Preparation method of ultramicro creatine flash-soluble composition, composition and application

Abstract

The invention relates to the technical field of functional food, in particular to a preparation method of an ultramicro creatine flash-soluble composition, the composition and application. The method comprises the following steps: crushing creatine monohydrate and carrying out static elimination treatment to obtain superfine creatine; zinc glycinate and magnesium glycinate are mixed, spray coating is performed to form microcapsules, and the zinc-magnesium amino acid chelate is obtained; carrying out dry mixing on the superfine creatine and the zinc-magnesium amino acid chelate, spraying a mixed solution of sodium alginate and fruit powder, and carrying out freeze drying to form a porous embedding structure, so as to obtain the superfine creatine zinc-magnesium compound; and uniformly mixing the embedded superfine creatine zinc-magnesium compound with erythritol and xylitol, and carrying out ultraviolet sterilization to obtain the superfine creatine flash-soluble composition. The bioavailability of creatine is effectively improved, and the generation of creatinine is reduced, so that the liver and kidney metabolism burden is reduced. Meanwhile, the addition amount and the existence form of the magnesium element are reasonably controlled, the diarrhea problem caused by large dosage of magnesium is avoided, and the safety and the effectiveness of the sports nutritional supplement are improved.

Description

Technical Field

[0001] The present invention relates to the technical field of functional foods, and particularly relates to a preparation method, a composition, and an application of an ultramicro creatine instant dissolution composition. Background Art

[0002] In the field of sports nutrition supplements, creatine, as a widely used nutritional component, has significant effects on improving muscle strength, increasing muscle mass, and enhancing exercise endurance, and thus is favored by athletes and fitness enthusiasts.

[0003] However, the stability of creatine in the human digestive system affects the use effect and safety of creatine. The environment in the human stomach is acidic, and the pH value of gastric acid is approximately between 1.5 and 3.5. Under such acidic conditions, creatine will undergo a partial hydrolysis reaction and be converted into creatinine. The generation of creatinine brings two adverse effects. On the one hand, the hydrolysis of creatine leads to a decrease in its bioavailability. Since part of the creatine is converted into creatinine in the stomach, the amount of creatine that can be effectively absorbed and utilized by the human body decreases, which means that in order to achieve the expected supplementation effect, users need to ingest a higher dose of creatine. On the other hand, the creatinine produced in the stomach will increase the metabolic burden on the liver and kidneys. The liver and kidneys are important metabolic and excretory organs of the human body, and the additional creatinine needs to be processed and excreted by the liver and kidneys. If this continues for a long time, it may have an adverse effect on the normal functions of the liver and kidneys and even cause related health problems.

[0004] To make up for the loss of creatine in the stomach, the prior art, such as Chinese Patent Publication No. CN101331949B, adopts a strategy of supplementing according to a high proportion of creatine content. This method attempts to ensure that after a part of the surplus creatine is consumed in the stomach, there is still enough amount to reach the small intestine for metabolism. Although it ensures the amount of creatine reaching the small intestine to a certain extent, it does not solve the fundamental problems of creatine hydrolysis in the stomach and the increase in the burden on the liver and kidneys caused by creatinine. Summary of the Invention

[0005] In view of the technical problem in the prior art that according to a high proportion of creatine content, creatine reaches the small intestine for metabolism when the surplus is consumed in the stomach, but the creatinine produced in the stomach will increase the metabolic burden on the liver and kidneys.

[0006] The first aspect of the present application mentions a preparation method of an ultramicro creatine instant dissolution composition, including: Crushing monohydrate creatine to ≥500 mesh and performing electrostatic elimination treatment to obtain ultramicro creatine; Mixing zinc glycinate and magnesium diglycinate in a molar ratio of Zn:Mg of 1:(2 - 3) and spray coating to form microcapsules to obtain zinc-magnesium amino acid chelate; Dry mix ultramicronized creatine with zinc magnesium amino acid chelate, spray it into the mixed solution of sodium alginate and fruit powder, and freeze-dry to form a porous embedding structure to obtain an ultramicronized creatine zinc magnesium complex; Mix the embedded ultramicronized creatine zinc magnesium complex with erythritol and xylitol, and perform ultraviolet sterilization to obtain an ultramicronized creatine instant dissolving composition.

