Creatine compound B vitamin composition and preparation method thereof

Abstract

The invention provides a creatine compound B vitamin composition and a preparation method thereof. The creatine compound B vitamin composition is prepared from the following raw materials in parts by weight: 50 to 70 parts of creatine monohydrate, 4 to 20 parts of compound B vitamin microcapsules, 15 to 40 parts of silicified microcrystalline cellulose (SMCC) and 0.5 to 1.5 parts of magnesium stearate. The creatine and the vitamins play a synergistic role, the compatibility and the stability of all the components are remarkably improved by optimizing the composition and the proportion of the raw materials and combining a special preparation process, and the bioavailability of the creatine is improved. The composition provided by the invention can effectively improve athletic performance, promote muscle recovery and meet nutritional requirements of different people.

Description

Technical Field

[0001] This invention belongs to the field of sports nutrition supplement technology, specifically relating to a creatine-based B vitamin composition and its preparation method. Background Technology

[0002] Creatine is a nitrogenous organic acid naturally found in vertebrates, primarily in muscle tissues such as skeletal and cardiac muscles. Creatine increases the content of creatine phosphate in muscles, which is a reserve form of adenosine triphosphate (ATP), the direct energy source required for muscle contraction. 95% of the body's creatine is stored in skeletal muscle, and rapid ATP replenishment enhances muscle power and endurance. Studies have shown that creatine supplementation can increase creatine phosphate levels in muscles by 15-40%, significantly improving high-intensity exercise performance. However, creatine, when used alone, suffers from low absorption and poor stability.

[0003] B vitamins play a crucial role in energy metabolism. Vitamin B1 participates in carbohydrate metabolism, B2 participates in redox reactions, B6 promotes amino acid utilization, and B12 supports erythrocyte production. In the prior art, patent document CN106805227A discloses a nutritional fortifier containing creatine and a complex of vitamins; however, this patent does not provide solutions to the stability problems encountered during vitamin preparation, nor does it address the compatibility and stability issues of the various components.

[0004] Traditional creatine preparations suffer from the following technical defects: (1) ordinary creatine monohydrate is easily degraded under humid and hot conditions; (2) B vitamins are easily lost during processing; (3) different components have large differences in solubility and stability, affecting the uniformity of the preparation; and (4) creatine has a low absorption rate. Therefore, developing a creatine-multivitamin composition with high stability, high bioavailability, and good compatibility among its components has important application value. Summary of the Invention

[0005] Creatine has been extensively studied as a supplement to improve athletic performance, but it suffers from problems such as low absorption rate and easy degradation. Research on the synergistic effect of vitamins and creatine is limited, and existing compound formulations often exhibit defects such as component instability and insufficient bioavailability. Traditional preparation methods easily lead to loss of heat sensitivity or incompatibility of physical properties. To address the shortcomings of existing technologies, this invention provides a creatine compound with B vitamins (B1, B2, B6, B12) and its preparation method. This invention allows creatine and vitamins to work synergistically. By optimizing the raw material composition and ratio, combined with a special preparation process, the compatibility and stability of each component are significantly improved, thereby increasing the bioavailability of creatine. The composition of this invention can effectively improve athletic performance, promote muscle recovery, and meet the nutritional needs of different populations.

[0006] This invention is achieved through the following technical solution: A creatine complex B vitamin composition comprises the following raw materials in parts by weight: 50-70 parts creatine monohydrate, 4-20 parts complex B vitamin microcapsules, 15-40 parts silicified microcrystalline cellulose (SMCC), and 0.5-1.5 parts magnesium stearate.

[0007] According to a preferred embodiment of the present invention, the creatine complex B vitamin composition comprises the following raw materials in parts by weight: 50-70 parts of creatine monohydrate, 4.2-15 parts of complex B vitamin microcapsules, 24-34.5 parts of silicified microcrystalline cellulose (SMCC), and 0.8-1.5 parts of magnesium stearate.

[0008] According to a preferred embodiment of the present invention, the particle size of creatine monohydrate is less than or equal to 80 mesh. The creatine is selected in monohydrate form with a purity ≥99.5% and a particle size less than or equal to 80 mesh, which ensures solubility while avoiding static electricity problems caused by excessively fine powder.

[0009] According to a preferred embodiment of the present invention, the compound B vitamin microcapsules are compound vitamin B1, vitamin B2, vitamin B6, and vitamin B12 microcapsules.

[0010] According to a preferred embodiment of the present invention, the preparation method of the compound B vitamin microcapsules includes the following steps: Octyl succinate-modified starch and maltodextrin are fully dissolved in water, and vitamins B1, B2, B6, and B12 or a mixture of vitamins B1, B2, B6, and B12 are added and mixed thoroughly. Then, the mixture is homogenized, emulsified, and spray-dried to obtain complex B vitamin microcapsules.

[0011] Preferably, the mass ratio of octyl succinate starch to maltodextrin is 1~3:1; the mass ratio of octyl succinate starch to water is 1:13.3~20, to prepare a wall material solution with a suitable solids concentration.

[0012] Preferably, after adding octyl succinate starch and maltodextrin to water, the mixture is stirred at 50–60°C for 30–60 minutes to ensure complete dissolution and hydration, forming a homogeneous colloidal solution.

[0013] Preferably, the mass ratio of vitamin B1, vitamin B2, vitamin B6, and vitamin B12 is (1.0-2.0):(1.0-2.0):(1.5-5.0):(0.002-0.02), and more preferably 1:1.50-1.67:1.67-5.0:0.0042-0.0083.

[0014] Preferably, the mass ratio of the total mass of vitamin B1, vitamin B2, vitamin B6, and vitamin B12 to the mass of octyl succinate starch is 22-31:100.

