Nano-emulsion film flash release tablet containing sialic acid and preparation method of nano-emulsion film flash release tablet

Abstract

The invention provides a sialic acid-containing nanoemulsion diaphragm flash release tablet and a preparation method thereof. The sialic acid-containing nanoemulsion diaphragm flash release tablet is prepared from the following raw materials: a skeleton proppant, an adhesive, a water-based dispersion medium, sialic acid, an emulsifier and liquid grease, and the thickness of the diaphragm flash release sheet is 0.01 to 0.5 mm. According to the technical scheme, sialic acid is added into a water-based dispersion medium and forms a water-in-oil emulsion with an oil phase under the action of an emulsifier, then the water-in-oil emulsion is mixed with the water-based dispersion medium to obtain a nano-emulsion, and finally the nano-emulsion is coated, dried and processed into the flash release tablet. The flashover release tablet can be quickly dissolved in the oral cavity, and the re-dissolved sialic acid enters the human body in the form of nano-emulsion, so that the bioavailability of the sialic acid is improved.

Description

Technical Field

[0001] This invention belongs to the field of health food technology, specifically relating to a nanoemulsion film flash release tablet containing sialic acid and its preparation method. Background Technology

[0002] Microemulsion / nanoemulsion technology has enormous commercial value in the field of nutritional and health products, for example, by forming lyophilized products from fat-soluble substances, plant extracts and other nutrients into nanoemulsions.

[0003] Sialic acid, also known as sialic acid (SA), scientifically named N-acetylneuraminic acid, is a naturally occurring carbohydrate. It was initially isolated from submandibular gland mucin, hence its name. Sialic acid typically exists in the form of oligosaccharides, glycolipids, or glycoproteins. The brain has the highest sialic acid content in the human body. The sialic acid content in the gray matter of the brain is 15 times that of internal organs such as the liver and lungs. The main dietary source of sialic acid is breast milk, and it is also found in cow's milk, eggs, and cheese.

[0004] In medicine, glycolipids containing sialic acid are called gangliosides, which play a crucial role in the formation and development of the brain and nervous system. Animal studies have also shown that decreased ganglioside levels are associated with early malnutrition and reduced learning ability, while sialic acid supplementation can improve learning behavior in animals. Adequate sialic acid supply may be particularly important for the normal brain development of low birth weight infants. After birth, sialic acid in breast milk is essential for ensuring normal development in infants. Studies show that maternal sialic acid levels tend to decline over time after delivery.

[0005] Therefore, maintaining adequate sialic acid intake during and after pregnancy can help maintain sialic acid levels in the body. Furthermore, sialic acid levels are significantly correlated with DHA levels, suggesting that it is highly likely related to the development of the infant's brain structure and function, and both may be beneficial for early brain development.

[0006] There are currently publicly available information on DHA nanoemulsion freeze-drying technology, such as the method for preparing DHA nanoemulsion freeze-dried powder disclosed in Chinese Patent 201610235834.X. The method involves adding DHA algal oil and surfactant sequentially to a centrifuge tube, followed by the addition of an aqueous phase to obtain an emulsion; ultrasonically treating the obtained emulsion to obtain a DHA nanoemulsion aqueous solution; adding a freeze-drying protectant to the obtained DHA nanoemulsion aqueous solution, dissolving it, and then freeze-drying it to obtain DHA nanoemulsion freeze-dried powder.

[0007] However, traditional lyophilized powders or tablets are not suitable for young children, patients with difficulty swallowing, people with difficulty accessing water, or those with mental disorders who resist medication. Orally disintegrating films, a novel drug formulation, typically involve dissolving or dispersing the drug in a film-forming material to create a thin film, but the dissolution time is slightly longer than that of lyophilized flash-release tablets. Based on current technology, no similar flash-release tablet formulations to orally disintegrating films have yet been developed, especially the technology for film-disintegrating flash-release tablets containing nanoemulsions, which has not yet been disclosed. Summary of the Invention

[0008] The purpose of this invention is to provide a nanoemulsion film flash-release tablet containing sialic acid and its preparation method, aiming to solve the technical problem of the lack of efficient and convenient oral dosage forms of sialic acid in the market.

