Ganoderma lucidum spore powder and dendrobium polysaccharide-containing tablets and preparation method thereof

Abstract

This invention provides a lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide, and its preparation method. By weight, the constituent raw materials include: 15-25 parts of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres, 4-9 parts of fructooligosaccharide-γ-aminobutyric acid graft, 10-16 parts of xylitol, 10-16 parts of erythritol, 5-10 parts of microcrystalline cellulose, 2-4 parts of hydroxypropyl methylcellulose, 1-3 parts of γ-aminobutyric acid, 0.3-0.6 parts of magnesium stearate, and 0.2-0.5 parts of citric acid. This lozenge incorporates pharmaceutical excipient applications. By encapsulating the two polysaccharides in the composite nanospheres and other components, it can prevent oxidation, improve bioavailability, synergistically enhance sleep-aiding effects, mask bitterness to optimize taste, and ensure smooth tablet formation and stable storage and transportation.

Description

Technical Field

[0001] This invention relates to the field of lozenge technology, specifically to a lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method. Background Technology

[0002] Both Ganoderma lucidum spore powder and Dendrobium officinale are natural food and medicine ingredients. Their polysaccharides, triterpenoids, and other active components offer various health benefits, including boosting immunity, combating fatigue, and regulating sleep, making them widely used in the health product industry. With the development of the bio-health industry, advancements in pharmaceutical excipient and packaging material manufacturing technologies have laid the foundation for the development of products containing these active ingredients. The number of related health products on the market is gradually increasing, but most are presented in the form of single raw materials or simple compound formulations.

[0003] Existing polysaccharide lozenges often suffer from problems such as easy oxidation and inactivation of active ingredients, low bioavailability, and some products fail to meet consumer needs and storage and transportation requirements due to their bitter taste and insufficient molding stability. Therefore, optimizing the taste and improving the molding and storage performance of lozenges while ensuring the activity stability and bioavailability of Ganoderma lucidum spore powder polysaccharides and Dendrobium officinale polysaccharides has become an urgent technical problem to be solved in the current preparation of related health care lozenges. Summary of the Invention

[0004] To address the problems existing in the prior art, the present invention provides a lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method, so as to obtain a lozenge with good sleep-aiding effect, good taste, stable tablets and easy transportation.

[0005] To achieve the above objectives, the present invention provides the following technical solution: This application discloses a lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide. By weight, its constituent raw materials include: 15-25 parts of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres, 4-9 parts of fructooligosaccharide-γ-aminobutyric acid graft, 10-16 parts of xylitol, 10-16 parts of erythritol, 5-10 parts of microcrystalline cellulose, 2-4 parts of hydroxypropyl methylcellulose, 1-3 parts of γ-aminobutyric acid, 0.3-0.6 parts of magnesium stearate, and 0.2-0.5 parts of citric acid.

[0006] By implementing the above technical solutions, Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres can encapsulate Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide, reducing the risk of oxidative inactivation of the two polysaccharides, improving their bioavailability in vivo, and ensuring the core active value of the lozenges; the fructooligosaccharide-γ-aminobutyric acid graft can protect γ-aminobutyric acid from degradation by gastric acid, and synergistically enhance the sleep-aiding effect of the lozenges with γ-aminobutyric acid; xylitol and erythritol can mask the slightly bitter taste of the two polysaccharides, optimizing the content... To improve the palatability and user experience, microcrystalline cellulose acts as a filler to ensure tablet formation and acts as a disintegrant to regulate the disintegration rate of the lozenges, meeting the needs of lozenge consumption. Hydroxypropyl methylcellulose can enhance the hardness of the lozenges and reduce the probability of breakage during transportation and storage. Magnesium stearate can reduce friction between the material and the tableting die, preventing sticking and ensuring smooth tableting. Citric acid can regulate oral pH, improve the solubility of disaccharides, and neutralize the sweetness, further improving the palatability of the lozenges.

[0007] Preferably, the raw materials of the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres, by weight, include: 20-30 parts of broken-cell wall Ganoderma lucidum spore powder, 20-30 parts of Dendrobium officinale ultrafine powder, 3.2-7.2 parts of sodium alginate, 0.4-1.2 parts of chitosan, and 2-4.8 parts of calcium chloride.

[0008] By setting up the above technical solution, broken Ganoderma lucidum spore powder can provide Ganoderma lucidum spore powder polysaccharides, and Dendrobium officinale ultrafine powder can provide Dendrobium officinale polysaccharides. The two provide the basis for the activity of dual polysaccharides for composite nanospheres. Sodium alginate and chitosan, as encapsulation carriers, can construct a structure that encapsulates dual polysaccharides. Calcium chloride can assist in the solidification and shaping of this structure, together forming Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres. This achieves physical protection of dual polysaccharides, reduces the probability of oxidative inactivation of dual polysaccharides, and facilitates the slow release of dual polysaccharides in the intestine, thereby improving bioavailability.

[0009] Preferably, the preparation method of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres includes the following steps: 1) Weigh out the broken-cell wall Ganoderma lucidum spore powder and place it in a constant temperature and humidity chamber at 35-40℃ and 70%-80% humidity for 12-24 hours to activate it; weigh out the Dendrobium officinale ultrafine powder and place it in a forced-air drying oven at 75-85℃ for 8-12 hours to dry it. 2) Take the activated and broken-cell wall Ganoderma lucidum spore powder, add 12-18 times the weight of the broken-cell wall Ganoderma lucidum spore powder in purified water, and then transfer it to a high-speed shearing machine. Extract for 8-12 minutes at a shearing speed of 10000-14000 r / min and a water bath temperature of 90-100℃. Filter the extract through a 0.20-0.22μm filter membrane to obtain Ganoderma lucidum spore powder polysaccharide extract. Take the dried Dendrobium officinale ultrafine powder and repeat the above extraction steps to obtain Dendrobium officinale polysaccharide extract. 3) After mixing the Ganoderma lucidum spore powder polysaccharide extract and the Dendrobium officinale polysaccharide extract evenly, add sodium alginate and chitosan, transfer to an ultrasonic reactor, stir at 350-450 r / min for 25-35 min, and then sonicate for 8-12 min at a frequency of 35-45 kHz and a power of 200-300 W to obtain a nano-mixture. 4) Weigh calcium chloride, add 20-30 times the mass of purified water to prepare a calcium chloride solution, and place it in a constant temperature reaction tank at 32-38℃; 5) Pass the nano-mixture through a microfluidic chip with a diameter of 45-50 μm and drop it into a calcium chloride solution at a flow rate of 2-4 mL / h. Solidify at a constant temperature for 20-30 min to obtain white suspended Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres. Then wash the composite nanospheres with purified water 3-4 times, and centrifuge at 3000-4000 r / min for 5-8 min after each wash. Place the purified composite nanospheres in a vacuum freeze dryer and pre-freeze at -45℃ to -35℃ for 1.5-2.5 h. Freeze-dry at a sublimation temperature of 30-40℃ and a vacuum degree of 1-10 Pa for 12-16 h. Pulverize and pass through a 100-120 mesh sieve to obtain the final product.

