Preparation method of sodium hyaluronate and chondroitin composite oral supplement

Abstract

The invention discloses a preparation method of a sodium hyaluronate and chondroitin composite oral supplement, and relates to the technical field of preparation of nutritional supplements. The compound oral supplement is prepared from the following materials in parts: 20 to 50 parts of sodium hyaluronate, 30 to 60 parts of chondroitin, 100 to 200 parts of edible glucose, 50 to 100 parts of sorbitol, 80 to 150 parts of maltodextrin, 20 to 40 parts of bone collagen peptide, 3 to 8 parts of magnesium stearate and 5 to 10 parts of a compound coating agent. According to the preparation method of the compound oral supplement, raw material selection and a preparation process are strictly controlled, so that high activity of sodium hyaluronate and chondroitin is ensured, excellent properties of the sodium hyaluronate and chondroitin in the aspects of moisturizing, joint lubrication and cartilage repair are fully exerted, auxiliary materials are reasonably selected, the sweetness and taste of the product are optimized, and the compound oral supplement is prepared. According to the preparation method, strict quality control standards are formulated for all links, it is ensured that the product quality is stable and reliable, the production efficiency and the product uniformity are improved, and the preparation method is suitable for a wide range of people.

Description

Technical Field

[0001] The invention relates to the technical field of nutritional supplement preparation, and in particular to a method for preparing a sodium hyaluronate and chondroitin composite oral supplement. Background Art

[0002] As people's living standards improve, they pay more and more attention to health and beauty. Sodium hyaluronate and chondroitin, as ingredients that play an important role in joint health maintenance and medical beauty, have received widespread attention.

[0003] Sodium hyaluronate, also known as hyaluronic acid, is an acidic mucopolysaccharide that is widely present in the skin, joint cavity and other tissues in the human body. It has excellent water retention properties, and its aqueous solution has high viscoelasticity. It can form a lubricating and elastic protective film in the joint cavity, reducing the friction between the joint surfaces; in terms of skin, it can make the skin moisturized and plump, and reduce wrinkles. Chondroitin, usually referring to chondroitin sulfate, is also an acidic mucopolysaccharide and one of the important components of cartilage. It can promote the metabolism and proliferation of chondrocytes, increase the synthesis of cartilage matrix, and improve the elasticity and toughness of cartilage; in the field of skin, it can promote the synthesis of collagen and elastic fibers in the skin, and increase the elasticity and firmness of the skin.

[0004] At present, although there are some composite products of sodium hyaluronate and chondroitin on the market, there are many problems in the preparation methods. Some products fail to fully consider the characteristics of the two ingredients during the preparation process, resulting in reduced activity of the effective ingredients and affecting the efficacy of the product. For example, some preparation processes may reduce the moisturizing properties of sodium hyaluronate or weaken the ability of chondroitin to promote cartilage repair. At the same time, the existing products are not reasonable in the selection of excipients and formula design, and the taste is not good, which affects the consumer's taking experience and leads to reduced compliance. In addition, some preparation methods lack strict standards for quality control in the production process, and the product quality is uneven, which makes it difficult to meet consumers' demand for high-quality products. In this regard, we propose a preparation method for a composite oral supplement of sodium hyaluronate and chondroitin. Summary of the invention

[0005] In order to solve the above technical problems, a method for preparing a composite oral supplement of sodium hyaluronate and chondroitin is provided. This technical solution solves the problem that some of the above products fail to fully consider the characteristics of the two ingredients during the preparation process, resulting in reduced activity of the effective ingredients and affecting the efficacy of the product.

[0006] In order to achieve the above purpose, the technical solution adopted by the present invention is:

[0007] The invention discloses a method for preparing a composite oral supplement of sodium hyaluronate and chondroitin. The composite oral supplement is prepared from the following materials: 20-50 parts of sodium hyaluronate, 30-60 parts of chondroitin, 100-200 parts of edible glucose, 50-100 parts of sorbitol, 80-150 parts of maltodextrin, 20-40 parts of collagen peptide, 3-8 parts of magnesium stearate and 5-10 parts of a composite coating agent.

[0008] Preferably, the composite oral supplement is prepared from the following materials: 30 parts of sodium hyaluronate, 40 parts of chondroitin, 150 parts of edible glucose, 70 parts of sorbitol, 120 parts of maltodextrin, 30 parts of collagen peptide, 5 parts of magnesium stearate, and 8 parts of compound coating agent.