[0015] Preferably, the homogenization emulsification conditions are: homogenization 2–3 times at 50–100 MPa. Purpose: To form fine, uniform droplets (particle size <1–2 μm), improving encapsulation efficiency and stability. OSA starch plays an emulsifying role at this stage, reducing oil-water interfacial tension (stabilizing vitamin molecule aggregation even without an oil phase).

[0016] Preferably, the spray drying conditions are as follows: inlet air temperature: 150–170℃, feed rate: 10–20 mL / min. Free-flowing microcapsule powder is obtained after drying. The dried powder is collected by a cyclone separator and immediately cooled to room temperature. It is then sealed and stored in a desiccator, protected from light, to prevent moisture absorption.

[0017] According to a preferred embodiment of the present invention, the siliconized microcrystalline cellulose (SMCC) is at least one of Prosolv SMCC 90, Prosolv SMCC 90 LM, or Prosolv SMCC HD 90. Preferably, the siliconized microcrystalline cellulose (SMCC) is Prosolv SMCC 90 LM.

[0018] According to the present invention, the particle size D90 of magnesium stearate is preferably 10-30 μm, more preferably 12-25 μm, and most preferably 25 μm.

[0019] The preparation method of the above-mentioned creatine complex B vitamin composition includes the following steps: Creatine monohydrate and silicified microcrystalline cellulose (SMCC) are premixed; compound B vitamin microcapsules are added and mixed evenly; magnesium stearate is added and mixed thoroughly; then the mixture is compressed into tablets to obtain a creatine compound B vitamin composition.

[0020] According to a preferred embodiment of the present invention, the premixing time is 10-20 minutes and the premixing speed is 15-30 rpm.

[0021] According to a preferred embodiment of the present invention, after adding the compound B vitamin microcapsules, the mixture is stirred for 10-30 minutes at a speed of 15-25 rpm in an environment with a relative humidity of ≤40% and a mixing temperature of 20-25°C to ensure uniform mixing; preferably, the relative humidity is 20-40%.

[0022] According to a preferred embodiment of the present invention, after adding magnesium stearate, the mixture is stirred at a speed of 15 rpm-20 rpm for 5-10 minutes.

[0023] According to a preferred embodiment of the present invention, the tableting pressure is 30-50 kN, the tablet weight is controlled at 1.0-1.3 g, and the hardness is controlled at 30-80 N.

[0024] The technical features and beneficial effects of this invention are as follows: 1. At the raw material composition level, the specific ratio of B vitamins meets the metabolic needs of athletes. Vitamins B1, B2, and B6 participate in the tricarboxylic acid cycle (TCA cycle), helping to convert glucose into adenosine triphosphate (ATP) and synergistically enhancing energy supply with creatine. Vitamin B6 participates in amino acid metabolism, aiding in the synthesis and utilization of creatine in the body. Vitamin B12 participates in erythrocyte production and the maintenance of nervous system function, preventing exercise-induced fatigue and neurological decline. B vitamins also support nerve conduction and muscle contraction coordination.

[0025] 2. This invention utilizes microencapsulation to enhance the compatibility and stability of B vitamins. Vitamins B1, B2, B6, and B12 are mixed with a wall material (maltodextrin and octenyl succinate starch ester) in water to form an oil-in-water (W / O) emulsion. After homogenization to form a stable emulsion, the emulsion is spray-dried, causing rapid evaporation of water and forming solid microcapsule particles. The vitamins are encapsulated within the wall material and protected. Maltodextrin: High solubility, low cost, and good film-forming properties make it a commonly used filler wall material. OSA starch (octenyl succinate starch ester): Possesses surface activity, significantly reducing interfacial tension, improving emulsion stability, and enhancing barrier properties against heat, light, and oxygen, making it particularly suitable for encapsulating sensitive components.

[0026] 3. In the process of this invention, silicified microcrystalline cellulose is mixed with creatine to improve the mixing uniformity, stability and direct tableting performance of creatine powder.

[0027] 4. The creatine and vitamins in this invention work synergistically. By optimizing the raw material composition and ratio, combined with a special preparation process, the compatibility and stability of each component are significantly improved, thereby increasing the bioavailability of creatine. In accelerated stability tests (40℃±2℃, RH 75%±5%), the retention rate of each component exceeded 85% after 6 months, and the dissolution rate reached over 90% within 30 minutes. The composition of this invention can effectively improve athletic performance, promote muscle recovery, and meet the nutritional needs of different populations.

[0028] 5. The preparation method of the creatine-multivitamin composition provided by this invention is simple and suitable for industrial production, with the following advantages: i. Production feasibility: All conventional pharmaceutical equipment is used, requiring no special devices; process parameters are easy to control, with small batch-to-batch variations (RSD < 3%); the product production cycle is relatively short; ii. Quality control: A method for simultaneously determining the content of creatine and multiple vitamins by HPLC is established; indicators such as dissolution and content uniformity meet pharmacopoeia requirements; stability meets the 24-month shelf-life requirement; iii. Application prospects: Suitable for sports nutrition supplementation for athletes and fitness enthusiasts; used for the prevention of sarcopenia in middle-aged and elderly people; as an active ingredient in special medical purpose formula foods; can be developed into different dosage forms (tablets, capsules, granules, etc.). This invention solves the technical problem of poor compatibility and stability of creatine and multiple vitamins through scientific formulation design and optimized preparation process, providing a highly efficient, safe, and stable compound nutritional supplement with good market application prospects. Detailed Implementation

[0029] The present invention will be further described below with reference to the embodiments, but the present invention is not limited to the following embodiments.