[0010] By setting up the above technical solutions, the activation treatment of broken-cell Ganoderma lucidum spore powder and the drying treatment of Dendrobium officinale ultrafine powder can lay the foundation for the subsequent efficient extraction of polysaccharides. High-speed shear extraction combined with membrane filtration can quickly obtain high-purity Ganoderma lucidum spore powder polysaccharide extract and Dendrobium officinale polysaccharide extract. After stirring and ultrasonic treatment under specific conditions, the polysaccharides can be fully integrated with sodium alginate and chitosan to form a nanoscale dispersion system, ensuring uniform microsphere particle size. With the help of microfluidic chip precise drop addition and calcium chloride constant temperature solidification, a stable composite nanosphere structure can be constructed. Through washing, centrifugal purification, vacuum freeze drying (avoiding high temperature damage to polysaccharide activity) and pulverization and sieving, high-purity Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres with uniform particle size and good activity retention are finally obtained. These microspheres can effectively encapsulate the two polysaccharides, reduce their oxidative inactivation, and facilitate slow release in subsequent applications.

[0011] Preferably, in step 2), the polysaccharide content of the Ganoderma lucidum spore powder polysaccharide extract is 18%-22%, and the polysaccharide content of the Dendrobium officinale polysaccharide extract is 15%-18%.

[0012] By setting up the above technical solution, the sufficient content and stable concentration of active polysaccharides in the two extracts can be guaranteed. This lays the foundation for the subsequent synergistic formation of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres with sodium alginate and chitosan after the two are mixed. This ensures that the microspheres effectively encapsulate the two polysaccharides, thereby guaranteeing the stability and subsequent release effect of the two polysaccharides and providing core active ingredient support for the high bioavailability of the tablets.

[0013] Preferably, in step 5), the constant temperature curing temperature is 32-38℃.

[0014] By setting up the above technical solution, the cross-linking reaction between sodium alginate, chitosan and calcium chloride can be promoted fully and gently, ensuring that the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres form a stable and uniform coating structure, effectively guaranteeing the encapsulation effect of the polysaccharides, avoiding the situation where the microsphere structure becomes dense due to excessively high temperature or the solidification is incomplete due to excessively low temperature, providing stable physical protection for the polysaccharides, and ensuring that the microspheres can achieve slow intestinal release and high bioavailability.

[0015] Preferably, the raw materials for the fructooligosaccharide-γ-aminobutyric acid graft by weight include: 28-32 parts of fructooligosaccharide, 9-11 parts of γ-aminobutyric acid, 0.04-0.14 parts of citric acid, and appropriate amounts of purified water and anhydrous ethanol.

[0016] By setting up the above technical solution, the fructooligosaccharides in the fructooligosaccharide-γ-aminobutyric acid graft can regulate the intestinal flora and promote the production of short-chain fatty acids. The short-chain fatty acids act on the central nervous system through blood circulation, forming a synergistic regulation of the intestinal-central nervous system with γ-aminobutyric acid and Ganoderma lucidum spore powder polysaccharides, which significantly improves the sleep-aiding effect.

[0017] Preferably, the degree of polymerization of the fructooligosaccharide is 3-5; the mass ratio of purified water to the total mass of fructooligosaccharide and γ-aminobutyric acid is 1.2-1.5:1, and the volume ratio of anhydrous ethanol to purified water is 2.5-3.5:1.

[0018] By setting the above technical solution, the degree of polymerization of fructooligosaccharides is 3-5, which is conducive to its chemical grafting reaction with γ-aminobutyric acid (GABA) and can maintain the regulatory activity of intestinal flora. The mass ratio of purified water to fructooligosaccharides and GABA is controlled within an appropriate range to ensure that the three are fully dissolved and provide a stable medium for the grafting reaction. The volume ratio of anhydrous ethanol to purified water is limited to efficiently precipitate and separate the fructooligosaccharide-γ-aminobutyric acid graft and remove impurities, ultimately obtaining a high-purity, functionally stable graft, ensuring its protective effect on GABA and its synergistic sleep-aiding effect.

[0019] Preferably, the preparation method of the fructooligosaccharide-γ-aminobutyric acid graft includes the following steps: a. Take the oligofructose and dry it in a vacuum drying oven at 60-70℃ for 2-3 hours; take the γ-aminobutyric acid and dry it in a vacuum drying oven at 60-70℃ for 1-2 hours. b. Add the dried fructooligosaccharides and γ-aminobutyric acid to a stainless steel reactor, then add purified water and stir at 200-300 r / min until completely dissolved. Add citric acid, then purge the reactor with nitrogen at a flow rate of 100-200 mL / min to replace the air. Repeat this process three times. Then raise the temperature to 65-75℃ and react at a constant temperature for 2.5-4 h (monitor the pH of the system with a pH meter during the reaction and maintain the pH of the system at 3.5-4.5). c. After the reaction is complete, cool to 20-25℃, add anhydrous ethanol, stir well, and let stand for 1.5-2.5h. Then centrifuge at 3000-4000r / min for 8-12min to collect the precipitate of fructooligosaccharide-γ-aminobutyric acid graft. Wash the precipitate with anhydrous ethanol 2-3 times, centrifuging for 5-8min after each wash. Finally, place the precipitate in a vacuum drying oven at 55-65℃ and 1-10Pa vacuum degree to dry for 8-10h, pulverize and pass through a 100-120 mesh sieve to obtain the fructooligosaccharide-γ-aminobutyric acid graft.

[0020] By setting up the above technical solution, the drying treatment of fructooligosaccharides and γ-aminobutyric acid can remove moisture and impurities, nitrogen replacement can isolate air and avoid oxidation interference, and under suitable temperature and pH conditions, the two can fully undergo grafting reaction. After precipitation with anhydrous ethanol, washing and vacuum drying purification treatment, a high-purity and structurally stable fructooligosaccharide-γ-aminobutyric acid graft product is finally obtained, which can effectively protect γ-aminobutyric acid from gastric acid degradation and work synergistically with intestinal flora regulation to enhance sleep-aiding effects.

[0021] This application also discloses a method for preparing lozenges containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide, comprising the following steps: S1. Place the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres and fructooligosaccharide-γ-aminobutyric acid graft material in a three-dimensional mixer and mix at 15-25 r / min for 15-25 min. Then add xylitol, erythritol, microcrystalline cellulose, hydroxypropyl methylcellulose, γ-aminobutyric acid, and citric acid, and continue mixing for 10-15 min. Finally, add magnesium stearate and mix at 50-100 r / min for 5-8 min. S2. The mixture obtained in S1 is processed using a rotary tablet press. The tablets are compressed under a compression pressure of 6-10 MPa and a compression speed of 40-60 tablets / min to obtain tablets containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide.