[0009] Preferably, the preparation method is:

[0010] S1. Prepare materials: 30 parts of sodium hyaluronate, 40 parts of chondroitin, 150 parts of edible glucose, 70 parts of sorbitol, 120 parts of maltodextrin, 30 parts of collagen peptide, 5 parts of magnesium stearate, and 8 parts of compound coating agent;

[0011] S2. Mixing raw materials: putting edible glucose, sorbitol and maltodextrin into a high-speed mixer, stirring at a speed of 300-500 r / min for 15-30 min to fully mix them, and obtaining a mixture A;

[0012] S3. Add active ingredients: add sodium hyaluronate, chondroitin and collagen peptide to mixture A in sequence, adjust the speed of the mixer to 200-400 r / min, and continue stirring for 30-60 min to ensure that the ingredients are evenly dispersed to form mixture B;

[0013] S4, granulation: add an appropriate amount of purified water to the mixture B to prepare a soft material, the moisture of the soft material is suitable to be able to form a ball when held by hand and to fall apart when lightly pressed, and use a swing granulator with a screen aperture of 16-20 mesh to obtain wet granules;

[0014] S5. Drying: Place the wet granules in a hot air circulation drying oven for drying. The drying temperature is controlled at 50-70°C and the drying time is 2-4 hours to reduce the moisture content of the granules to 3%-5%;

[0015] S6. Granulation: Use a granulator to granulate the dried granules to remove the sticky large particles and fine powder. The granulation screen has an aperture of 18-22 meshes.

[0016] S7, adding lubricant: adding magnesium stearate to the granules after granulation, stirring at a speed of 150-300 r / min for 10-20 min to uniformly mix them to obtain granules to be compressed into tablets;

[0017] S8, tableting: Use a rotary tablet press to press the granules to be pressed into tablets. Adjust the tablet press pressure according to product design requirements to control the tablet weight difference within ±5% and the hardness within 50-100N;

[0018] S9, coating: dissolve the compound coating agent in an appropriate amount of ethanol solution to prepare a coating solution with a concentration of 10%-20%. Use a high-efficiency coating machine to coat the compressed tablets. During the coating process, control the inlet air temperature to 40-60℃, the outlet air temperature to 30-50℃, and the coating weight gain to 2%-5%;

[0019] S10. Quality testing: performing quality testing on the prepared composite oral supplement, wherein the quality testing includes appearance, content determination, disintegration time and microbial limit;

[0020] S11. Packaging: The qualified products shall be packaged in bottles and stored in a dry, cool and ventilated environment.

[0021] Preferably, the preparation process of sodium hyaluronate is:

[0022] A microbial strain producing hyaluronic acid is selected and fermented in a fermentation medium containing a carbon source, a nitrogen source, an inorganic salt and trace elements, wherein the carbon source requires a glucose concentration of 20-40 g / L, the nitrogen source requires a yeast powder concentration of 5-10 g / L, the inorganic salt requires a potassium dihydrogen phosphate concentration of 1-3 g / L and a magnesium sulfate concentration of 0.5-1.5 g / L;

[0023] The fermentation temperature is controlled at 35-38°C, the pH value is maintained at 7.0-7.5 by adding ammonia water during the fermentation process, the dissolved oxygen is controlled at 30%-50%, and the fermentation time is 48-72h;

[0024] After the fermentation is finished, the bacteria are removed by centrifugation and the fermentation supernatant is collected;

[0025] An equal volume of anhydrous ethanol is added to the fermentation supernatant for precipitation, the precipitate is collected by centrifugation, the precipitate is dissolved with deionized water, and then purified by an ion exchange resin column to remove impurity ions, and finally spray-dried to obtain a finished sodium hyaluronate product with a purity of not less than 95%.

[0026] Preferably, chondroitin is extracted from animal cartilage, and the specific extraction process is:

[0027] Select beef, pig or chicken cartilage, clean it and mince it into pieces with a particle size less than 5 mm;

[0028] Add the cartilage fragments to 5-10 times the volume of 0.1-0.3 mol / L hydrochloric acid solution, and stir and extract at 40-60°C for 2-4 hours;

[0029] After the extraction, the pH value was adjusted to 7.0-8.0 with 1 mol / L sodium hydroxide solution, the insoluble impurities were removed by filtration, and the filtrate was collected;

[0030] Add 3-5 times the volume of ethanol to the filtrate, let it stand at -5-5°C for 12-24 hours, collect the precipitate by centrifugation, wash the precipitate with anhydrous ethanol 2-3 times, and dry it to obtain crude chondroitin;

[0031] The crude chondroitin is dissolved in an appropriate amount of deionized water, and further purified by gel column chromatography. The eluate containing chondroitin is collected, concentrated and dried to obtain the finished chondroitin, the sulfation degree of which is not less than 80%.