[0007] Further, add the mixture of zinc glycinate and magnesium diglycinate into a fluidized bed coating device, with an atomizing pressure of 0.4 - 0.6 MPa and an inlet air temperature of 120 - 140 °C; In the mixed solution of sodium alginate and fruit powder, the concentration of sodium alginate is 1.5 - 2.5% w / v, and the content of fruit powder is 3 - 8% w / v; the spraying rate during spraying is controlled at 5 - 10 wt% / min of the total weight of the mixed materials.

[0008] Further, before freeze-drying, add sodium bicarbonate with a mass fraction of 0.5% - 1% to the mixed solution for releasing gas during the freezing process.

[0009] Further, gradient cooling is adopted for freeze-drying. First, cool down to below -40 °C at a rate of 10 - 15 °C / min and keep it for 1 - 2 hours for thorough freezing; then heat up to -15 - 20 °C at a rate of 0.8 - 1.2 °C / min and keep it for 1 hour; then heat up to -5 - 0 °C at a rate of 1.0 - 1.5 °C / min and keep it for 0.5 hour; finally, under a vacuum degree of <10 Pa, heat up to 30 - 40 °C at a rate of 1.5 - 2.5 °C / min and keep it for 1 - 2 hours until completely dry.

[0010] Further, the mass ratio of erythritol to xylitol is (1 - 3):1, and the total mass of the two accounts for 60 - 80% of the total mass of the ultramicronized creatine instant dissolving composition.

[0011] Further, before ultraviolet sterilization, perform hot air activation treatment at 30 - 45 °C for 20 minutes, and select the double-band alternating irradiation of 200 - 265 nm and 150 - 185 nm for the ultraviolet wavelength.

[0012] Further, after ultraviolet sterilization, place the composition in an environment with a humidity ≤ 10%RH and a temperature ≤ 10 °C to cool and stand for 24 - 48 hours, and perform vacuum dehumidification packaging.

[0013] The second aspect of this application mentions an ultramicronized creatine instant dissolving composition, which is prepared by using the preparation method of an ultramicronized creatine instant dissolving composition mentioned in the first aspect. By weight percentage, it includes: Ultra - fine creatine: 40% - 50%, erythritol: 30% - 40%, xylitol: 5% - 10%, fruit powder: 5% - 10%, zinc amino acid chelate calculated as zinc ion: 0.5% - 5%, magnesium amino acid chelate calculated as magnesium ion: 1% - 10%.

[0014] Furthermore, the fruit powder is blueberry powder or blackcurrant powder and is subjected to freeze - drying treatment.

[0015] The third aspect of the present application mentions the application of the ultra - fine creatine instant - dissolving composition in the preparation of sports nutrition supplements, and the supplements are instant - dissolving powder, sports drink or solid capsule.

[0016] The beneficial effects of the present application are as follows: The present invention relates to the technical field of functional foods, and in particular to a preparation method, a composition and an application of an ultra - fine creatine instant - dissolving composition. Among them, the method includes: crushing monohydrate creatine and performing electrostatic elimination treatment to obtain ultra - fine creatine; mixing zinc glycinate and magnesium diglycinate and spray - coating to form microcapsules to obtain zinc - magnesium amino acid chelate; dry - mixing the ultra - fine creatine and the zinc - magnesium amino acid chelate, spraying into a mixed solution of sodium alginate and fruit powder, and freeze - drying to form a porous embedding structure to obtain an ultra - fine creatine zinc - magnesium complex; mixing the embedded ultra - fine creatine zinc - magnesium complex with erythritol and xylitol, and performing ultraviolet sterilization to obtain the ultra - fine creatine instant - dissolving composition.