[0030] Example 1 A creatine-based B-complex vitamin composition, comprising the following raw materials in parts by weight: Creatine monohydrate 60 parts, complex B vitamin microcapsules 7 parts, silicified microcrystalline cellulose 32 parts, magnesium stearate 1 part.

[0031] The particle size of creatine monohydrate is less than or equal to 80 mesh, the purity is 99.8%, and the D90 is about 90 μm.

[0032] The siliconized microcrystalline cellulose is designated Prosolv SMCC 90 LM, and the magnesium stearate has a particle size D90 of approximately 25 μm.

[0033] The preparation method of compound B vitamin microcapsules includes the following steps: (1) Wall materials are dispersed Add 100g of maltodextrin and 200g of OSA starch to 3000mL of deionized water at 50℃ and stir for 60 minutes to form a homogeneous colloidal solution.

[0034] (2) Adding core material Add 10g of vitamin B1, 15g of vitamin B2, 20g of vitamin B6, and 0.05g of vitamin B12 to the wall material solution in sequence. Stir well to avoid excessive local concentrations that could lead to degradation.

[0035] (3) Homogenization emulsification The mixture was processed using a high-pressure homogenizer at 100 MPa, with two cycles.

[0036] (4) Spray drying Equipment: Centrifugal spray drying tower, inlet air temperature: 150℃, feed rate: 15mL / min, after drying, free-flowing microcapsule powder is obtained.

[0037] (5) Cooling and collection The dried powder is collected by a cyclone separator and immediately cooled to room temperature. It is then sealed and stored in a desiccator, protected from light, to prevent moisture absorption.

[0038] Preparation method of creatine-complex B vitamin composition: Creatine monohydrate and silicified microcrystalline cellulose were premixed in a three-dimensional mixer at 20 rpm for 15 minutes. Add the complex B vitamin microcapsules and mix for 25 minutes at 20 rpm in a three-dimensional mixer at a temperature of 22°C and a relative humidity of 35%. Add magnesium stearate and mix for 10 minutes at 15 rpm in a three-dimensional mixer; A rotary tablet press is used, with a pressure of 40kN, producing tablets weighing 1.25g each, with a hardness of 60N.

[0039] Example 2 A creatine-based B-complex vitamin composition, comprising the following raw materials in parts by weight: Creatine monohydrate 65 parts, complex B vitamin microcapsules 4.2 parts, silicified microcrystalline cellulose 30 parts, magnesium stearate 0.8 parts.

[0040] Creatine monohydrate has a particle size of less than or equal to 80 mesh, a purity of 99.8%, and a D90 of approximately 90 μm. The siliconized microcrystalline cellulose is designated Prosolv SMCC 90, and the magnesium stearate has a particle size D90 of approximately 25 μm.

[0041] The preparation method of compound B vitamin microcapsules includes the following steps: (1) Wall materials are dispersed Add 200g of maltodextrin and 200g of OSA starch to 4000mL of deionized water at 60℃ and stir for 50 minutes to form a homogeneous colloidal solution.

[0042] (2) Adding core material Add 12g of vitamin B1, 20g of vitamin B2, 20g of vitamin B6, and 0.06g of vitamin B12 to the wall material solution in sequence. Stir well to avoid excessive local concentrations that could lead to degradation.

[0043] (3) Homogenization emulsification The mixture was processed using a high-pressure homogenizer at 80 MPa, with three cycles.

[0044] (4) Spray drying Equipment: Centrifugal spray drying tower, inlet air temperature: 160℃, feed rate: 20mL / min, after drying, free-flowing microcapsule powder is obtained.

[0045] (5) Cooling and collection The dried powder is collected by a cyclone separator and immediately cooled to room temperature. It is then sealed and stored in a desiccator, protected from light, to prevent moisture absorption.

[0046] Preparation method of creatine-complex B vitamin composition: Premix creatine monohydrate and silicified microcrystalline cellulose in a three-dimensional mixer at 30 rpm for 10 minutes. Add the complex B vitamin microcapsules and mix for 15 minutes at 25 rpm in a three-dimensional mixer at a temperature of 22°C and a relative humidity of 35%. Add magnesium stearate and mix for 5 minutes at 20 rpm in a three-dimensional mixer. A rotary tablet press is used, with a pressure of 30kN, producing tablets weighing 1.2g each with a hardness of 35N.

[0047] Example 3 A creatine-based B-complex vitamin composition, comprising the following raw materials in parts by weight: Creatine monohydrate 50 parts, complex B vitamin microcapsules 15 parts, silicified microcrystalline cellulose 34.5 parts, magnesium stearate 1.5 parts.

[0048] Creatine monohydrate has a particle size of less than or equal to 80 mesh, a purity of 99.8%, and a D90 of approximately 90 μm. The siliconized microcrystalline cellulose is designated Prosolv SMCC HD 90, and the magnesium stearate has a particle size D90 of approximately 25 μm.

[0049] The preparation method of compound B vitamin microcapsules includes the following steps: (1) Wall materials are dispersed Add 100g of maltodextrin and 300g of OSA starch to 4000mL of deionized water at 60℃ and stir for 50 minutes to form a homogeneous colloidal solution.

[0050] (2) Adding core material Add 12g of vitamin B1, 20g of vitamin B2, 60g of vitamin B6, and 0.1g of vitamin B12 to the wall material solution in sequence. Stir well to avoid excessive local concentrations that could lead to degradation.

[0051] (3) Homogenization emulsification The mixture was processed using a high-pressure homogenizer at 60 MPa, with three cycles.

[0052] (4) Spray drying Equipment: Centrifugal spray drying tower, inlet air temperature: 150℃, feed rate: 10mL / min, after drying, free-flowing microcapsule powder is obtained.