[0032] Preferably, in step S2, the high-speed stirrer is made of stainless steel, the inner wall is smooth and has no dead angles, the stirring blade is a three-blade spiral, and the ratio of the blade diameter to the inner diameter of the stirring drum is 0.4-0.6;

[0033] The temperature was controlled at 20-30°C at the beginning of the mixing process. When the mixing process was halfway through, the temperature was raised to 35°C at a rate of 1°C / min and the mixture was continuously stirred until it was completely mixed.

[0034] Preferably, during the process of adding active ingredients in step S3, when the amount of sodium hyaluronate added is 0-10 parts, the addition rate is 1-2 g / min; when the amount of sodium hyaluronate added is in the range of 11-20 parts, the rate is adjusted to 0.8-1.5 g / min; when the amount of sodium hyaluronate added is 21-30 parts, it is reduced to 0.5-1 g / min; when the amount of sodium hyaluronate added exceeds 30 parts until all parts are added, it is maintained at 0.3-0.8 g / min;

[0035] The addition rate of chondroitin and collagen peptide is related to the addition amount of sodium hyaluronate. When the addition amount of sodium hyaluronate is 0-20 parts, the addition rate of chondroitin is 1.5-2.5 g / min, and the addition rate of collagen peptide is 0.8-1.2 g / min; when the addition amount of sodium hyaluronate is 21-40 parts, the addition rate of chondroitin is 1-2 g / min, and the addition rate of collagen peptide is 0.6-1 g / min; when the addition amount of sodium hyaluronate exceeds 40 parts, the addition rate of chondroitin is 0.5-1.5 g / min, and the addition rate of collagen peptide is 0.4-0.8 g / min.

[0036] The angle of the stirring blade changes with the amount of active ingredients added. Initially, the angle between the blade and the horizontal is 30°-40°, and it is adjusted every time 10 parts of active ingredients are added. The active ingredients refer to the sum of sodium hyaluronate, chondroitin and collagen peptides. The final angle reaches 45°-55°.

[0037] Preferably, during the granulation process in step S4, the amount of purified water added is 15%-25% of the weight of the mixture B. To prevent the soft material from sticking, an appropriate amount of anti-sticking agent, such as silicon dioxide, can be added to the mixture B before granulation, and the added amount is 0.5%-1% of the weight of the mixture B. The oscillation frequency of the oscillating granulator is controlled at 30-50 times / min.

[0038] Preferably, during the drying process in step S5, the wind speed of the hot air circulation drying oven is controlled at 1-3 m / s, and the particles are turned over every 1 hour to ensure uniform drying;

[0039] After drying, use a rapid moisture meter to test the moisture content of the particles. If the moisture content does not meet the requirements, extend the drying time and adjust the drying temperature.

[0040] Preferably, in the quality inspection of step S10, the appearance inspection requires that the tablet surface is smooth, uniform in color, and free of obvious spots, cracks, and deformations;

[0041] The content was determined by high performance liquid chromatography, and the content of sodium hyaluronate and chondroitin should be within the range of 90%-110% of the labeled amount respectively;

[0042] The disintegration time should not exceed 60 minutes. The microbial limit test must comply with the provisions of the "Chinese Pharmacopoeia". The total number of bacteria shall not exceed 1000 cfu / g, the total number of molds and yeasts shall not exceed 100 cfu / g, and pathogenic bacteria shall not be detected.

[0043] Compared with the prior art, the present invention has the following beneficial effects:

[0044] The preparation method of the composite oral supplement proposed in the present invention ensures the high activity of sodium hyaluronate and chondroitin by strictly controlling the selection of raw materials and the preparation process, gives full play to their excellent performance in moisturizing, joint lubrication and cartilage repair, reasonably selects auxiliary materials, optimizes the sweetness and taste of the product, and meets the health needs of special groups of people. The preparation method establishes strict quality control standards for each link to ensure stable and reliable product quality, adopts advanced professional equipment and precise parameter control, improves production efficiency and product uniformity, the product is suitable for a wide range of people, is convenient for long-term use, effectively regulates joint and skin conditions, and has excellent packaging materials and storage conditions, which further extend the shelf life of the product and ensure the quality of the product purchased by consumers. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 The present invention is a flow chart of a method for preparing a composite oral supplement. DETAILED DESCRIPTION

[0046] The following description is used to disclose the present invention so that those skilled in the art can implement the present invention. The preferred embodiments described below are only examples, and those skilled in the art may think of other obvious variations.