[0022] By setting up the above technical solution, the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres, fructooligosaccharide-γ-aminobutyric acid grafted material and various excipients are uniformly dispersed. Magnesium stearate is mixed at high speed to fully exert its lubricating effect and avoid sticking to the mold during tableting. Then, the tablets are compressed by a rotary tableting machine under appropriate pressure and speed, so that the tablets are formed with a uniform structure and moderate hardness. This not only ensures the physical stability of the tablets to withstand storage and transportation, but also facilitates reasonable disintegration and release of effective ingredients in the oral cavity. Finally, a lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide is obtained with uniform component distribution, stable performance and diverse functions.

[0023] Preferably, the tablets weigh 0.5-0.8g and have a thickness of 2.5-4.5mm.

[0024] By setting the above technical solution and limiting the tablet weight, the appropriate loading amount of core active ingredients such as Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres and fructooligosaccharide-γ-aminobutyric acid grafted products can be ensured to meet the efficacy requirements during use; the thickness is set at 2.5-4.5mm, which can not only ensure that the tablets have sufficient physical hardness to withstand storage and transportation in conjunction with the tableting process, but also avoid improper thickness from affecting the disintegration rate and dissolution efficiency when taken orally.

[0025] The beneficial effects of this invention are as follows: The Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres can encapsulate both Ganoderma lucidum spore powder polysaccharides and Dendrobium officinale polysaccharides, reducing the risk of oxidative inactivation of the two polysaccharides, improving their bioavailability in vivo, and ensuring the core active value of the lozenges. The fructooligosaccharide-γ-aminobutyric acid graft can protect γ-aminobutyric acid from degradation by gastric acid and synergistically enhance the sleep-aiding effect of the lozenges with γ-aminobutyric acid. Xylitol and erythritol can mask the slightly bitter taste of the two polysaccharides, optimizing the taste of the lozenges to enhance their overall flavor. User experience: Microcrystalline cellulose, as a filler, ensures tablet formation while acting as a disintegrant to regulate the disintegration rate of the lozenges, meeting the user's needs; Hydroxypropyl methylcellulose enhances the hardness of the lozenges, reducing the probability of breakage during transportation and storage; Magnesium stearate reduces friction between the material and the tableting die, preventing sticking and ensuring smooth tableting; Citric acid regulates oral pH, improves the solubility of disaccharides, and neutralizes sweetness, further improving the taste of the lozenges.

[0026] Ganoderma lucidum spore powder provides polysaccharides from Ganoderma lucidum spore powder, and Dendrobium officinale ultrafine powder provides polysaccharides from Dendrobium officinale. The two provide the basis for the activity of the polysaccharides in the composite nanospheres. Sodium alginate and chitosan serve as encapsulation carriers to construct a structure that encapsulates the polysaccharides. Calcium chloride can assist in the solidification and shaping of this structure, together forming Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres. This achieves physical protection of the polysaccharides, reduces the probability of oxidative inactivation of the polysaccharides, and facilitates the slow release of the polysaccharides in the intestine, thereby improving bioavailability. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] Example 1: This embodiment discloses a lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide. By weight, its constituent raw materials include: 15 parts of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres, 4 parts of fructooligosaccharide-γ-aminobutyric acid graft, 10 parts of xylitol, 10 parts of erythritol, 5 parts of microcrystalline cellulose, 2 parts of hydroxypropyl methylcellulose, 1 part of γ-aminobutyric acid, 0.3 parts of magnesium stearate, and 0.2 parts of citric acid.

[0029] By weight, the raw materials of the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres include: 20 parts of broken Ganoderma lucidum spore powder, 20 parts of Dendrobium officinale ultrafine powder, 3.2 parts of sodium alginate, 0.4 parts of chitosan, and 2 parts of calcium chloride.

[0030] The preparation method of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres includes the following steps: 1) Weigh out the broken-cell wall Ganoderma lucidum spore powder and activate it in a constant temperature and humidity chamber at 35-40℃ and 70% humidity for 12 hours; weigh out the Dendrobium officinale ultrafine powder and dry it in a forced-air drying oven at 75℃ for 8 hours. 2) Take the activated and broken-cell wall Ganoderma lucidum spore powder, add 12 times the mass of purified water, and then transfer it to a high-speed shearing machine. Extract for 8 minutes at a shearing speed of 10000 r / min and a water bath temperature of 90℃. Filter the extract through a 0.20 μm filter membrane to obtain a Ganoderma lucidum spore powder polysaccharide extract with a polysaccharide mass fraction of 18%. Take the dried Dendrobium officinale ultrafine powder and repeat the above extraction steps to obtain a Dendrobium officinale polysaccharide extract with a polysaccharide mass fraction of 15%. 3) After mixing the Ganoderma lucidum spore powder polysaccharide extract and the Dendrobium officinale polysaccharide extract evenly, add sodium alginate and chitosan, transfer to an ultrasonic reactor, stir at 350 r / min for 25 min, and then sonicate for 8 min at a frequency of 35 kHz and a power of 200 W to obtain a nano mixture. 4) Weigh calcium chloride, add 20 times the mass of purified water to prepare a calcium chloride solution, and place it in a constant temperature reaction tank at 32℃; 5) The nano-mixture was passed through a 45 μm diameter microfluidic chip and dripped into a calcium chloride solution at a flow rate of 2 mL / h. The mixture was then fixed at 32 °C for 20 min to obtain white suspended Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres. The composite nanospheres were then washed three times with purified water, and centrifuged at 3000 r / min for 5 min after each wash. The purified composite nanospheres were then placed in a vacuum freeze dryer, pre-frozen at -45 °C for 1.5 h, freeze-dried at a sublimation temperature of 30 °C and a vacuum of 1 Pa for 12 h, and finally pulverized through a 100-mesh sieve to obtain the final product.

[0031] The oligofructose-γ-aminobutyric acid graft polymer, by weight, comprises: 28 parts of oligofructose with a degree of polymerization of 3, 9 parts of γ-aminobutyric acid, 0.04 parts of citric acid, and appropriate amounts of purified water and anhydrous ethanol. The ratio of purified water to the total mass of oligofructose and γ-aminobutyric acid is 1.2:1, and the ratio of anhydrous ethanol to purified water is 2.5:1.