[0053] (5) Cooling and collection The dried powder is collected by a cyclone separator and immediately cooled to room temperature. It is then sealed and stored in a desiccator, protected from light, to prevent moisture absorption.

[0054] Preparation method of creatine-complex B vitamin composition: Premix creatine monohydrate and silicified microcrystalline cellulose in a three-dimensional mixer at 15 rpm for 20 minutes. Add the complex B vitamin microcapsules and mix for 15 minutes at 30 rpm in a three-dimensional mixer at a temperature of 22°C and a relative humidity of 35%. Add magnesium stearate and mix for 7 minutes at 20 rpm in a three-dimensional mixer. A rotary tablet press is used, with a pressure of 35kN, producing tablets weighing 1.2g each, with a hardness of 40N.

[0055] Example 4 A creatine-based B-complex vitamin composition, comprising the following raw materials in parts by weight: Creatine monohydrate 70 parts, complex B vitamin microcapsules 5 parts, silicified microcrystalline cellulose 24 parts, magnesium stearate 1 part.

[0056] Creatine monohydrate has a particle size of less than or equal to 80 mesh, a purity of 99.8%, and a D90 of approximately 90 μm. The siliconized microcrystalline cellulose is designated Prosolv SMCC 90LM, and the magnesium stearate has a particle size D90 of approximately 25 μm.

[0057] The preparation method of compound B vitamin microcapsules includes the following steps: (1) Wall materials are dispersed Add 100g of maltodextrin and 200g of OSA starch to 2800mL of deionized water at 60℃ and stir for 50 minutes to form a homogeneous colloidal solution.

[0058] (2) Adding core material Add 12g of vitamin B1, 20g of vitamin B2, 20g of vitamin B6, and 0.05g of vitamin B12 to the wall material solution in sequence. Stir well to avoid excessive local concentrations that could lead to degradation.

[0059] (3) Homogenization emulsification The mixture was processed using a high-pressure homogenizer at 80 MPa, with three cycles.

[0060] (4) Spray drying Equipment: Centrifugal spray drying tower, inlet air temperature: 160℃, feed rate: 20mL / min, after drying, free-flowing microcapsule powder is obtained.

[0061] (5) Cooling and collection The dried powder is collected by a cyclone separator and immediately cooled to room temperature. It is then sealed and stored in a desiccator, protected from light, to prevent moisture absorption.

[0062] Preparation method of creatine-complex B vitamin composition: Premix creatine monohydrate and silicified microcrystalline cellulose in a three-dimensional mixer at 30 rpm for 10 minutes. Add the complex B vitamin microcapsules and mix for 15 minutes at 25 rpm in a three-dimensional mixer at a temperature of 22°C and a relative humidity of 35%. Add magnesium stearate and mix for 5 minutes at 20 rpm in a three-dimensional mixer. A rotary tablet press is used, with a pressure of 30kN, producing tablets weighing 1.2g each with a hardness of 35N.

[0063] Example 5 A creatine-based B-complex vitamin composition, comprising the following raw materials in parts by weight: Creatine monohydrate 55 parts, complex B vitamin microcapsules 10 parts, silicified microcrystalline cellulose 34 parts, magnesium stearate 1 part.

[0064] Creatine monohydrate has a particle size of less than or equal to 80 mesh, a purity of 99.8%, and a D90 of approximately 90 μm. The siliconized microcrystalline cellulose is designated Prosolv SMCC 90LM, and the magnesium stearate has a particle size D90 of approximately 25 μm.

[0065] The preparation method of compound B vitamin microcapsules includes the following steps: (1) Wall materials are dispersed Add 200g of maltodextrin and 200g of OSA starch to 3800mL of deionized water at 60℃ and stir for 50 minutes to form a homogeneous colloidal solution.

[0066] (2) Adding core material Add 12g of vitamin B1, 20g of vitamin B2, 20g of vitamin B6, and 0.06g of vitamin B12 to the wall material solution in sequence. Stir well to avoid excessive local concentrations that could lead to degradation.

[0067] (3) Homogenization emulsification The mixture was processed using a high-pressure homogenizer at 80 MPa, with three cycles.

[0068] (4) Spray drying Equipment: Centrifugal spray drying tower, inlet air temperature: 160℃, feed rate: 20mL / min, after drying, free-flowing microcapsule powder is obtained.

[0069] (5) Cooling and collection The dried powder is collected by a cyclone separator and immediately cooled to room temperature. It is then sealed and stored in a desiccator, protected from light, to prevent moisture absorption.

[0070] Preparation method of creatine-complex B vitamin composition: Premix creatine monohydrate and silicified microcrystalline cellulose in a three-dimensional mixer at 30 rpm for 10 minutes. Add the complex B vitamin microcapsules and mix for 15 minutes at 25 rpm in a three-dimensional mixer at a temperature of 22°C and a relative humidity of 35%. Add magnesium stearate and mix for 5 minutes at 20 rpm in a three-dimensional mixer. A rotary tablet press is used, with a pressure of 30kN, producing tablets weighing 1.2g each with a hardness of 35N.

[0071] Comparative Example 1 A creatine-based B-complex vitamin composition, with the raw material composition as described in Example 1, except that it uses unencapsulated B-complex vitamins; specifically, it consists of the following raw materials in parts by weight: Creatine monohydrate 60 parts, vitamin B complex 7 parts (B1:B2:B6:B12 mass ratio of 1:1.5:2.0:0.005), silicified microcrystalline cellulose 32 parts, magnesium stearate 1 part.

[0072] Other raw material types and parameters are the same as in Example 1.