[0047] The invention discloses a method for preparing a composite oral supplement of sodium hyaluronate and chondroitin. The composite oral supplement is prepared from the following materials: 20-50 parts of sodium hyaluronate, 30-60 parts of chondroitin, 100-200 parts of edible glucose, 50-100 parts of sorbitol, 80-150 parts of maltodextrin, 20-40 parts of collagen peptide, 3-8 parts of magnesium stearate and 5-10 parts of a composite coating agent.

[0048] The composite oral supplement is specifically prepared from the following materials: 30 parts of sodium hyaluronate, 40 parts of chondroitin, 150 parts of edible glucose, 70 parts of sorbitol, 120 parts of maltodextrin, 30 parts of collagen peptide, 5 parts of magnesium stearate, and 8 parts of compound coating agent.

[0049] Reference Figure 1 As shown, the preparation process of the composite oral supplement is as follows:

[0050] Material preparation: Strictly follow the formula requirements, accurately weigh 30 parts of sodium hyaluronate, 40 parts of chondroitin, 150 parts of edible glucose, 70 parts of sorbitol, 120 parts of maltodextrin, 30 parts of collagen peptide, 5 parts of magnesium stearate and 8 parts of compound coating agent. Ensure that the quality of each raw material is excellent and meets the corresponding quality standards, laying the foundation for the subsequent preparation of high-quality products.

[0051] Initial mixing of raw materials: put edible glucose, sorbitol and maltodextrin into a high-speed mixer. The mixer is made of stainless steel, and its inner wall is smooth without dead corners, which can effectively avoid material residue and cross contamination. The stirring blade is designed as a three-leaf spiral, and the ratio of the blade diameter to the inner diameter of the mixing barrel is maintained at 0.4-0.6. This design can provide strong and uniform stirring force. In the initial stage of stirring, the temperature is controlled at 20-30℃, and the speed is stirred at 300-500r / min for 15-30min. When the mixing process is more than halfway, slowly heat up to 35℃ at a rate of 1℃ / min, and continue stirring until the raw materials are fully mixed to form a mixture A. This process is designed to initially fuse the basic raw materials and create good conditions for the subsequent addition of active ingredients.

[0052] Active ingredient addition and mixing: Sodium hyaluronate, chondroitin and collagen peptide are added to mixture A in sequence. During the addition process, the mixer speed is adjusted to 200-400r / min. The addition rate of sodium hyaluronate has specific rates at different stages, 1-2g / min for 0-10 parts, 0.8-1.5g / min for 11-20 parts, 0.5-1g / min for 21-30 parts, and 0.3-0.8g / min for more than 30 parts until the addition is completed. The addition rate of chondroitin and collagen peptide is related to the amount of sodium hyaluronate added. When it is 0-20 parts, the chondroitin is 1.5-2.5g / min and the collagen peptide is 0.8-1.2g / min; when it is 21-40 parts, the chondroitin is 1-2g / min and the collagen peptide is 0.6-1g / min; when it exceeds 40 parts, the chondroitin is 0.5-1.5g / min and the collagen peptide is 0.4-0.8g / min. At the same time, the angle of the stirring blade changes with the amount of active ingredient added. The initial angle is 30°-40°, and it is adjusted once every 10 parts of active ingredient is added, and the final angle reaches 45°-55°. Continue stirring for 30-60 minutes to ensure that each active ingredient is evenly dispersed to form mixture B.

[0053] Granulation: Add an appropriate amount of purified water to mixture B, the amount of purified water added is 15%-25% of the weight of mixture B. To prevent the soft material from sticking, an appropriate amount of silicon dioxide can be added to mixture B as an anti-sticking agent before granulation, the amount of which is 0.5%-1% of the weight of mixture B. Subsequently, a swing granulator is used to granulate, the swing frequency is controlled at 30-50 times / min, and the mesh size is selected to be 16-20 mesh to obtain wet granules. At this time, the humidity of the soft material should reach the ideal state of being able to form a ball when held by hand and to fall apart when lightly pressed.

[0054] Drying: Place the wet particles in a hot air circulation drying oven and dry them. The drying temperature is controlled at 50-70℃ and the wind speed is set at 1-3m / s. Turn the particles every 1 hour to ensure uniform drying. The drying time is 2-4 hours. After drying, use a moisture rapid tester to test the moisture content of the particles and reduce it to 3%-5%. If the moisture content does not meet the standard, the drying time needs to be extended or the drying temperature needs to be adjusted accordingly.

[0055] Granulation: Use a granulator to granulate the dried granules to remove sticky large particles and fine powder. The sieve aperture of the granulation is selected to be 18-22 mesh to ensure the uniformity and fluidity of the granules and prepare for the subsequent tableting process.

[0056] Lubricant addition: Add magnesium stearate to the granules after granulation, stir at a speed of 150-300r / min for 10-20min to evenly distribute the lubricant and obtain the granules to be tableted, ensure the smooth tableting process and prevent the granules from sticking.