[0017] In the gastric stage of the present application, by using hydroxypropyl methylcellulose enteric - coating and freeze - drying, the enteric - coating can effectively resist the strong acid erosion of gastric acid, and the microporous network formed by the sodium alginate gel through pore - forming with sodium bicarbonate can delay the penetration of hydrogen ions and significantly inhibit the hydrolysis reaction of creatine in gastric acid. Entering the intestinal absorption stage, with the help of the carrier function of the zinc - magnesium amino acid chelate, by adjusting the ratio of zinc and magnesium elements, active ion transmembrane transport is achieved. Combining with the fast - dissolving characteristic of ultra - fine creatine, the ultra - fine creatine particles are instantaneously released in the porous gel network, and trace zinc and magnesium ions efficiently capture creatine molecules through the slow - release guiding peptide transporter, achieving two - component co - transport. It avoids the generation of creatinine due to ineffective hydrolysis and reduces the kidney clearance burden. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to make the content of the present invention easier to be clearly understood, the following further details the present invention according to the specific embodiments of the present invention and in combination with the drawings.

[0019] Figure 1 It is a process flow chart of a preparation method of a novel ultra - fine creatine composition mentioned in the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0020] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the examples given are not intended to limit the present invention.

[0021] It should be noted that, in addition to the problem of creatine hydrolysis, the addition of magnesium in sports nutrition supplements also has potential risks. Magnesium plays an important role in physiological processes such as human metabolism, nerve conduction, and muscle contraction. Appropriate addition of magnesium in sports nutrition supplements helps improve sports performance and promote recovery. However, high doses of magnesium can cause adverse reactions such as diarrhea. This not only affects the absorption of nutrients by the human body but also brings physical discomfort to users, reducing the user experience and compliance of the product.

[0022] In view of these problems existing in the prior art, the present application mentions a preparation method for a novel ultramicro creatine composition. By improving the preparation process, the problem of creatine hydrolysis in an acidic environment can be effectively solved, the bioavailability of creatine can be improved, the production of creatinine can be reduced, and thus the metabolic burden on the liver and kidneys can be reduced. At the same time, the addition amount and existing form of magnesium are reasonably controlled to avoid diarrhea caused by high doses of magnesium, and the safety and effectiveness of sports nutrition supplements are improved. It is expected to provide better and safer nutrition supplement options for athletes and fitness enthusiasts and promote the development of the sports nutrition field.

[0023] For this purpose, referring to Figure 1 , the first aspect of the present application mentions a preparation method for an ultramicro creatine instant-soluble composition, including: Step S1: Crush monohydrate creatine to ≥500 mesh, D90 ≤ 15 μm, and treat it with an ion air gun at a wind speed of 2 - 3 m / s for electrostatic elimination treatment to obtain ultramicro creatine; It should be noted that crushing to a fineness of more than 500 mesh increases the specific surface area, providing a structural basis for subsequent encapsulation; the crushing of monohydrate creatine is carried out using a low-temperature nitrogen gas jet mill, with a crushing temperature of -10°C to -5°C and a crushing pressure of 1.0 - 1.2 MPa. Using low-temperature nitrogen gas jet milling effectively avoids the thermal degradation of creatine and maintains the integrity of the molecular structure.

[0024] After eliminating surface static electricity, the particle aggregation rate is reduced, which can improve the subsequent mixing uniformity.

[0025] Step S2: Mix zinc glycinate and magnesium diglycinate at a molar ratio of Zn:Mg of 1:(2 - 3), and spray-coat to form microcapsules to obtain a zinc-magnesium amino acid chelate with a particle size of 20 - 50 μm; the spray-coating is carried out using a fluidized bed spray coater, the coating is hydroxypropyl methylcellulose, and the mass ratio of the coating material to the core material is 1:5 - 1:8. The inlet air temperature is 50 - 60°C, which is used to protect the zinc-magnesium chelate from degradation by gastric acid, slowly release it for intestinal absorption, and avoid direct contact between metal ions and creatine, which may cause oxidation.

[0026] It should be noted that the molar ratio of Zn:Mg is 1:2, simulating the ion channel ratio for intestinal absorption to promote co-absorption. Hydroxypropyl methylcellulose is used as an enteric coating and is insoluble in the gastric acid environment (pH 1 - 3) to avoid creatine oxidation caused by the release of metal ions; it is slowly released in the intestinal alkaline environment (pH > 5.5), further improving the bioavailability.

[0027] Step S3: Dry-mix ultramicro creatine with zinc-magnesium amino acid chelate, spray it into a mixed solution of sodium alginate and fruit powder with a solid content of 5%, and freeze-dry to form a porous embedding structure to obtain an ultramicro creatine zinc-magnesium complex. In the mixed solution of sodium alginate and fruit powder, the concentration of sodium alginate is 1.5 - 2.5% w / v, and the content of fruit powder is 3 - 8% w / v; the spraying rate during spraying is controlled at 5 - 10 wt% / min of the total weight of the mixed materials.