[0009] To achieve the above objectives, the raw materials of the nanoemulsion membrane flash release tablet containing sialic acid proposed in this invention include a skeleton support agent, a binder, an aqueous dispersion medium, sialic acid, an emulsifier, and liquid oil; the thickness of the membrane flash release tablet is 0.01~0.5mm.

[0010] Optionally, by weight percentage, the raw materials of the sialic acid-containing nanoemulsion film flash release tablets include: 10-20 parts of matrix support agent, 0.5-1 part of binder, 0.1-0.5 parts of sialic acid, 5-15 parts of emulsifier, 5-15 parts of liquid oil, and 50-200 parts of aqueous dispersion medium.

[0011] Optionally, the aqueous dispersion medium includes one of water, salt solution, and aqueous solution of short-chain alcohol.

[0012] Optionally, the emulsifier is one of glycerol mono-fatty acid ester, glycerol di-fatty acid ester, and polysorbate.

[0013] Optionally, the liquid oil is either algal oil DHA or fish oil DHA.

[0014] Optionally, the skeletal support agent is one of sugar or polyol.

[0015] Optionally, the sugar is made from one or more of the following: sucrose, lactose, and fructose.

[0016] Optionally, the polyol is made from one or more of mannitol, sorbitol, xylitol, lactitol and erythritol.

[0017] This invention also proposes a method for preparing the above-mentioned nanoemulsion film flash-release tablet containing sialic acid, the preparation method comprising the following steps: S10. Dissolve sialic acid in an aqueous dispersion medium to form the first aqueous phase; S20. The skeleton support agent and binder are dissolved in an aqueous dispersion medium to form a second aqueous phase; S30. Dissolve the emulsifier in liquid grease to form an oil phase; S40. The oil phase and the first aqueous phase are mixed and homogenized to obtain a water-in-oil emulsion; S50. The water-in-oil emulsion and the second aqueous phase are mixed and homogenized to obtain a nanoemulsion; S60. After the nanoemulsion is allowed to stand and degas, it is coated, dried, slit and packaged to obtain film flash release tablets.

[0018] Optionally, in step S60, the drying temperature is 40~60℃.

[0019] In this invention, sialic acid is added to an aqueous dispersion medium, where it forms a water-in-oil emulsion with the oil phase under the action of an emulsifier. This emulsion is then mixed with the aqueous dispersion medium to obtain a nanoemulsion, which is finally processed into a membrane flash-release tablet. This membrane flash-release tablet can dissolve rapidly in the oral cavity, and the reconstituted sialic acid enters the human body through the nanoemulsion, thus improving the bioavailability of sialic acid. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0021] Figure 1 This is a schematic flowchart of an embodiment of the membrane flash release tablet containing sialic acid nanoemulsion provided by the present invention.

[0022] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them.

[0024] It should be noted that, unless specific conditions are specified in the embodiments, conventional conditions or conditions recommended by the manufacturer should be followed. Reagents or instruments whose manufacturers are not specified are all commercially available products. Furthermore, the meaning of "and / or" throughout the text includes three parallel solutions; for example, "A and / or B" includes solution A, solution B, or a solution that simultaneously satisfies A and B. In addition, the technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or impossible to implement, such a combination should be considered non-existent and not within the scope of protection claimed by this invention. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without inventive effort are within the scope of protection of this invention.

[0025] Traditional lyophilized powders or tablets are not suitable for young children, patients with difficulty swallowing, people with difficulty accessing water, or those with mental disorders who resist medication. Orally disintegrating films, a novel drug formulation, typically involve dissolving or dispersing the drug in a film-forming material to create a thin film, but the dissolution time is slightly longer than that of lyophilized flash-release tablets. Based on current technology, no similar flash-release tablet formulation has yet been developed, especially the technology for film-disintegrating flash-release tablets containing nanoemulsions, which has not yet been disclosed.