[0057] Tablet pressing: Use a rotary tablet press to press the granules to be pressed into tablets. According to the product design requirements, the tablet press pressure is accurately adjusted to control the tablet weight difference within ±5% and the hardness within 50-100N to ensure that the tablet quality meets the standards and meets the needs of consumers.

[0058] Coating: Dissolve the compound coating agent in an appropriate amount of ethanol solution to prepare a coating solution with a concentration of 10%-20%. Use a high-efficiency coating machine to coat the compressed tablets. During the coating process, the inlet air temperature is controlled at 40-60℃, the outlet air temperature is controlled at 30-50℃, and the coating weight gain is controlled at 2%-5%. Coating can improve the appearance of tablets, improve product stability, and extend shelf life.

[0059] Quality inspection: Conduct comprehensive quality inspection on the prepared compound oral supplements. Appearance inspection requires that the tablet surface is smooth, uniform in color, without obvious spots, cracks and deformation; the content is determined by high performance liquid chromatography, and the content of sodium hyaluronate and chondroitin should be within the range of 90%-110% of the labeled amount respectively; the disintegration time should not exceed 60 minutes; the microbial limit test must strictly comply with the provisions of the "Chinese Pharmacopoeia", the total number of bacteria shall not exceed 1000 cfu / g, the total number of molds and yeasts shall not exceed 100 cfu / g, and pathogenic bacteria shall not be detected.

[0060] Packaging and storage: Pack qualified products in bottles. Store the products in a dry, cool, ventilated environment, avoid direct sunlight and high temperature and humidity to ensure that the product quality is not affected within the shelf life.

[0061] In the material preparation stage, accurate weighing of raw materials and ensuring high quality lays a solid foundation for product quality. When the raw materials are initially mixed, the specific mixer design and stirring conditions allow the basic raw materials to be fully integrated, creating good conditions for the subsequent addition of active ingredients. During the addition of active ingredients, the addition rate and the angle of the stirring blades are strictly controlled to ensure that the active ingredients are evenly dispersed. In the steps of granulation, drying, and granulation, the parameters are precisely controlled to make the particles reach the ideal state and ensure stable product quality. The addition of lubricants ensures smooth tableting and avoids sticking problems. Strict control of weight differences and hardness in the tableting process meets quality standards. Coating not only improves the appearance, but also improves stability and extends the shelf life. Comprehensive quality testing covers appearance, content, disintegration time and microbial limits to ensure product safety and effectiveness. Finally, the appropriate packaging and storage method can maintain product quality during the shelf life, allowing consumers to use it with confidence.

[0062] Preparation process of sodium hyaluronate

[0063] Select high-quality microbial strains that produce hyaluronic acid and place them in a fermentation medium containing specific ingredients for fermentation. The carbon source in the culture medium requires a glucose concentration of 20-40g / L, the nitrogen source requires a yeast powder concentration of 5-10g / L, and the inorganic salt requires a potassium dihydrogen phosphate concentration of 1-3g / L and a magnesium sulfate concentration of 0.5-1.5g / L. The fermentation temperature is strictly controlled at 35-38°C, and the pH value is maintained at 7.0-7.5 by adding ammonia water during the fermentation process. The dissolved oxygen is controlled at 30%-50%, and the fermentation time is 48-72h. After the fermentation is completed, the bacteria are removed by centrifugation and the fermentation supernatant is collected. Then, an equal volume of anhydrous ethanol is added to the supernatant for precipitation, the precipitate is collected by centrifugation, dissolved in deionized water, purified by an ion exchange resin column, impurity ions are removed, and finally spray dried to obtain a sodium hyaluronate product with a purity of not less than 95%.

[0064] The selection of high-quality microbial strains lays the foundation for the production of high-quality sodium hyaluronate. The concentration of each component of the culture medium is accurately defined to provide a suitable environment for strain growth and hyaluronic acid synthesis. The fermentation temperature, pH value, dissolved oxygen and time are strictly controlled to ensure a stable and efficient fermentation process, which is conducive to increasing the yield of hyaluronic acid. The centrifugation method is used to remove the bacteria, which is simple and efficient to operate. The use of anhydrous ethanol precipitation, ion exchange resin column purification and other steps can effectively remove impurities, so that the purity of the final product is not less than 95%, ensuring the quality of sodium hyaluronate, and can better meet the demand for high-purity raw materials in the fields of medicine and cosmetics.