[0028] Among them, a GLATT GPCG2 fluidized bed is used to control the spraying rate of the sodium-fruit powder solution at 5 - 8 mL / min.

[0029] In the porous embedding system of the micro-creatine zinc-magnesium complex, the core materials are micro-creatine and zinc-magnesium amino acid chelate, the coating material is sodium alginate, and a porous network is formed by low-temperature gelation. The fruit powder acts as an antioxidant and flavoring agent.

[0030] In this technical solution, before freeze-drying, sodium bicarbonate with a mass fraction of 0.5% - 1% is added to the mixed solution for release during the freezing process. Gas.

[0031] In this technical solution, gradient cooling is used for freeze-drying. First, cool down to below -40°C at a rate of 10 - 15°C / min and hold for 1 - 2 hours for thorough freezing; then warm up to -15 - 20°C at a rate of 0.8 - 1.2°C / min and hold for 1 hour; then warm up to -5 - 0°C at a rate of 1.0 - 1.5°C / min and hold for 0.5 hour; finally, under a vacuum of <10 Pa, warm up to 30 - 40°C at a rate of 1.5 - 2.5°C / min and keep warm for 1 - 2 hours until completely dry. After the sodium alginate and fruit powder composite solution is freeze-dried, a network structure with three-dimensional through pores is formed, significantly improving the dissolution rate; the gradient freeze-drying process enables the directional growth of ice crystals to form a channel structure; the gas pore-forming effect generated by adding sodium bicarbonate reduces the density of the embedding body; the polyphenolic substances in the fruit powder and sodium alginate have synergistic antioxidant effects. Gas pore-forming effect makes the density of the embedding body decrease; the polyphenolic substances in the fruit powder and sodium alginate have synergistic antioxidant effects.

[0032] Step S4: Mix the embedded ultramicro creatine zinc magnesium complex with erythritol and xylitol. Use a three-dimensional mixer to control the mixing at 20 rpm for 10 minutes. Among them, the water activity of the final mixture ≤ 0.3. Finally, perform ultraviolet sterilization to obtain the ultramicro creatine instant dissolution composition. This can improve the sweetness and taste of the product, reduce metallic and fishy flavors, and does not affect blood sugar; a high proportion of erythritol provides a strong sense of coolness and good particle fluidity. Controlling the fruit powder content can not only provide flavor, color, and natural antioxidant properties, but also prevent excessive water absorption or affect the dissolution performance of the main components, thus comprehensively solving the problem of the balance between taste and solubility.

[0033] In this technical solution, before ultraviolet sterilization, first perform hot air activation treatment at 30 - 45 °C for 20 minutes, and select the dual-wavelength alternating irradiation of 200 - 265 nm and 150 - 185 nm for the ultraviolet wavelength.

[0034] In this technical solution, after ultraviolet sterilization, place the composition in an environment with a humidity ≤ 10%RH and a temperature ≤ 10 °C for cooling and static equilibrium for 24 - 48 hours, and perform vacuum dehumidification packaging.

[0035] The second aspect of this application mentions an ultramicro creatine instant dissolution composition, which is prepared by using the preparation method of an ultramicro creatine instant dissolution composition mentioned in the first aspect. By weight percentage, it includes: Ultramicro creatine: 40% - 50%, erythritol: 30% - 40%, xylitol: 5% - 10%, fruit powder: 5% - 10%, zinc amino acid chelate calculated as zinc ion: 0.5% - 5%, magnesium amino acid chelate calculated as magnesium ion: 1% - 10%.

[0036] In this technical solution, the mass ratio of erythritol to xylitol is (1 - 3):1, and the total mass of the two accounts for 60 - 80% of the total mass of the ultramicro creatine instant dissolution composition.

[0037] In this technical solution, the fruit powder is blueberry powder or blackcurrant powder, and has been freeze-dried.