[0073] Preparation method of creatine-complex B vitamin composition: Creatine monohydrate and silicified microcrystalline cellulose were premixed in a three-dimensional mixer at 20 rpm for 15 minutes. Add B vitamins and mix for 25 minutes at 20 rpm in a three-dimensional mixer at a temperature of 22°C and a relative humidity of 35%. Add magnesium stearate and mix for 10 minutes at 15 rpm in a three-dimensional mixer; A rotary tablet press is used, with a pressure of 40kN, producing tablets weighing 1.25g each, with a hardness of 60N.

[0074] Comparative Example 2 A creatine-based B-complex vitamin composition, with the raw material composition as described in Example 1, except that it uses unencapsulated B-complex vitamins; specifically, it consists of the following raw materials in parts by weight: Creatine monohydrate 60 parts, B vitamins 7 parts (B1:B2:B6:B12 ratio 1:1.5:2.0:0.005), silicified microcrystalline cellulose 32 parts, magnesium stearate 1 part.

[0075] Other raw material types and parameters are the same as in Example 1.

[0076] The wet granulation process is adopted, and the specific method is as follows: Creatine monohydrate and silicified microcrystalline cellulose were premixed in a wet granulator at 200 rpm for 5 minutes. Add B vitamins and premix for 10 minutes at 200 rpm in a wet granulator at 22°C and 35% relative humidity; add deionized water to make a soft mass, and then pass it through a 30-mesh sieve to make wet granules.

[0077] Dry in an oven at 50℃.

[0078] Add magnesium stearate and mix for 10 minutes at 15 rpm in a three-dimensional mixer; A rotary tablet press is used, with a pressure of 40kN, producing tablets weighing 1.25g each, with a hardness of 60N.

[0079] Comparative Example 3: Changing the wall material ratio (OSA starch: maltodextrin = 1:2) A creatine-based B vitamin composition, with the raw material composition as described in Example 1, except that the wall material for microcapsule preparation is 100g OSA starch + 200g maltodextrin.

[0080] The other steps and conditions are the same as in Example 1.

[0081] Comparative Example 4: Wall material using only maltodextrin A creatine-based B vitamin composition, with the raw material composition as described in Example 1, except that the wall material for the microcapsule preparation is only 300g of maltodextrin, without OSA starch.

[0082] The other steps and conditions are the same as in Example 1.

[0083] Comparative Example 5 A creatine-based B vitamin composition, with the raw material composition as described in Example 1, except that: silicified microcrystalline cellulose (Prosolv SMCC 90 LM) is replaced with an equal amount of ordinary microcrystalline cellulose (MCC 102).

[0084] The other steps and conditions are the same as in Example 1.

[0085] Comparative Example 6: B vitamins without VB2 A creatine-based B-complex vitamin composition, with the raw material composition as described in Example 1, except that vitamin B2 is not added to the B-complex vitamin microcapsules.

[0086] The other steps and conditions are the same as in Example 1.

[0087] Test Example 1: Tablet Friability Test The friability of Examples 1-5 and Comparative Examples 1-2 was tested according to the tablet friability test method provided in the Chinese Pharmacopoeia (2025 Edition, Part IV, 0923). Tablet friability is a physical property indicator reflecting the tablet's resistance to abrasion and vibration, used to assess whether tablets are easily broken or worn during production, transportation, and storage. The test method usually involves placing a certain number of tablets in a friability tester, subjecting them to rotational friction for a specified time, and calculating the friability by weighing the weight loss of the tablets. Generally, the weight loss should not exceed 1%.

[0088] Take 5-6 flakes from each group, blow off the powder from the flakes with a hair dryer, weigh them precisely using an electronic balance, and record the weight as the pre-test weight. Place the flakes in the cylinder of a friability tester and rotate them 100 times. Remove them, remove the powder using the same method, weigh them precisely, and record the weight as the post-test weight. Calculate the loss rate.

[0089] Loss rate = (Weight before testing - Weight after testing) ÷ Weight before testing × 100%. The higher the loss rate, the more easily the tablets crumble into powder.

[0090] The loss rate results are summarized in Table 1.

[0091] Table 1. Results of tablet friability test As shown in Table 1, the friability of Examples 1-5 and Comparative Examples 1-2 all met the requirements, but the friability loss rates of Comparative Examples 1 and 2 were slightly higher than those of Examples 1-5. The friability loss rates of Comparative Examples 3-6 were also higher than those of Examples 1-5, especially Comparative Example 4 (using only maltodextrin as the wall material) and Comparative Example 5 (replacing silicified microcrystalline cellulose with ordinary microcrystalline cellulose), where the loss rates increased significantly, reaching 0.257% and 0.289%, respectively. This indicates that the microcapsule wall material ratio and excipient selection have a significant impact on tablet friability, and the composite wall material and silicified microcrystalline cellulose used in the examples can effectively reduce friability. The loss rate of Comparative Example 6 (without VB2) was 0.167%, slightly higher than the examples but lower than the other comparative examples, indicating that the absence of VB2 has a relatively small impact on friability. Overall, the tablets of Examples 1-5 exhibited the best friability performance, meeting pharmacopoeia requirements and having the lowest loss rate.