[0065] Chondroitin extraction process

[0066] Select cattle, pig or chicken cartilage, wash and mince into pieces with a particle size of less than 5mm. Add the cartilage pieces to 5-10 times the volume of 0.1-0.3mol / L hydrochloric acid solution, and stir and extract at 40-60℃ for 2-4h. After the extraction, adjust the pH value to 7.0-8.0 with 1mol / L sodium hydroxide solution, filter to remove insoluble impurities, and collect the filtrate. Add 3-5 times the volume of ethanol to the filtrate, let it stand at -5-5℃ for 12-24h, collect the precipitate by centrifugation, wash the precipitate with anhydrous ethanol 2-3 times, and dry it to obtain crude chondroitin. Dissolve the crude chondroitin in an appropriate amount of deionized water, further purify it by gel column chromatography, collect the eluate containing chondroitin, concentrate and dry it to obtain the finished chondroitin, and its sulfation degree is not less than 80%.

[0067] The material is taken from common bovine, pig or chicken cartilage, which has a wide range of sources. The pretreatment of washing and mincing creates favorable conditions for subsequent extraction. The use of a hydrochloric acid solution of a specific concentration and stirring extraction at an appropriate temperature can efficiently dissolve chondroitin. Acid-base adjustment and filtration remove impurities to make the filtrate relatively pure. The crude chondroitin is obtained by ethanol precipitation, which is relatively easy to operate. It is then further purified by gel column chromatography to greatly improve the purity of chondroitin. The final product has a sulfation degree of not less than 80%, which ensures the biological activity and quality of chondroitin, can meet the needs of the pharmaceutical, health care and other industries for highly active chondroitin, and effectively guarantee the efficacy of the product.

[0068] The preparation process of the compound coating agent starts with the preparation of raw materials. According to the mass ratio of polyvinyl alcohol, polyethylene glycol and titanium dioxide of 3:2:1, each raw material is accurately weighed. Among them, polyvinyl alcohol must be selected from pharmaceutical grade to ensure that its alcoholysis degree is 85%-90% and the degree of polymerization is 1750±50 to optimize the film-forming performance; polyethylene glycol should be selected from products with a molecular weight of 4000-6000 to ensure good solubility and flexibility in the system; titanium dioxide should be food-grade anatase type with a particle size controlled at 20-50 nanometers to improve dispersibility and hiding power.

[0069] Next is the dissolution and mixing step. Slowly add the weighed polyvinyl alcohol into deionized water at 80-90°C, stirring at 200-300r / min for 1-2 hours until the solution is clear. Then, cool the solution to 50-60°C, add the weighed polyethylene glycol, and continue stirring at 150-200r / min for 30-60 minutes to fully mix the two to form a uniform viscous solution.

[0070] Finally, the titanium dioxide is dispersed, degassed and the finished product is packaged. Ultrasonic disperse the titanium dioxide in anhydrous ethanol for 15-20 minutes, then slowly add it to the above mixed solution, and stir it at a high speed of 800-1000r / min for 1-2 hours to ensure that the titanium dioxide is evenly dispersed. After that, place the solution in a vacuum degassing device and degas for 15-30 minutes at a vacuum degree of -0.08 to -0.1MPa to remove bubbles. After degassing, transfer the compound coating agent to a clean and dry packaging container while it is hot and seal it for storage. It should be kept cool and dry during storage, and the temperature should be controlled at 5-25℃. Avoid direct sunlight and high temperature environment to prevent changes in the performance of the coating agent.

[0071] The use process of the present invention is: S1, preparing materials; S2, mixing raw materials; S3, adding active ingredients; S4, granulation; S5, drying; S6, granulation; S7, adding lubricant; S8, tableting; S9, coating; S10, quality inspection; S11, packaging.

[0072] In summary, the advantages of the present invention are: the method ensures high activity of sodium hyaluronate and chondroitin, and synergistically exerts joint and skin health care effects; optimizes taste by selecting auxiliary materials, taking into account the needs of special groups; strict quality control and scientific preparation process ensure stable product quality and high production efficiency; the product is widely applicable and meets the needs of patients with joint diseases, middle-aged and elderly people and skin care; high-quality packaging and storage conditions extend the shelf life and ensure product quality. In summary, the invention has advantages in ingredients, taste, quality, process, applicability, packaging and storage, and has broad market prospects.

[0073] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions only describe the principles of the present invention. The present invention may be subject to various changes and improvements without departing from the spirit and scope of the present invention. These changes and improvements fall within the scope of the present invention. The scope of protection claimed by the present invention is defined by the attached claims and their equivalents.