[0038] In response to the hydrolysis problem of creatine in the gastric acid environment, at the gastric stage, through the double-layer protection mechanism of physical barrier and chemical slow release formed by the hydroxypropyl methylcellulose enteric coating and the closed pore gel structure formed by freeze-drying. The enteric coating effectively resists strong acid erosion, and the microporous network generated by the sodium alginate gel through sodium bicarbonate pore formation can delay the hydrogen ion penetration rate, significantly inhibiting the hydrolysis reaction of creatine in the gastric acid environment.

[0039] During intestinal absorption, the zinc-magnesium amino acid chelate's carrier function is utilized to adjust the ratio of zinc to magnesium, enabling active transmembrane transport of ions. This process, coupled with the rapid dissolution of ultrafine creatine, creates a coupling effect: the ultrafine creatine particles are instantly released within the porous gel network, while the sustained release of trace zinc and magnesium ions guides the peptide transporter to efficiently capture creatine molecules, achieving dual-component co-transport.

[0040] The entire process avoids the formation of creatinine caused by ineffective hydrolysis, reducing the burden of kidney clearance; at the same time, the complete creatine molecules are directly absorbed through the intestines, reducing the liver's conversion and metabolic pressure, and ultimately forming an synergistic closed loop from protection to absorption.

[0041] The third aspect of this application relates to the use of an ultra-micro creatine flash dissolution composition in the preparation of a sports nutrition supplement, which is an instant powder, sports drink, or solid capsule. This composition has all the beneficial effects of the first aspect described above and will not be further elaborated here.

[0042] In order to better understand the technical solution, the exemplary embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. This application is based on verification experiments, and each embodiment / comparative example sets three test groups with the same parameters, which will not be repeated in the following.

[0043] Example 1

[0044] The raw materials used in this Example 1 are all commercially available conventional products; Creatine monohydrate: Supplier is Hubei Lingan Technology Co., Ltd., model number is 200mesh; Zinc glycinate: Supplier is Zhejiang Ruipu Pharmaceutical Raw Materials Co., Ltd., model number is Zn-Gly 400; Magnesium bisglycinate: supplier is Jiangsu Kexin Biotechnology Co., Ltd., model number is Mg-DGly 150; Sodium alginate: Supplier is Qingdao Mingyue Seaweed Group Co., Ltd., viscosity 500; Freeze-dried blueberry powder: The supplier is Qingdao Borne Hi-Tech Biotechnology Co., Ltd.

[0045] Composition formula: ultra-micro creatine 40g, zinc-magnesium amino acid chelate 8g (zinc 0.74g, magnesium 1g), sodium alginate 3g, freeze-dried blueberry fruit powder 6g, xylitol 5g, erythritol 30g, sodium bicarbonate 0.5g.

[0046] Preparation method: Preparation of Ultrafine Creatine: Creatine monohydrate was placed in a low-temperature nitrogen airflow mill at -8°C and a crushing pressure of 1.1 MPa, and pulverized until 99% of the particles were no larger than 15 μm. An ionizing air gun was used at a speed of 3 m / s to eliminate static electricity, resulting in ultrafine creatine powder.

[0047] Zinc-magnesium amino acid chelate coating: Zinc glycinate and magnesium diglycinate were mixed at a molar ratio of zinc to magnesium of 1:2. Through a fluidized bed spray coater, with hydroxypropyl methylcellulose as the coating material, the mass ratio of the coating material to the core material was 1:6, and the inlet air temperature was 55°C to form microcapsules with a particle size of 30 μm.

[0048] Construction of porous embedding complex: The obtained ultramicro creatine and the obtained zinc-magnesium microcapsules were dry-mixed; a mixed solution of a 2% sodium alginate solution and 6% freeze-dried blueberry fruit powder was sprayed in, and the spraying rate was controlled at 8 wt% / min; after adding 0.5% sodium bicarbonate and mixing, gradient freeze-drying was carried out.

[0049] Quick-freezing stage: Cool down to -45°C at a rate of 12°C / min and maintain for 1.5 h; Primary drying: Heat up to -18°C at a rate of 1°C / min and maintain for 1 h; Secondary drying: Heat up to -3°C at a rate of 1.2°C / min and maintain for 0.5 h; Final drying: Under a vacuum of less than 10 Pa, heat up to 35°C at a rate of 2°C / min and keep warm for 1.5 h.