[0092] Experimental Example 2: Content Uniformity and Dissolution Test Methods: The content uniformity determination was performed according to the method specified in the Chinese Pharmacopoeia (2025 edition, Part IV, 0941). Ten tablets each from Examples 1-5 and Comparative Examples 1-6 were ground finely in a mortar. An appropriate amount (approximately equivalent to the average tablet weight) was accurately weighed and placed in a 100 mL volumetric flask. An appropriate amount of mobile phase was added, and the mixture was sonicated to dissolve. After cooling, the solution was diluted to the mark with the mobile phase, shaken well, and filtered. The filtrate was used as the test solution. Separately, appropriate amounts of creatine and B vitamin reference standards were accurately weighed and mixed with the mobile phase to prepare a mixed reference solution containing approximately a certain amount of creatine and each B vitamin per mL. The test solution and the mixed reference solution were analyzed by high-performance liquid chromatography (HPLC). The content of creatine and each B vitamin in each tablet was calculated, and the content uniformity (based on a relative content of 100% of the labeled amount) was calculated. Generally, the content per tablet should be between 85% and 115% of the labeled amount.

[0093] Dissolution was determined using the paddle method with 900 mL of 0.1 mol / L hydrochloric acid aqueous solution as the dissolution medium and a rotation speed of 50 rpm. After 30 minutes, an appropriate amount of solution was taken, filtered, and the filtrate was used as the test solution.

[0094] Separately weigh appropriate amounts of creatine and each B vitamin reference standard, and add dissolution medium to prepare a mixed reference solution containing approximately a certain amount of creatine and each B vitamin per 1 mL. Take the test solution and the mixed reference solution, and determine them using high performance liquid chromatography (HPLC). Calculate the amount of creatine and each B vitamin dissolved in each tablet within the specified time, and calculate the dissolution rate (relative dissolution rate with the labeled amount as 100). Generally, the dissolution rate should not be less than 75% of the labeled amount after 30 minutes.

[0095] Table 2 Results of content uniformity and dissolution rate Table 2 shows that the content uniformity of Examples 1-5 was between 85% and 115% of the labeled amount, meeting the pharmacopoeia requirements, and the dissolution rate was not less than 75% of the labeled amount, indicating that creatine and various B vitamins were evenly distributed in the tablets and could be effectively dissolved within the specified time. Although the content uniformity of Comparative Examples 1-6 was also basically within the specified range, their dissolution rates were significantly lower than those of the Examples, especially Comparative Example 3 (OSA starch: maltodextrin = 1:2), Comparative Example 4 (wall material only maltodextrin), and Comparative Example 5 (replacing siliconized microcrystalline cellulose with ordinary microcrystalline cellulose), whose dissolution rates dropped to 83%, 78%, and 81%, respectively, indicating that the wall material ratio and excipient selection have an important impact on dissolution rate. The dissolution rate of Comparative Example 6 (without VB2) was 84%, which was slightly higher than the other comparative examples but lower than that of the Examples, indicating that the absence of VB2 had a certain impact on dissolution rate. Overall, Examples 1-5 showed the best performance in terms of content uniformity and dissolution, meeting pharmacopoeia requirements and exhibiting the best dissolution effect.

[0096] Further analysis of the data in Table 2 reveals that while there were some fluctuations between Examples 1 to 5, the overall content uniformity and dissolution data remained relatively stable, reflecting the reliability and consistency of the preparation process. Example 5, in particular, demonstrated outstanding performance in dissolution, achieving a creatine dissolution rate of 97%, which may be related to the optimization of raw material ratios and preparation process parameters in this example. In contrast, Comparative Examples 1 to 6 showed varying degrees of decrease in both content uniformity and dissolution, especially Comparative Examples 4 and 5, where the dissolution rate significantly decreased due to the selection of wall materials and excipient substitutions. This further verifies the significant impact of wall material ratios and excipient selection on product performance. Although riboflavin (VB2) was removed in Comparative Example 6, its impact on overall content uniformity and dissolution was relatively small, indicating that riboflavin plays a relatively limited role in the overall performance of the tablets; however, this would result in a loss of nutrients. In summary, Examples 1 to 5 performed excellently in terms of content uniformity and dissolution, meeting pharmacopoeia requirements, and the preparation process was stable and reliable.

[0097] Test Example 3: Product Stability Test According to the "Technical Regulations for the Evaluation of Health Foods", the creatine complex B vitamin composition obtained in Examples 1 to 5 was placed at 37-40°C and 75% humidity. Indicators that can represent the intrinsic quality of the product, such as total bacterial count, yeast, and mold, were selected and sampled and measured once a month for three consecutive months. If the measured indicators were stable, it was equivalent to being able to be stored for two years.

[0098] Accelerated testing (40℃±2℃, RH 75%±5%) was conducted on samples from the examples and comparative samples at 0, 1, 2, 3, and 6 months. Content analysis was performed according to the National Food Safety Standard for Sports Nutrition Foods (GB 24154-2015) and its relevant revisions, using creatine, vitamins B1, B2, B6, and B12 as indicator components, and calculating their content retention rates. A higher content retention rate indicates better product stability under those conditions. The results are shown in Table 3.

[0099] Table 3 Results after six months of accelerated testing As shown in Table 3, the accelerated stability test results of Examples 1 to 5 indicate that the retention rates of all indicators remained at a high level after six months. The retention rates of creatine and various B vitamins were generally higher than 85%, and the product appearance did not show significant changes, indicating that the products possess good stability and compatibility under these accelerated conditions. Among them, Examples 1 and 3 showed relatively high vitamin retention rates, with creatine retention rates reaching 93%, demonstrating superior stability.

[0100] In comparison, the stability of Comparative Examples 1 to 6 was significantly reduced. Not only did the vitamin retention rate decline drastically, but some samples also exhibited changes in appearance, such as yellowing, moisture absorption, and wear. Comparative Examples 3 and 4, in particular, showed more severe moisture absorption due to differences in wall material ratios and excipient selection, further impacting their stability and compatibility. Although Comparative Example 6 did not show any changes in appearance, its vitamin retention rates were lower than those of the examples and other comparative examples, indicating that the absence of VB2 may have had some impact on the overall product stability.