Claims

1. A method for preparing a sodium hyaluronate and chondroitin composite oral supplement, characterized in that: The composite oral supplement is prepared from the following materials: 20-50 parts of sodium hyaluronate, 30-60 parts of chondroitin, 100-200 parts of edible glucose, 50-100 parts of sorbitol, 80-150 parts of maltodextrin, 20-40 parts of collagen peptide, 3-8 parts of magnesium stearate, and 5-10 parts of a composite coating agent.

2. The method for preparing the sodium hyaluronate and chondroitin composite oral supplement according to claim 1, characterized in that: The composite oral supplement is specifically prepared from the following materials: 30 parts of sodium hyaluronate, 40 parts of chondroitin, 150 parts of edible glucose, 70 parts of sorbitol, 120 parts of maltodextrin, 30 parts of collagen peptide, 5 parts of magnesium stearate, and 8 parts of compound coating agent.

3. The method for preparing the sodium hyaluronate and chondroitin composite oral supplement according to claim 1, characterized in that: The preparation method is: S1. Prepare materials: 30 parts of sodium hyaluronate, 40 parts of chondroitin, 150 parts of edible glucose, 70 parts of sorbitol, 120 parts of maltodextrin, 30 parts of collagen peptide, 5 parts of magnesium stearate, and 8 parts of compound coating agent; S2. Mixing raw materials: putting edible glucose, sorbitol and maltodextrin into a high-speed mixer, stirring at a speed of 300-500 r / min for 15-30 min to fully mix them, and obtaining a mixture A; S3. Add active ingredients: add sodium hyaluronate, chondroitin and collagen peptide to mixture A in sequence, adjust the speed of the mixer to 200-400 r / min, and continue stirring for 30-60 min to ensure that the ingredients are evenly dispersed to form mixture B; S4, granulation: add an appropriate amount of purified water to the mixture B to prepare a soft material, the moisture of the soft material is suitable to be able to form a ball when held by hand and to fall apart when lightly pressed, and use a swing granulator with a screen aperture of 16-20 mesh to obtain wet granules; S5. Drying: Place the wet granules in a hot air circulation drying oven for drying. The drying temperature is controlled at 50-70°C and the drying time is 2-4 hours to reduce the moisture content of the granules to 3%-5%; S6. Granulation: Use a granulator to granulate the dried granules to remove the sticky large particles and fine powder. The granulation screen has an aperture of 18-22 meshes. S7, adding lubricant: adding magnesium stearate to the granules after granulation, stirring at a speed of 150-300 r / min for 10-20 min to uniformly mix them to obtain granules to be compressed into tablets; S8, tableting: Use a rotary tablet press to press the granules to be pressed into tablets. Adjust the tablet press pressure according to product design requirements to control the tablet weight difference within ±5% and the hardness within 50-100N; S9, coating: dissolve the compound coating agent in an appropriate amount of ethanol solution to prepare a coating solution with a concentration of 10%-20%. Use a high-efficiency coating machine to coat the compressed tablets. During the coating process, control the inlet air temperature to 40-60℃, the outlet air temperature to 30-50℃, and the coating weight gain to 2%-5%; S10. Quality testing: performing quality testing on the prepared composite oral supplement, wherein the quality testing includes appearance, content determination, disintegration time and microbial limit; S11. Packaging: The qualified products shall be packaged in bottles and stored in a dry, cool and ventilated environment.

4. The method for preparing the sodium hyaluronate and chondroitin composite oral supplement according to claim 1, characterized in that: The preparation process of sodium hyaluronate is: A microbial strain producing hyaluronic acid is selected and fermented in a fermentation medium containing a carbon source, a nitrogen source, an inorganic salt and trace elements, wherein the carbon source requires a glucose concentration of 20-40 g / L, the nitrogen source requires a yeast powder concentration of 5-10 g / L, the inorganic salt requires a potassium dihydrogen phosphate concentration of 1-3 g / L and a magnesium sulfate concentration of 0.5-1.5 g / L; The fermentation temperature is controlled at 35-38°C, the pH value is maintained at 7.0-7.5 by adding ammonia water during the fermentation process, the dissolved oxygen is controlled at 30%-50%, and the fermentation time is 48-72h; After the fermentation is finished, the bacteria are removed by centrifugation and the fermentation supernatant is collected; An equal volume of anhydrous ethanol is added to the fermentation supernatant for precipitation, the precipitate is collected by centrifugation, the precipitate is dissolved with deionized water, and then purified by an ion exchange resin column to remove impurity ions, and finally spray-dried to obtain a finished sodium hyaluronate product with a purity of not less than 95%.