[0050] Mixing and sterilization: The freeze-dried product, erythritol, and freeze-dried blueberry fruit powder were put into three-dimensional mixing, and mixed for ten minutes to reduce the water activity to below 0.3, and then activated by hot air at 35°C for fifteen minutes; After alternating ultraviolet irradiation in two bands for five minutes each, leave it to stand and equilibrate in an environment with a humidity of 8% and a temperature of 8°C for 36 hours.

[0051] Example 2

[0052] The difference between Example 2 and Example 1 is that blackcurrant powder is used instead of freeze-dried blueberry powder.

[0053] Comparative Example 1 The difference between Comparative Example 1 and Example 1 is that zinc lactate and magnesium sulfate are used instead of ultramicro creatine.

[0054] Comparative Example 2 The difference between Comparative Example 2 and Example 1 is that creatine hydrochloride is used instead of zinc-magnesium amino acid chelate.

[0055] Comparative Example 3 The difference between Comparative Example 3 and Example 1 is that the chelation of ultramicro creatine is omitted.

[0056] Product stability experiment; According to the "Technical Regulations for the Evaluation of Health Foods", the muscle synthesis-promoting supplements obtained in Examples 1 and 2 were placed under the conditions of 37 - 40°C and a humidity of 75%. Indexes such as total number of colonies, yeast, and mold that can represent the internal quality of the product were selected, sampled and measured once a month for three consecutive months, and the measured indexes were stable, which is equivalent to a storage period of two years.

[0057] Application effect experiment; Experimental subjects: 30 male basketball players, aged 20 ± 3 years, height 193 ± 5 cm, weight 85 ± 6 kg, training years 3. ± 1 year.

[0058] Grouping and intervention: Control group (15 people): taking dextrin + blueberry fruit powder placebo granules; Experimental group (15 people): taking the granule prepared in Example 1 of the present invention.

[0059] Dosage and cycle: Both groups took 10 g 30 minutes before daily training for 4 weeks.

[0060] Taboo control: Other nutritional products were prohibited during the experiment, and the training plans were the same.

[0061] Detection indicators and time points, detection time: before taking the medicine, 4 weeks after taking the medicine; Detection items: Serum testosterone: detected from the cubital vein blood in the early morning on an empty stomach; Muscle mass and muscle percentage: measured by a body composition analyzer.

[0062] Training arrangement: High-intensity basketball training uniformly formulated by the coach was carried out throughout the process.

[0063] Note: In this experiment, by comparing the changes in serum testosterone (a key anabolic hormone) and muscle mass, the promoting effect on muscle synthesis after exercise was verified. The core control variables were training intensity and nutritional product interference factors.

[0064] Test: One test was carried out before and after oral administration. Cubital vein blood was taken on an empty stomach in the early morning for serum testosterone detection; muscle percentage detection.

[0065] Sports training arrangement: During the whole experiment, the athletes carried out high-intensity training according to the coach's plan. No other nutritional products were taken by all the athletes during the experiment.

[0066] Main instruments: Radioimmunoassay was used for serum testosterone detection, and a KYT-88 type γ-counter was selected; A CTM-DX300 type body composition analyzer was used for body composition detection.

[0067] Data statistics: The obtained data was processed by Excel, and double-blind method and t-test were used for statistical analysis of the test data, which was expressed as mean ± SD.

[0068] ; Referring to Table 1, during the high-intensity training phase, the serum testosterone of the athletes in the control group decreased, and this decrease was extremely significant. In contrast, there was no significant difference in the serum testosterone level of the experimental group compared with that before the experiment. After testing, at the end of the experiment, there was an extremely significant difference in the testosterone levels between the experimental group and the control group.

[0069] ; As can be seen from referring to Table 2, the muscle percentage content of the athletes increased during the experiment, and there was a significant difference in the experimental group.

[0070] The ultramicro creatine instant dissolving composition prepared by the present invention is used to prepare a sports nutrition supplement, which helps to maintain the serum testosterone level of athletes during high-intensity training, thereby promoting muscle synthesis.

[0071] Simulated gastric juice stability verification experiment; By verifying the stability of different creatine preparations in simulated gastric juice (pH 1.5 - 3.5) for 2 hours, measuring the creatine loss rate, and detecting the creatinine production amount, the influence of different formulations on the creatine protection effect was evaluated.