[0032] The preparation method of fructooligosaccharide-γ-aminobutyric acid grafts includes the following steps: a. Take the oligofructose and dry it in a vacuum drying oven at 60℃ for 2 hours; take the γ-aminobutyric acid and dry it in a vacuum drying oven at 60℃ for 1 hour. b. Add the dried fructooligosaccharides and γ-aminobutyric acid to a stainless steel reactor, then add purified water and stir at 200 r / min until completely dissolved. Add citric acid, then purge the air in the reactor with nitrogen at a flow rate of 100 mL / min. Repeat this process 3 times. Then raise the temperature to 65℃ and keep the reaction at a constant temperature for 2.5 h (monitor the pH of the system with a pH meter during the reaction and maintain the pH of the system at 3.5). c. After the reaction is complete, cool to 20°C, add anhydrous ethanol, stir well and let stand for 1.5 h, then centrifuge at 3000 r / min for 8 min to collect the precipitate of fructooligosaccharide-γ-aminobutyric acid graft. The precipitate is then washed twice with anhydrous ethanol, centrifuged for 5 min after each wash, and finally placed in a vacuum drying oven at 55°C and 1 Pa vacuum degree to dry for 8 h. The precipitate is then pulverized and passed through a 100-mesh sieve to obtain the fructooligosaccharide-γ-aminobutyric acid graft.

[0033] This embodiment also discloses a method for preparing lozenges containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide, comprising the following steps: S1. Place the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres and fructooligosaccharide-γ-aminobutyric acid graft material in a three-dimensional mixer and mix at 15 r / min for 15 min. Then add xylitol, erythritol, microcrystalline cellulose, hydroxypropyl methylcellulose, γ-aminobutyric acid and citric acid, and continue mixing for 10 min. Finally, add magnesium stearate and mix at 50 r / min for 5 min. S2. The mixture obtained in S1 was processed using a rotary tablet press. The tablets were compressed at a pressure of 6 MPa and a speed of 40 tablets / min to obtain tablets containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide. The tablet weight was 0.5 g and the thickness was 2.5 mm.

[0034] Example 2: This embodiment discloses a lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide. By weight, its constituent raw materials include: 25 parts of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres, 9 parts of fructooligosaccharide-γ-aminobutyric acid graft, 16 parts of xylitol, 16 parts of erythritol, 10 parts of microcrystalline cellulose, 4 parts of hydroxypropyl methylcellulose, 3 parts of γ-aminobutyric acid, 0.6 parts of magnesium stearate, and 0.5 parts of citric acid.

[0035] By weight, the raw materials of the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres include: 30 parts of broken Ganoderma lucidum spore powder, 30 parts of Dendrobium officinale ultrafine powder, 7.2 parts of sodium alginate, 1.2 parts of chitosan, and 4.8 parts of calcium chloride.

[0036] The preparation method of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres includes the following steps: 1) Weigh out the broken-cell wall Ganoderma lucidum spore powder and place it in a constant temperature and humidity chamber at 40℃ and 80% humidity for 24 hours to activate it; weigh out the Dendrobium officinale ultrafine powder and place it in a forced-air drying oven at 85℃ for 12 hours to dry it. 2) Take the activated and broken-cell wall Ganoderma lucidum spore powder, add 18 times the mass of purified water, and then transfer it to a high-speed shearing machine. Extract for 12 minutes at a shearing speed of 14000 r / min and a water bath temperature of 100℃. Filter the extract through a 0.22 μm filter membrane to obtain a Ganoderma lucidum spore powder polysaccharide extract with a polysaccharide mass fraction of 22%. Take the dried Dendrobium officinale ultrafine powder and repeat the above extraction steps to obtain a Dendrobium officinale polysaccharide extract with a polysaccharide mass fraction of 18%. 3) After mixing the Ganoderma lucidum spore powder polysaccharide extract and the Dendrobium officinale polysaccharide extract evenly, add sodium alginate and chitosan, transfer to an ultrasonic reactor, stir at 450 r / min for 35 min, and then sonicate for 12 min at a frequency of 45 kHz and a power of 300 W to obtain a nano mixture. 4) Weigh calcium chloride, add 30 times the mass of purified water to prepare a calcium chloride solution, and place it in a constant temperature reaction tank at 38℃; 5) The nano-mixture was passed through a 50 μm diameter microfluidic chip and dripped into a calcium chloride solution at a flow rate of 4 mL / h. The mixture was then fixed at 38 °C for 30 min to obtain white suspended Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres. The composite nanospheres were then washed four times with purified water, and centrifuged at 4000 r / min for 8 min after each wash. The purified composite nanospheres were then placed in a vacuum freeze dryer, pre-frozen at -35 °C for 2.5 h, freeze-dried at a sublimation temperature of 40 °C and a vacuum of 10 Pa for 16 h, and finally pulverized through a 120 mesh sieve to obtain the final product.

[0037] The oligofructose-γ-aminobutyric acid graft polymer, by weight, comprises: 32 parts of oligofructose with a degree of polymerization of 5, 11 parts of γ-aminobutyric acid, 0.14 parts of citric acid, and appropriate amounts of purified water and anhydrous ethanol. The ratio of purified water to the total mass of oligofructose and γ-aminobutyric acid is 1.5:1, and the ratio of anhydrous ethanol to purified water is 3.5:1.

[0038] The preparation method of fructooligosaccharide-γ-aminobutyric acid grafts includes the following steps: a. Take the oligofructose and dry it in a vacuum drying oven at 70℃ for 3 hours; take the γ-aminobutyric acid and dry it in a vacuum drying oven at 70℃ for 2 hours. b. Add the dried fructooligosaccharides and γ-aminobutyric acid to a stainless steel reactor, then add purified water and stir at 300 r / min until completely dissolved. Add citric acid, then purge the air in the reactor with nitrogen at a flow rate of 200 mL / min. Repeat this process 3 times. Then raise the temperature to 75℃ and react at a constant temperature for 4 h (monitor the pH of the system with a pH meter during the reaction and maintain the pH of the system at 4.5). c. After the reaction is complete, cool to 25°C, add anhydrous ethanol, stir well and let stand for 2.5 h, then centrifuge at 4000 r / min for 12 min to collect the precipitate of fructooligosaccharide-γ-aminobutyric acid graft. The precipitate is then washed three times with anhydrous ethanol, centrifuged for 8 min after each wash, and finally placed in a vacuum drying oven at 65°C and 10 Pa vacuum degree to dry for 10 h. The precipitate is then pulverized and passed through a 120 mesh sieve to obtain the fructooligosaccharide-γ-aminobutyric acid graft.

[0039] This embodiment also discloses a method for preparing lozenges containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide, comprising the following steps: S1. Place the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres and fructooligosaccharide-γ-aminobutyric acid graft material in a three-dimensional mixer and mix at 25 r / min for 25 min. Then add xylitol, erythritol, microcrystalline cellulose, hydroxypropyl methylcellulose, γ-aminobutyric acid and citric acid, and continue mixing for 15 min. Finally, add magnesium stearate and mix at 100 r / min for 8 min. S2. The mixture obtained in S1 was processed using a rotary tablet press. The tablets were compressed at a pressure of 10 MPa and a speed of 60 tablets / min to obtain tablets containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide. The tablet weight was 0.8 g and the thickness was 4.5 mm.