[0026] In view of this, the present invention provides a sialic acid-containing nanoemulsion membrane flash release tablet and its preparation method. In this embodiment, the sialic acid-containing nanoemulsion membrane flash release tablet prepared comprises, by weight percentage, 10-20 parts of a matrix support agent, 0.5-1 part of a binder, 0.1-0.5 parts of sialic acid, 5-15 parts of an emulsifier, 5-15 parts of liquid oil, and 50-200 parts of an aqueous dispersion medium; the thickness of the membrane flash release tablet is 0.01-0.5 mm.

[0027] The following is combined with Figure 1 A schematic flowchart of an embodiment of the preparation method of a flash release tablet containing sialic acid nanoemulsion film is provided. The preparation method includes the following steps.

[0028] Step S10: Dissolve sialic acid in an aqueous dispersion medium to form the first aqueous phase.

[0029] In practice, sialic acid is dissolved in a 10% to 30% volume aqueous dispersion medium by stirring. The aqueous dispersion medium can be one of water, salt solution, or short-chain alcohol aqueous solution. The salt solution can be physiological saline, and the short-chain alcohol aqueous solution can be a 50% volume methanol aqueous solution or a 75% volume ethanol aqueous solution.

[0030] Step S20: Dissolve the skeleton support agent and adhesive in an aqueous dispersion medium to form a second aqueous phase.

[0031] In specific implementation, the skeleton support agent and the binder are dissolved by stirring in an aqueous dispersion medium of 70% to 90% by volume. The skeleton support agent is selected from sugar and polyol. The sugar can be selected from one or more of sucrose, α-lactose and fructose and mixed together. The polyol can be selected from one or more of mannitol, sorbitol, xylitol, lactitol and erythritol and mixed together. The aqueous dispersion medium is selected from water and salt solution. The salt solution can be physiological saline.

[0032] Step S30: Dissolve the emulsifier in the liquid oil to form an oil phase.

[0033] In practice, the emulsifier is added to the liquid oil and heated to 60-80℃. After the emulsifier is completely dissolved, it is homogenized using a mixer at a speed of 1500-2000 rpm for 10-20 minutes to obtain the oil phase. The emulsifier is selected from one of monoglyceride, diglyceride, and polysorbate, while the liquid oil is selected from one of algal oil DHA and fish oil DHA.

[0034] Step S40: Mix and homogenize the oil phase and the first aqueous phase to obtain a water-in-oil emulsion.

[0035] In practice, the first aqueous phase is heated to 60-80℃ and then slowly added to the oil phase. The temperature of both the first aqueous phase and the oil phase is maintained at 60-80℃. Homogenization is then carried out at a speed of 1500-2000 rpm for 10-20 minutes to obtain a water-in-oil emulsion.

[0036] Step S50: Mix and homogenize the oil-in-water emulsion and the second aqueous phase to obtain a nanoemulsion.

[0037] In practice, the second aqueous phase is heated to 60-80°C, and then the water-in-oil emulsion is slowly added to the second aqueous phase. The temperature of both the second aqueous phase and the water-in-oil emulsion is maintained at 60-80°C. Homogenization is then carried out at a speed of 1500-2000 rpm for 10-20 minutes to obtain a nanoemulsion.

[0038] Step S60: After the nanoemulsion is allowed to stand and degas, it is coated, dried, slit and packaged to obtain film flash release tablets.

[0039] In practice, the nanoemulsion is degassed under vacuum for 10 minutes. Then, the degassed nanoemulsion is sequentially drawn into a coating film or other mold using a peristaltic pump at a rate of 0.1–1 mL / s for coating or pressing. In this embodiment, the moving speed of the coating film is 0.01–0.2 m / s. A doctor blade is used to coat the emulsion into a film with a thickness of 0.01–0.5 mm. The coated film or mold then is pre-frozen in a -80°C freezer for 10–20 minutes. Finally, the pre-frozen blister pack is transferred to a freeze dryer and the following freeze-drying curves are run: -25°C for 90 minutes; -30°C for 100 minutes; -20°C to -10°C for 180 minutes; 25°C for 250 minutes. The sample is then removed and cut to obtain a single-piece flash-release tablet containing 25 mg of sialic acid.