[0072] Experimental instruments and equipment: Thermostatic shaking water bath THZ - 98A, Shanghai Yiheng Technology; High performance liquid chromatograph Agilent 1260 Infinity II; Centrifuge TG16 - WS, Hunan Xiangyi; Ultraviolet spectrophotometer Shimadzu UV - 2600.

[0073] Preparation of simulated gastric juice: Refer to the simulated gastric juice formula in the Chinese Pharmacopoeia: Pepsin (1:10000) 3.2 g / L; NaCl 2.0 g / L; Adjust the pH to 1.8 ± 0.2 with HCl.

[0074] The samples used the samples prepared in the above-mentioned examples and comparative examples, and their original data were detected.

[0075] Experimental steps Sample treatment: Take 100 mg of the sample for each group and add 10 mL of simulated gastric juice (pre - equilibrated at 37°C).

[0076] Thermostatic shaking: Shake at 37°C and 100 rpm for 2 hours.

[0077] Terminate the reaction: Immediately cool in an ice bath, centrifuge (10000 rpm, 10 min), and take the supernatant.

[0078] HPLC detection: Chromatographic conditions: C18 column (4.6×250 mm), mobile phase (0.1 M phosphate buffer: methanol = 95:5), flow rate 1.0 mL / min, detection wavelength 210 nm.

[0079] Standard curve: Creatine (0.1 - 10 mg / mL, r = 0.999), Creatinine (0.05 - 5 mg / mL, r = 0.998).

[0080] ; Referring to Table 3, Example 1 and Example 2, the creatine loss rate is ≤5%, indicating that the zinc-magnesium chelate microcapsules effectively block gastric acid, and the creatinine production is extremely low (<15 mg / g).

[0081] Creatine loss rate: Comparative Example 1 (ordinary creatine 80 μm): 30.0%, Example 1 (ultramicro creatine 12 μm): 4.99%. Ultramicroization increases the specific surface area, and the sodium alginate coating is more complete, extending the gastric acid penetration path.

[0082] The creatine loss rate of Comparative Example 3 is much higher than that of Example 1 and Example 2, indicating that the hydroxypropyl methylcellulose coating of the microcapsules forms a dense gel layer at pH < 3.

[0083] Verification experiment on the release performance in small intestine simulating fluid; To verify the release characteristics of the ultramicro creatine instant dissolution composition of the present application in the intestinal environment; Preparation of small intestine simulating fluid: Potassium dihydrogen phosphate 6.8 g / L, pancreatin 10 g / L, adjust pH to 6.8 ± 0.1 with NaOH; Experimental design: Example 1, Example 2; Experimental steps: 1. Take 100 mg of the sample and place it in a dialysis bag (MWCO 8 - 10 kDa), immerse it in 50 mL of SIF (37 °C).

[0084] 2. Magnetic stirring (50 rpm), take 1 mL of sample at 5, 10, 15, 20, 25, 30 min (supplement the same amount of fresh SIF).

[0085] 3. Detect the creatine concentration by HPLC and detect the concentration by AAS.

[0086] ; ; Referring to Table 4 and Table 5, Example 1 and Example 2 are both completely released (>98%) within 30 minutes, meeting the instant dissolution requirements, and the zinc and magnesium ions are released synchronously, which can optimize the intestinal absorption competition.

[0087] Note: All data were statistically tested (p < 0.05), n = 6.

[0088] Obviously, the above are merely examples given for clear illustration and not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to enumerate all implementation manners here. And the obvious changes or modifications derived therefrom still fall within the protection scope of this invention.

[0089] In the description of this invention, it should be understood that the terms "first" and "second" are only used for descriptive purposes and cannot be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features. In the description of this invention, "a plurality of" means two or more, unless otherwise specifically defined.

[0090] In the description of this specification, the description of terms such as "a", "some", "example", "specific example" or "some examples" etc. means that the specific features, structures, materials or characteristics described in connection with the or example are included in at least one or example of this invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same example. Moreover, the specific features, structures, materials or characteristics described can be combined in a suitable manner in any one or more or examples. In addition, without contradiction, those skilled in the art can combine and combine the different examples and the features of different examples described in this specification.