[0040] Example 3: This embodiment discloses a lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide. By weight, its constituent raw materials include: 20 parts of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres, 6 parts of fructooligosaccharide-γ-aminobutyric acid graft, 13 parts of xylitol, 13 parts of erythritol, 7 parts of microcrystalline cellulose, 3 parts of hydroxypropyl methylcellulose, 2 parts of γ-aminobutyric acid, 0.4 parts of magnesium stearate, and 0.4 parts of citric acid.

[0041] By weight, the raw materials of the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres include: 25 parts of broken Ganoderma lucidum spore powder, 25 parts of Dendrobium officinale ultrafine powder, 5.2 parts of sodium alginate, 0.8 parts of chitosan, and 3.2 parts of calcium chloride.

[0042] The preparation method of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres includes the following steps: 1) Weigh out the broken-cell wall Ganoderma lucidum spore powder and place it in a constant temperature and humidity chamber at 36℃ and 75% humidity for 18 hours to activate it; weigh out the Dendrobium officinale ultrafine powder and place it in a forced-air drying oven at 80℃ for 10 hours to dry it. 2) Take the activated and broken-cell wall Ganoderma lucidum spore powder, add 15 times the mass of purified water, and then transfer it to a high-speed shearing machine. Extract for 10 minutes at a shearing speed of 12000 r / min and a water bath temperature of 95℃. Filter the extract through a 0.21 μm filter membrane to obtain a Ganoderma lucidum spore powder polysaccharide extract with a polysaccharide mass fraction of 20%. Take the dried Dendrobium officinale ultrafine powder and repeat the above extraction steps to obtain a Dendrobium officinale polysaccharide extract with a polysaccharide mass fraction of 16%. 3) After mixing the Ganoderma lucidum spore powder polysaccharide extract and the Dendrobium officinale polysaccharide extract evenly, add sodium alginate and chitosan, transfer to an ultrasonic reactor, stir at 400 r / min for 30 min, and then sonicate for 10 min at a frequency of 40 kHz and a power of 250 W to obtain a nano-mixture. 4) Weigh calcium chloride and add 25 times the mass of purified water to prepare a calcium chloride solution, and place it in a constant temperature reaction tank at 35℃. 5) The nano-mixture was passed through a 47 μm diameter microfluidic chip and dripped into a calcium chloride solution at a flow rate of 3 mL / h. The mixture was then fixed at 35 °C for 25 min to obtain white suspended Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres. The composite nanospheres were then washed three times with purified water, and centrifuged at 3500 r / min for 6 min after each wash. The purified composite nanospheres were then placed in a vacuum freeze dryer, pre-frozen at -40 °C for 2 h, and freeze-dried at a sublimation temperature of 35 °C and a vacuum of 5 Pa for 14 h. The nanospheres were then pulverized and passed through a 110 mesh sieve to obtain the final product.

[0043] The oligofructose-γ-aminobutyric acid graft polymer, by weight, comprises: 30 parts of oligofructose with a degree of polymerization of 4, 10 parts of γ-aminobutyric acid, 0.09 parts of citric acid, and appropriate amounts of purified water and anhydrous ethanol. The ratio of purified water to the total mass of oligofructose and γ-aminobutyric acid is 1.3:1, and the ratio of anhydrous ethanol to purified water is 3:1.

[0044] The preparation method of fructooligosaccharide-γ-aminobutyric acid grafts includes the following steps: a. Take the oligofructose and dry it in a vacuum drying oven at 65℃ for 2.5h; take the γ-aminobutyric acid and dry it in a vacuum drying oven at 65℃ for 1.5h. b. Add the dried fructooligosaccharides and γ-aminobutyric acid to a stainless steel reactor, then add purified water and stir at 250 r / min until completely dissolved. Add citric acid, and then purge the air in the reactor with nitrogen at a flow rate of 150 mL / min. Repeat this process 3 times. Then raise the temperature to 70℃ and keep the reaction at a constant temperature for 3 hours (monitor the pH of the system with a pH meter during the reaction and maintain the pH of the system at 4.0). c. After the reaction is complete, cool to 22°C, add anhydrous ethanol, stir well and let stand for 2 hours, then centrifuge at 3500 r / min for 10 min to collect the precipitate of oligofructose-γ-aminobutyric acid graft. The precipitate is then washed three times with anhydrous ethanol, centrifuged for 6 min after each wash, and finally placed in a vacuum drying oven at 60°C and 6 Pa vacuum degree to dry for 9 hours. The precipitate is then pulverized and passed through a 110 mesh sieve to obtain the oligofructose-γ-aminobutyric acid graft.

[0045] This embodiment also discloses a method for preparing lozenges containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide, comprising the following steps: S1. Place the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres and fructooligosaccharide-γ-aminobutyric acid graft material in a three-dimensional mixer and mix at 20 r / min for 20 min. Then add xylitol, erythritol, microcrystalline cellulose, hydroxypropyl methylcellulose, γ-aminobutyric acid and citric acid, and continue mixing for 12 min. Finally, add magnesium stearate and mix at 75 r / min for 6 min. S2. The mixture obtained in S1 was processed using a rotary tablet press. The tablets were compressed at a pressure of 8 MPa and a speed of 50 tablets / min to obtain tablets containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide. The tablet weight was 0.6 g and the thickness was 3.5 mm.

[0046] Comparative Example 1: A lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method are disclosed. The only difference between this lozenge and Example 3 is that the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres are replaced with microcrystalline cellulose in equal amounts.

[0047] Comparative Example 2: A lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method are disclosed. The only difference between this lozenge and Example 3 is that the oligofructose-γ-aminobutyric acid graft is replaced with γ-aminobutyric acid in equal amounts.

[0048] Comparative Example 3: A lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method are disclosed. The only difference between this lozenge and Example 3 is that the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres were not subjected to ultrasonic treatment (only stirring) during preparation.

[0049] Comparative Example 4: A lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method are disclosed. The only difference between this lozenge and Example 3 is that the drying method of the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres is changed to spray drying (inlet temperature 170℃-190℃).

[0050] Comparative Example 5: A lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method are disclosed. The only difference between this lozenge and Example 3 is that xylitol is replaced with erythritol in equal amounts.

[0051] Comparative Example 6: A lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method are disclosed. The only difference between this lozenge and Example 3 is that microcrystalline cellulose is replaced with an equal amount of hydroxypropyl methylcellulose.

[0052] Comparative Example 7: A lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method are disclosed. The only difference between this lozenge and Example 3 is that the tableting pressure is changed to 4 MPa (lower than the 6-10 MPa range of this method).

[0053] Comparative Example 8: A lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method are described. The only difference between this lozenge and Example 3 is that citric acid is not added.

