamide cocrystals obtained in Experimental Examples 1, 2, and 3 exhibited significant state changes in both the 60°C destructive test and the 45°C accelerated test, demonstrating high stability. The oral composition in Comparative Example 1, in which vitamin C and niacinamide existed as monomers, darkened and deepened in color over time in both the 60°C destructive test and the 45°C accelerated test. This demonstrates that the formation of a cocrystal between vitamin C and niacinamide improves stability. The oral composition in Comparative Example 2 was prepared at a high temperature, resulting in a dark yellow composition, demonstrating that processing temperature affects product state and causes some damage to heat-sensitive components. The oral composition in Comparative Example 2 did not undergo significant state changes in the 60°C destructive test, but darkened in color over time in the 45°C accelerated test, demonstrating that excessively high processing temperatures can affect product stability.

[0213] Test Example 4

[0214] DPPH free radical scavenging test of oral composition containing vitamin C nicotinamide cocrystal

[0215] 1. Experimental Principle

[0216] 1,1-Diphenyl-2-trinitrophenylhydrazine (DPPH) is a stable, long-lived free radical. Its ethanol solution appears dark purple and exhibits strong absorption near 517nm. In the presence of free radical scavengers, the light absorption of DPPH ethanol solutions is reduced due to pairing with its single electron. The degree of discoloration of DPPH ethanol solutions is linearly related to the number of electrons accepted, which can be used to evaluate the free radical scavenging ability of the test sample, i.e., its antioxidant activity.

[0217] 2. Experimental Procedures

[0218] Set up sample tubes (T), sample backgrounds (T0), DPPH tubes (C), and solvent backgrounds (C0). For each test concentration of each sample, three parallel tubes of sample tubes (T) should be set up. Add 1 mL of the same concentration of sample solution to each of the sample tubes (T) and the sample backgrounds (T0). Add the sample solvent to the sample backgrounds (T0) and the solvent backgrounds (C0) to make up 2 mL, and mix well. Add 1 mL of DPPH ethanol solution to the sample tubes (T) and the DPPH tubes (C), shake gently, and let stand at room temperature for 5 min. Transfer the solution of each reaction tube into a 1-cm cuvette and measure the absorbance at 517 nm.

[0219]

[0220] 3. Experimental Results

[0221] Table 5 Scavenging Rates of Different Combinations on DPPH Free Radicals

[0222]

[0223]

[0224] Statistical method: The t-test method was used for analysis, and the significance level α = 0.05; P ≥ 0.05 indicates no statistical difference; 0.01 < P < 0.05 indicates a significant difference; P < 0.01 indicates a very significant difference; P < 0.001 indicates an extremely significant difference.

[0225] According to the results in Table 5, the oral compositions containing the co-crystal of vitamin C and niacinamide in Experimental Example 1, the oral composition in Comparative Example 1, and the oral composition in Comparative Example 2 all have the effect of scavenging DPPH free radicals. At the same concentration, the effect of the oral composition containing the co-crystal of vitamin C and niacinamide in Experimental Example 1 is better than that of the oral compositions in Comparative Example 1, Comparative Example 2, Comparative Example 3, and Comparative Example 4, proving that the oral composition containing the co-crystal of vitamin C and niacinamide has better antioxidant ability.

[0226] Test Example 5

[0227] ABTS Free Radical Scavenging Test of Oral Composition Containing Co-Crystal of Vitamin C and Niacinamide +

[0228] 1. Experimental Principle

[0229] When an oxidant is present, ABTS will be oxidized to ABTS + free radicals, and the solution will turn green and have a strong absorption at a wavelength of 734 nm in the ultraviolet region. When an antioxidant is added to the system, ABTS + ​The production amount will decrease, the solution color will become lighter, gradually changing from dark green to light green, and the absorbance at 734 nm will become smaller, thereby determining the ABTS of this substance + free radical scavenging rate.

[0230] 2. Experimental procedures

[0231] Set up sample tubes (A S ), sample backgrounds (A b ), and sample blank tubes (A0). For each test concentration of each sample, 3 parallel tubes of the sample tube (A S ) need to be set up, and at the same time, 3 parallel tubes of the sample blank tube (A0) also need to be set up. Add 0.2 mL of the same concentration of sample solution to the sample tube (A S ) and the sample background (A b ), and add 0.2 mL of PBS buffer to the sample blank tube (A0). Add 0.8 mL of ABTS S working solution to the sample tube (A + ) and the sample blank tube (A0), and add 0.8 mL of PBS buffer to the sample background (A b ). React for 6 min in the dark. Transfer the solution in each reaction tube to a 1 cm cuvette and measure the absorbance at 734 nm.