[0040] The process of preparing the sialic acid-containing nanoemulsion membrane flash-release tablets according to the present invention will be further described below, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Example 1

[0041] Formula composition: 100g mannitol 5g gelatin 5g Sialic Acid 50g glycerol monofatty acid ester 50g algal oil DHA 1000mL purified water Preparation process: 5g of sialic acid was dissolved in 100mL of purified water to obtain the first aqueous phase; 100g of mannitol and 5g of gelatin were dissolved in 900mL of purified water to form the second aqueous phase; 50g of glycerol monofatty acid ester was dissolved in 50g of algal oil DHA by heating to form the oil phase; the first aqueous phase was heated to 65℃ and then slowly added to the oil phase at the same temperature, and homogenized at 2000rpm for 10min using a stirrer to obtain a water-in-oil emulsion; the water-in-oil emulsion was kept at 65℃ and slowly added to the second aqueous phase at the same temperature, and homogenized at 2000rpm for 10min using a stirrer to obtain a nanoemulsion; The emulsion was sequentially drawn onto the coating membrane at a rate of 0.25 mL / s using a peristaltic pump. The membrane moved at a speed of 0.1 m / s. A doctor blade was used to coat the liquid into a membrane with a thickness of 0.1 mm. The membrane was pre-frozen in a -80°C freezer for 12 min. The pre-frozen blister pack was then transferred to the freeze dryer and the following freeze-drying curves were run: -25°C for 90 min; -30°C for 100 min; -20°C to -10°C for 180 min; 25°C for 250 min. The sample was then removed and cut into 2.5 cm x 4 cm pieces to obtain a flash-release membrane containing sialic acid nanoemulsion. Example 2

[0042] Formula composition: 100g Mannitol 5g gelatin 5g Sialic Acid 100g of glycerol monofatty acid esters 100g algal oil DHA 1000mL purified water Preparation process: 5g of sialic acid was dissolved in 100mL of purified water to obtain the first aqueous phase; 100g of mannitol and 5g of gelatin were dissolved in 900mL of purified water to form the second aqueous phase; 100g of glycerol monofatty acid ester was dissolved in 100g of algal oil DHA by heating to form the oil phase; the first aqueous phase was heated to 65℃ and then slowly added to the oil phase at the same temperature, and homogenized by stirring at 2000rpm for 10min to obtain a water-in-oil emulsion; the water-in-oil emulsion was kept at 65℃ and slowly added to the second aqueous phase at the same temperature, and homogenized by stirring at 2000rpm for 10min to obtain a nanoemulsion; The emulsion was sequentially pumped onto the coating membrane at a rate of 0.25 mL / s using a peristaltic pump. The membrane moved at a speed of 0.1 m / s. A doctor blade was used to coat the liquid into a membrane with a thickness of 0.1 mm. The membrane was pre-frozen in a -80°C freezer for 12 min. The pre-frozen blister pack was then transferred to the freeze dryer and the following freeze-drying curves were run: -25°C for 90 min; -30°C for 100 min; -20°C to -10°C for 180 min; 25°C for 250 min. The sample was then removed and cut into 2.5 cm x 4 cm pieces to obtain a flash-release membrane containing sialic acid nanoemulsion. Example 3