5. The method for preparing the sodium hyaluronate and chondroitin composite oral supplement according to claim 1, characterized in that: Chondroitin is extracted from animal cartilage. The specific extraction process is: Select beef, pig or chicken cartilage, clean it and mince it into pieces with a particle size less than 5 mm; Add the cartilage fragments to 5-10 times the volume of 0.1-0.3 mol / L hydrochloric acid solution, and stir and extract at 40-60°C for 2-4 hours; After the extraction, the pH value was adjusted to 7.0-8.0 with 1 mol / L sodium hydroxide solution, the insoluble impurities were removed by filtration, and the filtrate was collected; Add 3-5 times the volume of ethanol to the filtrate, let it stand at -5-5°C for 12-24 hours, collect the precipitate by centrifugation, wash the precipitate with anhydrous ethanol 2-3 times, and dry it to obtain crude chondroitin; The crude chondroitin is dissolved in an appropriate amount of deionized water, and further purified by gel column chromatography. The eluate containing chondroitin is collected, concentrated and dried to obtain the finished chondroitin, the sulfation degree of which is not less than 80%.

6. The method for preparing the sodium hyaluronate and chondroitin composite oral supplement according to claim 3, characterized in that: In step S2, the high-speed mixer is made of stainless steel, with a smooth inner wall and no dead corners. The stirring blade is a three-blade spiral type, and the ratio of the blade diameter to the inner diameter of the mixing drum is 0.4-0.6; The temperature was controlled at 20-30°C at the beginning of the mixing process. When the mixing process was halfway through, the temperature was raised to 35°C at a rate of 1°C / min and the mixture was continuously stirred until it was completely mixed.

7. The method for preparing the sodium hyaluronate and chondroitin composite oral supplement according to claim 3, characterized in that: During the process of adding active ingredients in step S3, when the amount of sodium hyaluronate added is 0-10 parts, the addition rate is 1-2 g / min; when the amount of sodium hyaluronate added is in the range of 11-20 parts, the rate is adjusted to 0.8-1.5 g / min; when the amount of sodium hyaluronate added is 21-30 parts, it is reduced to 0.5-1 g / min; when the amount of sodium hyaluronate added exceeds 30 parts until all parts are added, it is maintained at 0.3-0.8 g / min; The addition rate of chondroitin and collagen peptide is related to the addition amount of sodium hyaluronate. When the addition amount of sodium hyaluronate is 0-20 parts, the addition rate of chondroitin is 1.5-2.5 g / min, and the addition rate of collagen peptide is 0.8-1.2 g / min; when the addition amount of sodium hyaluronate is 21-40 parts, the addition rate of chondroitin is 1-2 g / min, and the addition rate of collagen peptide is 0.6-1 g / min; when the addition amount of sodium hyaluronate exceeds 40 parts, the addition rate of chondroitin is 0.5-1.5 g / min, and the addition rate of collagen peptide is 0.4-0.8 g / min. The angle of the stirring blade changes with the amount of active ingredients added. Initially, the angle between the blade and the horizontal is 30°-40°, and it is adjusted every time 10 parts of active ingredients are added. The active ingredients refer to the sum of sodium hyaluronate, chondroitin and collagen peptides. The final angle reaches 45°-55°.

8. The method for preparing the sodium hyaluronate and chondroitin composite oral supplement according to claim 3, characterized in that: During the granulation process in step S4, the amount of purified water added is 15%-25% of the weight of the mixture B. To prevent the soft material from sticking, an appropriate amount of anti-sticking agent, such as silicon dioxide, can be added to the mixture B before granulation, and the added amount is 0.5%-1% of the weight of the mixture B. The oscillation frequency of the oscillating granulator is controlled at 30-50 times / min.

9. The method for preparing the sodium hyaluronate and chondroitin composite oral supplement according to claim 3, characterized in that: During the drying process in step S5, the wind speed of the hot air circulation drying oven is controlled at 1-3 m / s, and the particles are turned over every 1 hour to ensure uniform drying; After drying, use a rapid moisture meter to test the moisture content of the particles. If the moisture content does not meet the requirements, extend the drying time and adjust the drying temperature.

10. The method for preparing the sodium hyaluronate and chondroitin composite oral supplement according to claim 3, characterized in that: In the quality inspection of step S10, the appearance inspection requires that the tablet surface is smooth, the color is uniform, and there are no obvious spots, cracks, and deformations; The content was determined by high performance liquid chromatography, and the content of sodium hyaluronate and chondroitin should be within the range of 90%-110% of the labeled amount respectively; The disintegration time should not exceed 60 minutes. The microbial limit test must comply with the provisions of the "Chinese Pharmacopoeia". The total number of bacteria shall not exceed 1000 cfu / g, the total number of molds and yeasts shall not exceed 100 cfu / g, and pathogenic bacteria shall not be detected.

Images