[0232]

[0233] 3. Experimental results

[0234] Table 5 Scavenging rates of different compositions on ABTS + free radicals

[0235]

[0236] Statistical method: Analyze using the t-test method, with the test level α = 0.05; P ≥ 0.05 indicates no statistical difference; 0.01 < P < 0.05 indicates a significant difference; P < 0.01 indicates a very significant difference; P < 0.001 indicates an extremely significant difference.

[0237] According to the results in Table 6, the oral compositions containing the vitamin C-nicotinamide cocrystal in Experimental Example 1, the oral composition in Comparative Example 1, and the oral composition in Comparative Example 2 all have the effect of scavenging ABTS + free radicals. At the same concentration, the effect of the oral composition containing the vitamin C-nicotinamide cocrystal in Experimental Example 1 is better than that of the oral compositions in Comparative Example 1, Comparative Example 2, Comparative Example 3, and Comparative Example 4, proving that the oral composition containing the vitamin C-nicotinamide cocrystal has better antioxidant ability.

[0238] The above are all preferred embodiments of the present invention, and are not intended to limit the scope of protection of the present invention. Therefore, any equivalent changes made based on the mechanism, shape, and principle of the present invention should be included in the scope of protection of the present invention.

Claims

1. An oral composition containing vitamin C nicotinamide cocrystal, characterized in that: The formula includes, by weight: 15-35 parts of vitamin C niacinamide cocrystal; Active polysaccharide 8-20 parts; 3-10 parts of phosphatidylserine; 2-8 parts of natural calming ingredients; Astaxanthin 0.1-1 part; Prebiotic oligosaccharides 20-40 parts; Lactoferrin 1-5 parts; Vitamin D3 0.01-0.1 parts; 5-15 parts of amino acids and their derivatives; The vitamin C nicotinamide cocrystal is a crystalline solid formed by vitamin C and nicotinamide through weak interaction forces such as intermolecular hydrogen bonds. The vitamin C nicotinamide cocrystal is prepared by mixing and dissolving vitamin C and nicotinamide, and then freeze-drying to remove the solvent.

2. The oral composition containing vitamin C nicotinamide cocrystal according to claim 1, characterized in that: The active polysaccharide is selected from one or more of ganoderma lucidum polysaccharide, wolfberry polysaccharide and β-glucan.

3. The oral composition containing vitamin C nicotinamide cocrystal according to claim 1, characterized in that: The natural sedative ingredient is selected from one or more of jujube seed extract, valerian extract, and passionflower extract.

4. The oral composition containing vitamin C nicotinamide cocrystal according to claim 1, characterized in that: The prebiotic oligosaccharide is selected from one or more of fructooligosaccharides, inulin and galacto-oligosaccharides.

5. The oral composition containing vitamin C nicotinamide cocrystal according to claim 1, characterized in that: The prebiotic oligosaccharide is fructooligosaccharide.

6. The oral composition containing vitamin C nicotinamide cocrystal according to claim 1, characterized in that: The amino acid and its derivatives are selected from one or more of magnesium glycinate, magnesium lysine, L-theanine, L-tryptophan, tyrosine, and gamma-aminobutyric acid.

7. The oral composition containing vitamin C nicotinamide cocrystal according to claim 1, characterized in that: The amino acids and their derivatives are magnesium glycinate and L-theanine.

8. The oral composition containing vitamin C nicotinamide cocrystal according to claim 1, characterized in that: The astaxanthin is sourced from Haematococcus pluvialis, krill or synthetic astaxanthin, preferably from Haematococcus pluvialis.

9. A method for preparing the oral composition containing vitamin C and nicotinamide cocrystal according to claim 1, characterized in that: S1: Dissolve 15-35 parts of vitamin C niacinamide cocrystal, 8-20 parts of active polysaccharide, 3-10 parts of phosphatidylserine, 2-8 parts of natural sedative ingredients, 20-40 parts of prebiotic oligosaccharides, 1-5 parts of lactoferrin, 0.1-1 part of astaxanthin, 0.01-0.1 part of vitamin D3, and 5-15 parts of amino acids and their derivatives in a solvent, and stir evenly to obtain a premixed solution. S2: emulsifying and homogenizing the premixed solution by a homogenizer and sieving; S3 uses spray drying technology to spray dry the sieved solution, with the inlet air temperature set at 80-90°C and the outlet air temperature set at 40-50°C.

10. Use of the oral composition containing vitamin C and nicotinamide cocrystal according to claim 1 in the preparation of food, medicine, and health care products.

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