[0054] Comparative Example 9: A lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide and its preparation method are disclosed. The only difference between this lozenge and Example 3 is that no oligofructose is added to the oligofructose-γ-aminobutyric acid graft.

[0055] The lozenges obtained in Examples 1-3 and Comparative Examples 1-9 were tested for polysaccharide retention rate, in vitro dissolution rate at 15 min, tablet hardness, disintegration time, taste score, sleep improvement rate, and accelerated stability. The testing methods and standards are as follows: 1. Polysaccharide retention rate determination The phenol-sulfuric acid method was used: A 5% phenol solution (5g phenol dissolved in 95mL purified water) and a 0.1mg / mL glucose standard solution (glucose purity ≥99%) were prepared. 0.2, 0.4, 0.6, 0.8, and 1.0mL of the glucose standard solution were placed in test tubes, purified water was added to a final volume of 2mL, 1mL of 5% phenol solution was added, and the mixture was shaken well. 5mL of concentrated sulfuric acid (analytical grade) was quickly added, and the mixture was shaken well. The mixture was then boiled in a water bath for 15 minutes, cooled to room temperature, and the absorbance was measured at 490nm. A standard curve (R0) was plotted. 2 ≥0.999); take 0.1g of lozenges, grind them into powder, add 10mL of purified water, extract in an 80℃ water bath for 1h, filter, take 1mL of filtrate, measure absorbance according to the standard curve procedure, and calculate polysaccharide content; polysaccharide retention rate (%) = (measured polysaccharide content / theoretical polysaccharide content) × 100%.

[0056] 2. In vitro dissolution rate determination at 15 min According to the Chinese Pharmacopoeia 2020 edition, Part IV, General Chapter 0931, the dissolution method was as follows: Artificial saliva at pH 6.8 (formulation: 0.2g potassium dihydrogen phosphate, 0.71g disodium hydrogen phosphate, 0.7g sodium chloride, and purified water to 1000mL) was used as the dissolution medium; a dissolution apparatus was used, with a rotation speed of 50r / min and a temperature of 37±0.5℃; 6 tablets were placed in the dissolution vessel, and 5mL of sample was taken after 15 minutes. The sample was filtered through a 0.22μm filter membrane, and the polysaccharide content of the filtrate was measured; the dissolution rate (%) at 15 minutes was calculated as (polysaccharide amount dissolved at 15 minutes / total polysaccharide amount of the tablets) × 100%.

[0057] 3. Tablet hardness test According to the 2020 edition of the Chinese Pharmacopoeia, Part IV, General Chapter 0922: Using a tablet hardness tester, take 10 tablets, place them one by one in the fixture, and slowly apply pressure until the tablet breaks. Record the pressure value at the time of breakage, and take the average pressure of the 10 tablets as the tablet hardness (unit: N).

[0058] 4. Disintegration time determination According to the 2020 edition of the Chinese Pharmacopoeia, Part IV, General Chapter 0921: A disintegration apparatus was used with artificial saliva at pH 6.8 as the medium and a temperature of 37±0.5℃. Six lozenges were placed into the six tubes of the disintegration apparatus basket, the instrument was started, and the time from the start to the complete disintegration of the tablets (without solid particles remaining) was recorded. The average time for the six tablets was taken (unit: s).

[0059] 5. Taste rating Sensory evaluation method was used: 50 volunteers (aged 20-50, half male and half female, no oral diseases) held the lozenge in their mouths for 30 seconds and then scored it according to the scoring criteria (1 point: extremely bitter, with obvious foreign body sensation; 2 points: somewhat bitter, with foreign body sensation; 3 points: slightly bitter, with weak foreign body sensation; 4 points: slightly sweet, with no foreign body sensation; 5 points: refreshingly sweet, with a cooling sensation, with no foreign body sensation). The average score of the 50 volunteers was taken.

[0060] 6. Sleep improvement rate measurement Referring to the spontaneous activity experiment in mice in "Pharmacological Experimental Methodology": 130 ICR mice (weighing 20-22g, half male and half female, SPF grade) were randomly divided into 13 groups (n=10 per group). The blank group was administered 0.5% sodium carboxymethyl cellulose solution by gavage, while the drug-treated group was administered 200mg / kg of lozenge suspension (the lozenges were ground into powder and prepared with 0.5% sodium carboxymethyl cellulose solution). 30 minutes after gavage, the mice were placed in a spontaneous activity box, and the number of spontaneous activities within 10 minutes was recorded. Sleep improvement rate (%) = (number of spontaneous activities in the blank group - number of spontaneous activities in the drug-treated group) / number of spontaneous activities in the blank group × 100%.

[0061] 7. Accelerated stability test According to the guidelines for drug stability testing in Chapter 9001 of the General Section of Part IV of the Chinese Pharmacopoeia 2020: the tablets were sealed in aluminum-plastic blister packs and placed in a constant temperature and humidity chamber at 40±2℃ and 75±5% relative humidity; samples were taken at the initial time and at 6 months to measure the polysaccharide content; the accelerated stability retention rate (%) = (polysaccharide content after 6 months / initial polysaccharide content) × 100%.

[0062] The results are shown in Table 1.

[0063] Table 1 Performance parameters of the lozenges obtained in Examples 1-3 and Comparative Examples 1-9 Group Polysaccharide retention rate (%) Dissolution rate (%) at 15 min Tablet hardness (N) Disintegration time (s) Taste rating (points) Sleep improvement rate (%) Accelerated stability retention rate (%) Example 1 90 83 42.1 52 4.2 40 86 Example 2 93 86 45.1 48 4.5 43 89 Example 3 96 89 48.0 44 4.8 46 92 Comparative Example 1 78 72 46.1 46 4.7 32 75 Comparative Example 2 95 88 47.0 45 4.6 28 91 Comparative Example 3 83 76 44.1 48 4.5 34 80 Comparative Example 4 73 67 42.1 52 4.2 28 69 Comparative Example 5 94 85 47.0 47 3.6 44 90 Comparative Example 6 95 87 31.4 35 4.7 45 91 Comparative Example 7 94 88 27.4 38 4.6 44 90 Comparative Example 8 89 79 47.0 55 3.8 43 91 Comparative Example 9 96 89 47.0 45 4.7 35 92 Using Example 3 as the control group, the performance differences and causes of Comparative Examples 1-9 are analyzed as follows: Comparative Example 1 (where Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres were replaced with microcrystalline cellulose), the polysaccharide retention rate decreased from 96% to 78% (a decrease of 18.8%), the 15-minute dissolution rate decreased from 89% to 72% (a decrease of 19.1%), the sleep improvement rate decreased from 46% to 32% (a decrease of 30.4%), and the accelerated stability retention rate decreased from 92% to 75% (a decrease of 18.5%). Analysis of the causes: The absence of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres caused the dual polysaccharides to lose their nanoscale physical encapsulation protection. During preparation and storage, they are easily oxidized and degraded by contact with oxygen, resulting in a significant decrease in stability. Simultaneously, without the slow intestinal release effect of the composite nanospheres, the polysaccharides cannot maintain their efficacy after rapid dissolution in vivo, and bioavailability is reduced due to the loss of encapsulation protection, ultimately leading to a significant decline in multiple performance indicators.