[0043] Formula composition: 100g mannitol 5g gelatin 5g Sialic Acid 150g glycerol monofatty acid ester 150g algal oil DHA 1000mL purified water Preparation process: 5g of sialic acid was dissolved in 100mL of purified water to obtain the first aqueous phase; 100g of mannitol and 5g of gelatin were dissolved in 900mL of purified water to form the second aqueous phase; 150g of glycerol monofatty acid ester was dissolved in 150g of algal oil DHA by heating to form the oil phase; the first aqueous phase was heated to 65℃ and then slowly added to the oil phase at the same temperature, and homogenized at 2000rpm for 10min using a stirrer to obtain a water-in-oil emulsion; the water-in-oil emulsion was kept at 65℃ and slowly added to the second aqueous phase at the same temperature, and homogenized at 2000rpm for 10min using a stirrer to obtain a nanoemulsion; The emulsion was sequentially pumped onto the coating membrane at a rate of 0.25 mL / s using a peristaltic pump. The membrane moved at a speed of 0.1 m / s. A doctor blade was used to coat the liquid into a membrane with a thickness of 0.1 mm. The membrane was pre-frozen in a -80°C freezer for 12 min. The pre-frozen blister pack was then transferred to the freeze dryer and the following freeze-drying curves were run: -25°C for 90 min; -30°C for 100 min; -20°C to -10°C for 180 min; 25°C for 250 min. The sample was then removed and cut into 2.5 cm x 4 cm pieces to obtain a flash-release membrane containing sialic acid nanoemulsion. Example 4

[0044] Formula composition: 100g α-lactose 5g gelatin 5g Sialic Acid 50g glycerol monofatty acid ester 50g algal oil DHA 1000mL purified water Preparation process: 5g of sialic acid was dissolved in 100mL of purified water to obtain the first aqueous phase; 100g of α-lactose and 5g of gelatin were dissolved in 900mL of purified water to form the second aqueous phase; 50g of glycerol monofatty acid ester was dissolved in 50g of algal oil DHA by heating to form the oil phase; the first aqueous phase was heated to 65℃ and then slowly added to the oil phase at the same temperature, and homogenized at 2000rpm for 10min using a stirrer to obtain a water-in-oil emulsion; the water-in-oil emulsion was kept at 65℃ and slowly added to the second aqueous phase at the same temperature, and homogenized at 2000rpm for 10min using a stirrer to obtain a nanoemulsion; the emulsion was then pumped through a peristaltic pump at a flow rate of 0.25mL / s. The material was sequentially drawn onto the coated membrane at a speed of 0.1 m / s. A doctor blade was used to coat the material into a 0.1 mm thick membrane. The membrane was then pre-frozen in a -80°C freezer for 12 min. The pre-frozen blister pack was then transferred to the freeze dryer and the following freeze-drying curves were run: -25°C for 90 min; -30°C for 100 min; -20°C to -10°C for 180 min; and 25°C for 250 min. The sample was then removed and cut into 2.5 cm x 4 cm pieces to obtain a flash-release membrane containing sialic acid nanoemulsion. Example 5

[0045] Formula composition: 100g erythritol 5g gelatin 5g Sialic Acid 50g glycerol monofatty acid ester 50g algal oil DHA 1000mL purified water Preparation process: 5g of sialic acid was dissolved in 100mL of purified water to obtain the first aqueous phase; 100g of erythritol and 5g of gelatin were dissolved in 900mL of purified water to form the second aqueous phase; 50g of glycerol monofatty acid ester was dissolved in 50g of algal oil DHA by heating to form the oil phase; the first aqueous phase was heated to 65℃ and then slowly added to the oil phase at the same temperature, and homogenized at 2000rpm for 10min using a stirrer to obtain a water-in-oil emulsion; the water-in-oil emulsion was kept at 65℃ and slowly added to the second aqueous phase at the same temperature, and homogenized at 2000rpm for 10min using a stirrer to obtain a nanoemulsion; The emulsion was sequentially drawn onto the coating membrane at a rate of 0.25 mL / s using a peristaltic pump. The membrane moved at a speed of 0.1 m / s. A doctor blade was used to coat the liquid into a membrane with a thickness of 0.1 mm. The membrane was pre-frozen in a -80°C freezer for 12 min. The pre-frozen blister pack was then transferred to the freeze dryer and the following freeze-drying curves were run: -25°C for 90 min; -30°C for 100 min; -20°C to -10°C for 180 min; 25°C for 250 min. The sample was then removed and cut into 2.5 cm x 4 cm pieces to obtain a flash-release membrane containing sialic acid nanoemulsion. Example 6