[0091] It can be understood that the above are exemplary and cannot be construed as a limitation on this invention. Those of ordinary skill in the art can make changes, modifications, substitutions and variations to the above within the scope of this invention.

Claims

1. A preparation method of an ultramicro creatine instant dissolving composition, characterized in that, Including: Crush creatine monohydrate to ≥500 mesh and perform static electricity elimination treatment to obtain ultramicro creatine; Mix zinc glycinate and magnesium diglycinate according to the molar ratio of Zn:Mg of 1:(2 - 3), and spray-coat to form microcapsules to obtain zinc-magnesium amino acid chelate Dry-mix the ultramicro creatine and the zinc-magnesium amino acid chelate, spray into the mixed solution of sodium alginate and fruit powder, and freeze-dry to form a porous embedding structure to obtain an ultramicro creatine zinc-magnesium complex; Mix the embedded ultramicro creatine zinc-magnesium complex with erythritol and xylitol, and perform ultraviolet sterilization to obtain an ultramicro creatine instant-soluble composition.

2. The preparation method of an ultramicro creatine instant-soluble composition according to claim 1, characterized in that Add the mixture of zinc glycinate and magnesium diglycinate into a fluidized bed coating equipment, use an atomization pressure of 0.4 - 0.6 MPa, and an inlet air temperature of 120 - 140 °C; In the mixed solution of sodium alginate and fruit powder, the concentration of sodium alginate is 1.5 - 2.5% w / v, and the content of fruit powder is 3 - 8% w / v; the liquid spraying rate during spraying is controlled at 5 - 10 wt% / min of the total weight of the mixed materials.

3. The preparation method of an ultramicro creatine instant-soluble composition according to claim 1, characterized in that Before freeze-drying, sodium bicarbonate with a mass fraction of 0.5% to 1% is added to the mixed solution to release gas during the freezing process.

4. The preparation method of an ultramicro creatine instant-soluble composition according to claim 1, characterized in that Freeze-drying is carried out by gradient cooling. First, cool to below -40 °C at a rate of 10 - 15 °C / min and hold for 1 - 2 hours for thorough freezing; then heat to -15 - 20 °C at a rate of 0.8 - 1.2 °C / min and hold for 1 hour; then heat to -5 - 0 °C at a rate of 1.0 - 1.5 °C / min and hold for 0.5 hour; finally, under a vacuum degree of <10 Pa, heat to 30 - 40 °C at a rate of 1.5 - 2.5 °C / min and keep warm for 1 - 2 hours until completely dry.

5. The preparation method of an ultramicro creatine instant-soluble composition according to claim 1, characterized in that The mass ratio of erythritol to xylitol is (1 - 3):1, and the total mass of the two accounts for 60 - 80% of the total mass of the ultramicro creatine instant-soluble composition.

6. The preparation method of an ultramicro creatine instant-soluble composition according to claim 1, characterized in that Before ultraviolet sterilization, first perform hot air activation treatment at 30 - 45 °C for 20 minutes, and select the dual wavelength bands of 200 - 265 nm and 150 - 185 nm for alternating irradiation.

7. The preparation method of an ultramicro creatine instant-soluble composition according to claim 1, characterized in that After ultraviolet sterilization, place the composition in an environment with a humidity ≤10% RH and a temperature ≤10 °C to cool and stand for 24 - 48 hours, and perform vacuum dehumidification packaging.

8. A superfine creatine instant dissolving composition, prepared by using the preparation method of a superfine creatine instant dissolving composition according to any one of claims 1-7, characterized in that, By weight percentage, including: Ultramicro creatine: 40% - 50%, erythritol: 30% - 40%, xylitol: 5% - 10%, fruit powder: 5% - 10%, zinc amino acid chelate calculated as zinc ion: 0.5% - 5%, magnesium amino acid chelate calculated as magnesium ion: 1% - 10%.

9. The composition according to claim 8, characterized in that, The fruit powder is blueberry powder or blackcurrant powder, and has been subjected to freeze-drying treatment.

10. Use of the composition according to claim 8 in the preparation of a sports nutrition supplement, characterized in that, The supplement is an instant powder, a sports drink, or a solid capsule.

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