[0064] Comparative Example 2 (where the fructooligosaccharide-γ-aminobutyric acid graft was replaced with γ-aminobutyric acid), the sleep improvement rate decreased from 46% to 28% (a decrease of 39.1%). The reason for this is that the absence of the fructooligosaccharide-γ-aminobutyric acid graft exposes γ-aminobutyric acid directly to the acidic environment of the stomach. This acidity leads to a degradation rate of over 50% of γ-aminobutyric acid, preventing it from effectively reaching the central nervous system to exert its sedative effect. Furthermore, the loss of fructooligosaccharide's regulatory function on the gut microbiota disrupts the gut-central nervous system synergistic regulatory pathway. Therefore, relying solely on the single action of γ-aminobutyric acid and Ganoderma lucidum polysaccharides significantly weakens the sleep-aiding effect.

[0065] Comparative Example 3 (Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres were prepared without ultrasonic treatment), the polysaccharide retention rate decreased from 96% to 83% (a decrease of 13.5%), the 15-minute dissolution rate decreased from 89% to 76% (a decrease of 14.6%), and the sleep improvement rate decreased from 46% to 34% (a decrease of 26.1%). Analysis of the reasons: The lack of ultrasonic treatment led to an increase in microsphere particle size and a significant decrease in encapsulation efficiency—the smaller specific surface area of ​​the larger microspheres prevents sufficient oxygen isolation, increasing the oxidative degradation of the polysaccharides and thus reducing the polysaccharide retention rate; simultaneously, the larger microspheres dissolve faster in the intestine, failing to achieve "continuous release," resulting in reduced bioavailability and a weakened sleep improvement rate. This indicates that ultrasonic treatment is a necessary step to control microsphere particle size and ensure effective encapsulation.

[0066] Comparative Example 4 (the drying method of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres was changed to spray drying), the polysaccharide retention rate decreased from 96% to 73% (a decrease of 23.9%), the 15-minute dissolution rate decreased from 89% to 67% (a decrease of 24.7%), and the accelerated stability retention rate decreased from 92% to 69% (a decrease of 25.0%). Analysis of the reasons: The inlet temperature of spray drying is much higher than the tolerance temperature of polysaccharides, leading to the breakage of glycosidic bonds in the disaccharides and the destruction of the active structure, thus significantly reducing the polysaccharide retention rate. Simultaneously, the high temperature causes the surface of the microspheres to melt and clump, forming a dense layer, making it difficult for the polysaccharides to be released during subsequent dissolution, significantly reducing the 15-minute dissolution rate. The clumped microspheres are more prone to moisture absorption in the accelerated test, further aggravating polysaccharide degradation and accelerating the decrease in stability retention rate. This indicates that vacuum freeze drying is a key process for protecting polysaccharide activity and preventing microsphere clumping.

[0067] Comparative Example 5 (xylitol replaced with erythritol), the taste score dropped from 4.8 to 3.6. The reason is that the synergistic effect of xylitol and erythritol was lost. The cooling sensation was too strong after doubling the amount of erythritol, and the ability to mask the slightly bitter taste of polysaccharides was reduced, resulting in an uncoordinated taste of "too cooling and slightly bitter" in the lozenge, which led to a significant drop in the score.

[0068] Comparative Example 6 (microcrystalline cellulose was replaced with hydroxypropyl methylcellulose), the tablet hardness decreased from 48.0 N to 31.4 N (a decrease of 34.6%), and the disintegration time decreased from 44 s to 35 s (a decrease of 20.5%). Analysis of the reasons: Microcrystalline cellulose has a dual function of filling and disintegration regulation; its absence causes the tablet to lose this "filling-disintegration balance." Hydroxypropyl methylcellulose can only provide adhesion and cannot form a tight particle-bound structure, resulting in reduced tablet hardness and increased brittleness during transportation. Simultaneously, the porous structure without microcrystalline cellulose absorbs moisture, leading to excessively rapid disintegration, which does not meet the requirement of "slow dissolution upon ingestion" for lozenges.

[0069] Comparative Example 7 (compression pressure of 4 MPa) showed that the tablet hardness decreased from 48.0 N to 27.4 N (a decrease of 42.9%). The reason for this was that the compression pressure was below the suitable range of 6-10 MPa, resulting in insufficient van der Waals forces and mechanical bonding between the material particles, leading to a loose tablet structure that could not meet the storage and transportation requirements after industrial production.

[0070] Comparative Example 8 (without added citric acid): the dissolution rate at 15 minutes decreased from 89% to 79% (a decrease of 11.2%), the disintegration time increased from 44 seconds to 55 seconds (an increase of 25.0%), and the taste score decreased from 4.8 to 3.8. Analysis: The absence of citric acid resulted in an unfavorable oral pH for polysaccharide dissolution, leading to the formation of polysaccharide aggregates and significantly reduced solubility, resulting in slower dissolution and prolonged disintegration time. Simultaneously, the lack of citric acid to neutralize the cloying sweetness of xylitol and erythritol resulted in an overly sweet taste, leading to a lower score.

[0071] Comparative Example 9 (without added fructooligosaccharides), the sleep improvement rate decreased from 46% to 35% (a decrease of 23.9%). The reason for this is that the lack of fructooligosaccharides weakens the regulatory effect of gut microbiota. The limited fructooligosaccharide content in the fructooligosaccharide-γ-aminobutyric acid (GABA) grafted compound prevents sufficient proliferation of beneficial gut bacteria (such as Bifidobacteria), leading to a reduction in short-chain fatty acids (SCFAs) produced by these probiotics. SCFAs can enhance the sedative effect of GABA through the blood-brain barrier, and their reduction weakens the sleep improvement effect. This indicates that fructooligosaccharides are a necessary excipient for "gut-central nervous system synergistic regulation."

[0072] In summary, the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres reduce the oxidative inactivation of the two polysaccharides through nanoscale encapsulation, prolonging the in vivo action time and improving bioavailability. The fructooligosaccharide-γ-aminobutyric acid (GABA) grafted compound protects GABA from gastric acid degradation through chemical grafting and synergistically regulates intestinal flora to enhance sleep-aiding effects. The combination of microcrystalline cellulose and hydroxypropyl methylcellulose balances tablet hardness and disintegration, ensuring physical stability. Xylitol and erythritol synergistically optimize the taste, while citric acid improves polysaccharide solubility and flavor through pH adjustment. Through multiple effects of structural protection, synergistic efficacy, and physicochemical regulation, the components achieve a comprehensive improvement in the lozenge's performance, including "high stability, high absorption, and good taste," meeting the requirements for the industrial production and application of pharmaceutical lozenges.