[0046] Formula composition: 100g xylitol 5g gelatin 5g Sialic Acid 50g glycerol monofatty acid ester 50g algal oil DHA 1000mL purified water Preparation process: 5g of sialic acid was dissolved in 100mL of purified water to obtain the first aqueous phase; 100g of mannitol and 5g of gelatin were dissolved in 900mL of purified water to form the second aqueous phase; 50g of glycerol monofatty acid ester was dissolved in 50g of algal oil DHA by heating to form the oil phase; the first aqueous phase was heated to 65℃ and then slowly added to the oil phase at the same temperature, and homogenized at 2000rpm for 10min using a stirrer to obtain a water-in-oil emulsion; the water-in-oil emulsion was kept at 65℃ and slowly added to the second aqueous phase at the same temperature, and homogenized at 2000rpm for 10min using a stirrer to obtain a nanoemulsion; The emulsion was sequentially drawn onto the coating membrane at a rate of 0.25 mL / s using a peristaltic pump. The membrane moved at a speed of 0.1 m / s. A doctor blade was used to coat the liquid into a membrane with a thickness of 0.1 mm. The membrane was pre-frozen in a -80°C freezer for 12 min. The pre-frozen blister pack was then transferred to the freeze dryer and the following freeze-drying curves were run: -25°C for 90 min; -30°C for 100 min; -20°C to -10°C for 180 min; 25°C for 250 min. The sample was then removed and cut into 2.5 cm x 4 cm pieces to obtain a flash-release membrane containing sialic acid nanoemulsion. Example 7

[0047] Similar to Example 1, the difference is that 100g of mannitol and 5g of gelatin are dissolved in 800mL of purified water to form a second aqueous phase. Example 8

[0048] Similar to Example 1, the difference is that 100g of mannitol and 5g of gelatin are dissolved in 700mL of purified water to form a second aqueous phase. Example 9

[0049] Similar to Example 1, the difference is that 100g of mannitol and 5g of gelatin are dissolved in 600mL of purified water to form a second aqueous phase.

[0050] Comparative Example 1 Formula composition: 100g mannitol 5g Sialic Acid 1000mL purified water Preparation process: 5g of sialic acid was dissolved in 100mL of purified water to obtain the first aqueous phase; 100g of mannitol was dissolved in 900mL of purified water to form the second aqueous phase; the first aqueous phase was added to the second aqueous phase and mixed and homogenized to obtain the material solution; after the material solution was allowed to stand and degassed, it was sequentially drawn onto the coating membrane at a speed of 0.25mL / s using a peristaltic pump, and the moving speed of the coating membrane was 0.1m / s. The material solution was coated into a membrane with a thickness of 0.1mm using a doctor blade; the membrane was pre-frozen in a -80°C freezer for 12min; the pre-frozen blister pack was transferred to the freeze dryer plate and the following freeze-drying curves were run: -25°C for 90min; -30°C for 100min; -20°C to -10°C for 180min; 25°C for 250min. The sample was taken out and cut into 2.5cm x 4cm pieces to obtain the sialic acid nanoemulsion flash release tablets. Sensory evaluation

[0051] Table 1 Sensory Evaluation Table for Candy Film Flash Release Tablets (Maximum score for each item: 20 points)

[0052] Five researchers were randomly selected to evaluate the hardness, texture, and sweetness of the film flash tablets from Examples 1-9 and Comparative Example 1, respectively. The median of the scores for each item of Examples 1-9 and Comparative Example 1 was taken. After observation and tasting by the researchers, the film flash tablets of Examples 1-9 and Comparative Example 1 were evaluated according to the scoring criteria in Table 1. The sensory scores obtained are shown in Tables 2-4.