[0101] Experimental Example 4: Evaluation of Exercise Effects Sixty healthy adult males (age 26.6±2.3 years; height 174.1±6.2 cm; weight 76.5±6.3 kg) were randomly divided into 3 groups. Group A: Take the product of Example 1, 1 tablet twice daily; Group B: Administered a single creatine preparation (5g / day); Group C: Placebo (starch tablets, 1.25g / tablet, 1 tablet twice daily).

[0102] Before the experiment began, all subjects underwent basic physical fitness tests, including 1RM bench press and squat repetitions, as well as muscle mass and fatigue recovery time measurements.

[0103] The experiment lasted for 8 weeks. During the experiment, participants maintained their original daily diet and exercise habits (those with regular exercise habits continued to do so; those without did not receive any additional exercise intervention). After the 8th week of the experiment, participants underwent the same physical fitness and performance indicators tests. Data were recorded, and changes in 1RM bench press, squat repetitions, muscle mass, and recovery time were calculated compared to before the experiment. The test results are shown in Table 4.

[0104] Table 4. Improvement in athletic performance (n=20, x±s) Note: * P < 0.05 compared to group C, # P < 0.05 compared to group B The results showed that after an 8-week experimental period, Group A (taking the product of Example 1) significantly outperformed Group B (taking creatine alone) and Group C (placebo) in all physical fitness tests. Specifically, Group A increased its 1RM bench press strength by 12.3 ± 2.1 kg, squat repetitions by 28.5 ± 4.3, and muscle mass by 2.8 ± 0.5 kg, while its recovery time decreased by 1.5 ± 0.3 hours. These improvements were statistically significant compared to Group C (P < 0.05). Compared to Group B, Group A also showed more significant improvements in strength, squat repetitions, muscle mass, and recovery time (P < 0.05).

[0105] While Group B also showed some improvement in physical fitness, the increase was smaller compared to Group A. For example, Group B's strength in the 1RM bench press increased by 8.7±1.9 kg, squat repetitions increased by 19.6±3.8, muscle mass increased by 1.9±0.4 kg, and recovery time decreased by 0.8±0.2 hours. These data indicate that while creatine alone can help improve physical fitness, its effect is not as good as the compound preparation in Example 1.

[0106] Group C, as the placebo group, showed little change in its physical fitness test data before and after the experiment, with no significant improvement in any of the indicators (P > 0.05). This further validated the effectiveness of the experimental design and the reliability of the results.

[0107] In summary, the creatine-B vitamin combination of Example 1 performed exceptionally well in enhancing strength, endurance, muscle mass, and accelerating fatigue recovery, significantly outperforming single creatine formulations and placebos, indicating that this combination formulation has broad application prospects in the field of sports nutrition.

[0108] Experimental Example 5 Bioavailability Bioavailability is an important indicator for evaluating the absorption and utilization of drugs or nutritional supplements in the body. To assess the bioavailability of the creatine and B vitamin combination of Example 1, the following experiment was conducted. Thirty Wistar rats (weighing 200±20g) were randomly divided into three groups of 10 each. Group A: administered the product of Example 1 by gavage (converted to 50mg / kg based on creatine content); Group B: administered creatine alone by gavage (50mg / kg); Group C: administered an equal volume of physiological saline as a control by gavage. At 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after administration, 0.5mL of blood was collected from the retro-orbital venous plexus of the rats, placed in heparin anticoagulant tubes, and the plasma was separated by centrifugation. The concentrations of creatine and each B vitamin in the plasma were determined by high-performance liquid chromatography (HPLC). The area under the plasma concentration-time curve (AUC) was used as the evaluation index for bioavailability. The determination method used was HPLC with a diode array detector (DAD) and a fluorescence detector (FLD), as detailed below: Chromatographic column: C18 reversed-phase column, 250 mm × 4.6 mm, 5 μm (Agilent Zorbax SB-C18).

[0109] Mobile phase: Phase A: 20 mM potassium dihydrogen phosphate + 5 mM sodium heptanesulfonate (ion-pairing reagent). Adjust pH to 3.0 ± 0.1 with phosphoric acid. Filter and sonicate to degas; Phase B: acetonitrile; Flow rate: 1.0 mL / min, column temperature: 30℃, injection volume: 20 μL.

[0110] Gradient procedure: Detector conditions: DAD: Creatine: 210 nm; Vitamin B1: 254 nm; Vitamin B12: 361 nm; simultaneous multi-wavelength monitoring. FLD (in series after DAD): Vitamin B2: Ex: 440 nm / Em: 520 nm; Vitamin B6: Ex: 290 nm / Em: 395 nm Table 5: Mean pharmacokinetic parameters of creatine in rat plasma in each group (n=10, X±SD) Table 6: Mean AUC of B vitamins in the plasma of rats in each group 0-24 (n=10, X ± SD) Calculation of relative bioavailability of creatine: Using group B as a reference, the relative bioavailability of group A... F=(AUCA / AUCB)×100%=(125.5 / 85.2)×100%≈147.3% Interpretation of creatine results: Higher absorption: AUC of Group A (combination tablets) 0-24 and C max Both were significantly higher than those in group B, indicating that the total amount of creatine absorbed and the maximum blood concentration were superior to those of creatine alone.

[0111] Absorption rate and sustained-release characteristics: Group A's T max Significantly greater than group B, combined with its longer half-life (t 1 / 2 This strongly suggests that the compound tablet may have a sustained-release effect. It allows for a smoother and more sustained release and absorption of creatine, avoiding the "peak-valley effect" of creatine alone.

[0112] Bioavailability: A relative bioavailability of 156.1% clearly demonstrates that the combination tablets significantly improve the utilization efficiency of creatine in vivo compared to creatine alone.