[0073] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide, characterized in that, By weight, its constituent raw materials include: 15-25 parts of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres, 4-9 parts of fructooligosaccharide-γ-aminobutyric acid graft, 10-16 parts of xylitol, 10-16 parts of erythritol, 5-10 parts of microcrystalline cellulose, 2-4 parts of hydroxypropyl methylcellulose, 1-3 parts of γ-aminobutyric acid, 0.3-0.6 parts of magnesium stearate, and 0.2-0.5 parts of citric acid.

2. The lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide according to claim 1, characterized in that, By weight, the raw materials of the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres include: 20-30 parts of broken Ganoderma lucidum spore powder, 20-30 parts of Dendrobium officinale ultrafine powder, 3.2-7.2 parts of sodium alginate, 0.4-1.2 parts of chitosan, and 2-4.8 parts of calcium chloride.

3. The lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide according to claim 2, characterized in that, The preparation method of Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres includes the following steps: 1) Weigh out the broken-cell wall Ganoderma lucidum spore powder and place it in a constant temperature and humidity chamber at 35-40℃ and 70%-80% humidity for 12-24 hours to activate it; weigh out the Dendrobium officinale ultrafine powder and place it in a forced-air drying oven at 75-85℃ for 8-12 hours to dry it. 2) Take the activated and broken-cell wall Ganoderma lucidum spore powder, add 12-18 times the weight of the broken-cell wall Ganoderma lucidum spore powder in purified water, and then transfer it to a high-speed shearing machine. Extract for 8-12 minutes at a shearing speed of 10000-14000 r / min and a water bath temperature of 90-100℃. Filter the extract through a 0.20-0.22μm filter membrane to obtain Ganoderma lucidum spore powder polysaccharide extract. Take the dried Dendrobium officinale ultrafine powder and repeat the above extraction steps to obtain Dendrobium officinale polysaccharide extract. 3) After mixing the Ganoderma lucidum spore powder polysaccharide extract and the Dendrobium officinale polysaccharide extract evenly, add sodium alginate and chitosan, transfer to an ultrasonic reactor, stir at 350-450 r / min for 25-35 min, and then sonicate for 8-12 min at a frequency of 35-45 kHz and a power of 200-300 W to obtain a nano-mixture. 4) Weigh calcium chloride, add 20-30 times the mass of purified water to prepare a calcium chloride solution, and place it in a constant temperature reaction tank at 32-38℃; 5) Pass the nano-mixture through a microfluidic chip with a diameter of 45-50 μm and drop it into a calcium chloride solution at a flow rate of 2-4 mL / h. Solidify at a constant temperature for 20-30 min to obtain white suspended Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres. Then wash the composite nanospheres with purified water 3-4 times, and centrifuge at 3000-4000 r / min for 5-8 min after each wash. Place the purified composite nanospheres in a vacuum freeze dryer and pre-freeze at -45℃ to -35℃ for 1.5-2.5 h. Freeze-dry at a sublimation temperature of 30-40℃ and a vacuum degree of 1-10 Pa for 12-16 h. Pulverize and pass through a 100-120 mesh sieve to obtain the final product.

4. The lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide according to claim 3, characterized in that, In step 2), the polysaccharide content of the Ganoderma lucidum spore powder polysaccharide extract is 18%-22%, and the polysaccharide content of the Dendrobium officinale polysaccharide extract is 15%-18%.

5. The lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide according to claim 3, characterized in that, In step 5), the constant temperature curing temperature is 32-38℃.

6. The lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide according to claim 2, characterized in that, The raw materials for the fructooligosaccharide-γ-aminobutyric acid graft by weight are: 28-32 parts fructooligosaccharide, 9-11 parts γ-aminobutyric acid, 0.04-0.14 parts citric acid, and appropriate amounts of purified water and anhydrous ethanol.

7. The lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide according to claim 6, characterized in that, The degree of polymerization of fructooligosaccharides is 3-5; the mass ratio of purified water to the total mass of fructooligosaccharides and γ-aminobutyric acid is 1.2-1.5:1, and the volume ratio of anhydrous ethanol to purified water is 2.5-3.5:

1.

8. The lozenge containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide according to claim 7, characterized in that, The preparation method of fructooligosaccharide-γ-aminobutyric acid grafts includes the following steps: a. Take the oligofructose and dry it in a vacuum drying oven at 60-70℃ for 2-3 hours; take the γ-aminobutyric acid and dry it in a vacuum drying oven at 60-70℃ for 1-2 hours. b. Add the dried fructooligosaccharides and γ-aminobutyric acid to a stainless steel reactor, then add purified water and stir at 200-300 r / min until completely dissolved. Add citric acid, then purge the air in the reactor with nitrogen at a flow rate of 100-200 mL / min. Repeat this process 3 times, then raise the temperature to 65-75℃ and react at a constant temperature for 2.5-4 h. c. After the reaction is complete, cool to 20-25℃, add anhydrous ethanol, stir well, and let stand for 1.5-2.5h. Then centrifuge at 3000-4000r / min for 8-12min to collect the precipitate of fructooligosaccharide-γ-aminobutyric acid graft. Wash the precipitate with anhydrous ethanol 2-3 times, centrifuging for 5-8min after each wash. Finally, place the precipitate in a vacuum drying oven at 55-65℃ and 1-10Pa vacuum degree to dry for 8-10h, pulverize and pass through a 100-120 mesh sieve to obtain the fructooligosaccharide-γ-aminobutyric acid graft.

9. A method for preparing lozenges containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide according to any one of claims 1-8, characterized in that, Includes the following steps: S1. Place the Ganoderma lucidum spore powder polysaccharide-Dendrobium officinale polysaccharide composite nanospheres and fructooligosaccharide-γ-aminobutyric acid graft material in a three-dimensional mixer and mix at 15-25 r / min for 15-25 min. Then add xylitol, erythritol, microcrystalline cellulose, hydroxypropyl methylcellulose, γ-aminobutyric acid, and citric acid, and continue mixing for 10-15 min. Finally, add magnesium stearate and mix at 50-100 r / min for 5-8 min. S2. The mixture obtained in S1 is processed using a rotary tablet press. The tablets are compressed under a compression pressure of 6-10 MPa and a compression speed of 40-60 tablets / min to obtain tablets containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide.

10. The method for preparing lozenges containing Ganoderma lucidum spore powder polysaccharide and Dendrobium officinale polysaccharide according to claim 9, characterized in that, The tablets weigh 0.5-0.8g and are 2.5-4.5mm thick.