[0053] Table 2 Comparison of the characteristics of the membrane flash release tablets obtained in this experiment

[0054] Comparing the experimental data of Examples 1-3 with Comparative Example 1, as the proportion of oil phase in the nanoemulsion increases, the hardness of the film flash release tablet decreases and the number of bubbles decreases, but the oral dissolution time increases. It can be seen that excessive increase of oil phase will lead to an increase in nanoparticles, which in turn will increase the number of bubbles generated during freeze-drying and slow down the disintegration rate in the oral cavity.

[0055] Table 3 Comparison of the characteristics of the membrane flash release tablets obtained in this experiment

[0056] Comparing the experimental data of Examples 4-6 with Comparative Example 1, different skeletal support agents showed different hardness and sweetness after freeze-drying.

[0057] Table 4 Comparison of the characteristics of the membrane flash release tablets obtained in this experiment

[0058] Comparing the experimental data of Example 1 with those of Examples 7-9, as the specific gravity of the second water decreases, the pores of the membrane flash release tablet decrease, the oral dissolution time increases, and the hardness increases.

[0059] In this technical solution, the resulting membrane flash-release tablet containing sialic acid nanoemulsion can achieve nanoscale dissolution, dissolve rapidly after sublingual administration, and has a small particle size after reconstitution, making it less prone to aggregation and precipitation, and has a small dispersion coefficient. It can be applied in biomedicine and food.

[0060] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0061] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A nanoemulsion film flash-release tablet containing sialic acid, characterized in that, The raw materials for preparing the sialic acid-containing nanoemulsion membrane flash release tablets include a skeleton support agent, a binder, an aqueous dispersion medium, sialic acid, an emulsifier, and liquid oils; the thickness of the membrane flash release tablets is 0.01~0.5 mm.

2. The nanoemulsion film flash-release tablet containing sialic acid as described in claim 1, characterized in that, The raw materials for preparing the sialic acid-containing nanoemulsion film flash release tablets, by weight percentage, include: 10-20 parts of skeleton support agent, 0.5-1 part of binder, 0.1-0.5 parts of sialic acid, 5-15 parts of emulsifier, 5-15 parts of liquid oil, and 50-200 parts of aqueous dispersion medium.

3. The nanoemulsion film flash-release tablet containing sialic acid as described in claim 1, characterized in that, The aqueous dispersion medium includes one of water, salt solution, and aqueous solution of short-chain alcohol.

4. The nanoemulsion film flash-release tablet containing sialic acid as described in claim 1, characterized in that, The emulsifier is one of glycerol mono-fatty acid ester, glycerol di-fatty acid ester, and polysorbate.

5. The nanoemulsion film flash-release tablet containing sialic acid as described in claim 1, characterized in that, The liquid oil is either algal oil DHA or fish oil DHA.

6. The nanoemulsion film flash-release tablet containing sialic acid as described in claim 1, characterized in that, The skeletal support is one of sugars or polyols.

7. The nanoemulsion film flash-release tablet containing sialic acid as described in claim 6, characterized in that, The sugar is made from one or more of the following: sucrose, lactose, and fructose.

8. The nanoemulsion film flash-release tablet containing sialic acid as described in claim 6, characterized in that, The polyol is prepared by mixing one or more of mannitol, sorbitol, xylitol, lactitol and erythritol.

9. A method for preparing a nanoemulsion film flash-release tablet containing sialic acid as described in any one of claims 1-8, characterized in that, The preparation method includes the following steps: S10. Dissolve sialic acid in an aqueous dispersion medium to form the first aqueous phase; S20. The skeleton support agent and binder are dissolved in an aqueous dispersion medium to form a second aqueous phase; S30. Dissolve the emulsifier in liquid grease to form an oil phase; S40. The oil phase and the first aqueous phase are mixed and homogenized to obtain a water-in-oil emulsion; S50. The water-in-oil emulsion and the second aqueous phase are mixed and homogenized to obtain a nanoemulsion; S60. After the nanoemulsion is allowed to stand and degas, it is coated, dried, slit and packaged to obtain film flash release tablets.

10. The method for preparing the sialic acid-containing nanoemulsion film flash-release tablet as described in claim 9, characterized in that, In step S60, the drying temperature is 40~60℃.

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