[0113] Interpretation of B vitamin results: Effective delivery: The AUC values ​​of all B vitamins in Group A were at a high level, proving that the B vitamins in the tablets were effectively released and absorbed into the bloodstream.

[0114] No synergistic absorption: The AUC values ​​of each vitamin in group B (creatine alone) were not significantly different from those in group C (blank control), indicating that creatine supplementation alone does not increase the baseline levels of B vitamins in the body. This contradicts the fact that the increase in blood vitamin levels in group A is entirely due to its combination tablets.

[0115] Specificity of Vitamin B12: Since Vitamin B12 is mainly found in animal foods and at extremely low physiological levels, no obvious pharmacokinetic signals were detected in the plasma of groups B and C, while group A showed a clear B12 absorption peak, proving the effectiveness of its supplementation.

[0116] In summary, Examples 1 to 5 demonstrated excellent performance in accelerated stability testing, validating the rationality of their preparation process and the reliability of their product quality. In the exercise effect evaluation test, the compound formulation of Example 1 exhibited significant advantages, further highlighting its practical application value. The bioavailability test results provided solid support for the product's efficacy from a pharmacokinetic perspective. The compound tablets not only significantly improved the total absorption, maximum plasma concentration, and bioavailability of creatine, but also achieved effective delivery of B vitamins, avoiding the situation where creatine supplementation alone had no effect on B vitamin absorption, while ensuring the effective supplementation of special nutrients such as vitamin B12. These test results collectively indicate that this creatine-B vitamin combination exhibits excellent performance in terms of preparation process, product quality stability, and bioavailability, possessing extremely high market application potential and promotional value.

Claims

1. A creatine-complex B-vitamin composition, characterized in that, It is composed of the following raw materials in parts by weight: 50-70 parts creatine monohydrate, 4-20 parts complex B vitamin microcapsules, 15-40 parts silicified microcrystalline cellulose (SMCC), and 0.5-1.5 parts magnesium stearate.

2. The creatine-complex B vitamin composition according to claim 1, characterized in that, The creatine complex B vitamin composition comprises the following raw materials in parts by weight: 50-70 parts creatine monohydrate, 4.2-15 parts complex B vitamin microcapsules, 24-34.5 parts silicified microcrystalline cellulose (SMCC), and 0.8-1.5 parts magnesium stearate.

3. The creatine-complex B-vitamin composition according to claim 1, characterized in that, The compound B vitamin microcapsules contain compound vitamins B1, B2, B6, and B12.

4. The creatine-complex B vitamin composition according to claim 1, characterized in that, The preparation method of compound B vitamin microcapsules includes the following steps: Octyl succinate-modified starch and maltodextrin are fully dissolved in water, and vitamins B1, B2, B6, and B12 or a mixture of vitamins B1, B2, B6, and B12 are added and mixed thoroughly. Then, the mixture is homogenized, emulsified, and spray-dried to obtain complex B vitamin microcapsules.

5. The creatine-complex B vitamin composition according to claim 4, characterized in that, The mass ratio of octenyl succinate starch to maltodextrin is 1~3:1; the mass ratio of octenyl succinate starch to water is 1:13.3~20.

6. The creatine-complex B-vitamin composition according to claim 4, characterized in that, Includes one or more of the following conditions: i. Add octyl succinate starch and maltodextrin to water and stir at 50–60°C for 30–60 minutes; ii. The mass ratio of vitamin B1, vitamin B2, vitamin B6, and vitamin B12 is (1.0-2.0):(1.0-2.0):(1.5-5.0):(0.002-0.02), preferably 1:1.50-1.67:1.67-5.0:0.0042-0.0083; iii. The total mass ratio of vitamin B1, vitamin B2, vitamin B6, and vitamin B12 to octyl succinate starch is 22-31:100; iv. Homogenization emulsification conditions: homogenize 2–3 times at 50–100 MPa; v. Spray drying conditions are as follows: inlet air temperature: 150–170℃, feed rate: 10–20 mL / min.

7. The creatine-complex B-vitamin composition according to claim 1, characterized in that, The siliconized microcrystalline cellulose (SMCC) is of at least one of Prosolv SMCC 90, Prosolv SMCC 90 LM or Prosolv SMCC HD 90; preferably, the siliconized microcrystalline cellulose (SMCC) is of the type Prosolv SMCC 90 LM.

8. The creatine-complex B-vitamin composition according to claim 1, characterized in that, The particle size D90 of magnesium stearate is 10-30 μm, more preferably 12-25 μm, and most preferably 25 μm.

9. A method for preparing the creatine complex B vitamin composition according to any one of claims 1-8, comprising the steps of: Creatine monohydrate and silicified microcrystalline cellulose (SMCC) are premixed; compound B vitamin microcapsules are added and mixed evenly; magnesium stearate is added and mixed thoroughly; then the mixture is compressed into tablets to obtain a creatine compound B vitamin composition.

10. The method for preparing the creatine complex B vitamin composition according to claim 9, characterized in that, Includes one or more of the following conditions: i. The premixing time is 10-20 minutes, and the premixing speed is 15-30 rpm; ii. After adding the compound B vitamin microcapsules, mix at 15-25 rpm for 10-30 minutes in an environment with a relative humidity ≤40% and a mixing temperature of 20-25℃ to ensure uniform mixing; preferably, the relative humidity is 20-40%. iii. After adding magnesium stearate, mix at 15-20 rpm for 5-10 minutes; iv. The tableting pressure is 30-50kN, the tablet weight is controlled at 1.0-1.3g, and the hardness is controlled at 30-80N.

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