Taste masking treatment method of panax notoginseng saponins

Abstract

The invention discloses a taste masking treatment method of panax notoginseng saponins, which comprises the following specific steps: step 1, putting panax notoginseng saponins particles and an inclusion material into a hot-melt spray granulation fluidized bed to prepare hot-melt particles; wherein the hot melting temperature is 65-120 DEG C, the atomization pressure is 0.3-0.5 MPa, and the mass ratio of the panax notoginseng total saponin particles to the inclusion material is 1: (0.5-3); step 2, respectively sieving the hot melt particles prepared in the step 1 through a 50-mesh sieve and a 65-mesh sieve, and collecting 50-65-mesh intermediate particles;

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine pharmaceutical technology, specifically to a method for masking the taste of total saponins from Panax notoginseng. Background Technology

[0002] Cardiovascular and cerebrovascular diseases such as coronary heart disease, cerebral thrombosis, hypertension, and cerebral infarction are among the most common and harmful diseases in the world today, seriously threatening human health and life. In current medicine, oral tablet versions of Panax notoginseng are mainly available as Xuesaitong tablets, Xueshuantong tablets, and Sanqi Shangyao tablets. Because these dosage forms are exposed, the drugs inevitably come into direct contact with the taste buds in the mouth during ingestion, often resulting in a distinctive taste or bitterness. Therefore, these drugs often suffer from bitterness, difficulty in swallowing, and poor patient compliance.

[0003] Currently, the main methods for masking the taste of Panax notoginseng total saponins are: (1) Add flavoring agent The method of directly adding flavoring agents to alter the unpleasant taste of drugs relies on the principle of modulating the drug's stimulating effect on taste buds through other taste components, thereby masking the drug's unpleasant taste. Flavoring agents are categorized as sweeteners, taste bud modifiers, numbing agents, gelling agents, and flavoring agents. While adding sucralose (600 times sweeter than sucrose) or neotame (7000 times sweeter than sucrose) solves some taste problems, for highly water-soluble Panax notoginseng saponins, a sweet-then-bitter aftertaste may occur. Furthermore, the aftertaste of drugs treated with flavoring agents lingers for a relatively long time, ultimately failing to effectively change the overall taste.

[0004] (2) Inclusion and powder coating The principle behind flavor masking using cyclodextrin inclusion complexes is that the inclusion process between the host and guest molecules is a physical process. The formation conditions of these complexes are related to various factors such as molecular polarity and hydrogen bonding. Panax notoginseng total saponins contain multiple components and are highly hydrophilic. Using grinding or saturated solution methods results in low binding between the drug molecules and cyclodextrin, leading to poor inclusion effects and a persistent bitter taste, failing to effectively change the unpleasant bitterness of the drug. While ordinary powder coating can mask some bitterness, its effectiveness is limited when used in chewable tablets because chewing disrupts the coating layer, releasing unpleasant-tasting substances. Summary of the Invention

[0005] In view of the above-mentioned shortcomings of the existing technology, the purpose of the present invention is to provide a method for masking the bitterness of Panax notoginseng total saponins, so as to solve the problem that the existing technology has a poor effect on removing the bitterness of Panax notoginseng total saponins and still has a strong bitterness when taken.

[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: A method for masking the taste of total saponins from Panax notoginseng, the specific steps of which are as follows: Step 1: Add the total saponins of Panax notoginseng granules and the inclusion material into a hot melt spray granulation fluidized bed to prepare hot melt microparticles; wherein, the hot melt temperature is 65℃-120℃, the atomization pressure is 0.3MPa-0.5MPa, and the mass ratio of total saponins of Panax notoginseng granules to inclusion material is 1:(0.5-3). Step 2: Pass the hot-melt microparticles prepared in Step 1 through a 50-mesh sieve and a 65-mesh sieve respectively, and collect the intermediate particles of 50-65 mesh.

[0007] Preferably, in step 1, the inclusion material is composed of stearic acid and glyceryl monostearate, and the mass ratio of stearic acid to glyceryl monostearate is (5-7):(3-5).

[0008] Preferably, in step 1, the fan frequency is 35Hz-40Hz.

[0009] Preferably, in step 1, the temperature during granulation is maintained at 65°C-75°C.

[0010] Preferably, in step 1, the total saponins of Panax notoginseng granules are obtained through the following steps: S1: Mix total saponins of Panax notoginseng, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and lactose; wherein the mass ratio of total saponins of Panax notoginseng, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and lactose is 63:50:50:153. S2: Add the mixed material from S1 into a spray granulator. Spray granulation is performed using a peristaltic pump with a povidone K30 aqueous solution. Spray granulation is carried out under the conditions of atomization pressure of 0.45~0.62 bar, inlet air temperature of 44~50℃, and peristaltic pump speed of 35~85 rpm to prepare Panax notoginseng total saponin granules. The concentration of povidone K30 in the povidone K30 aqueous solution is 8 wt%, and the mass ratio of Panax notoginseng total saponins to povidone K30 aqueous solution is 52:50.

[0011] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention fundamentally solves the technical pain points of traditional direct hot-melt granulation of Panax notoginseng total saponin powder by first fluidizing granulation to form rounded particles and then hot-melt coating to form a functional shell. In the initial fluidized bed granulation stage, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and lactose were used as excipients. Combined with precisely controlled spray granulation parameters, pre-granules with uniform particle size, suitable mechanical strength, and optimized specific surface area were formed. These pre-granules not only have good flowability and can form a stable and uniform fluidized state in the subsequent hot-melt fluidized bed, avoiding the problems of local agglomeration, dead bed, or fine powder escape that are prone to occur when powder is directly hot-melted, but also provide a stable carrier skeleton for hot-melt coating. This allows the molten coating material (a mixture of stearic acid and glyceryl monostearate) to spread evenly on the surface of the pre-granules and cool and solidify, ultimately forming regular spherical core-shell structured particles. This completely solves the defects of uncontrolled particle shape and wide particle size distribution caused by direct hot melting. At the same time, the dense shell can completely encapsulate the total saponins of Panax notoginseng, greatly improving the taste masking effect, significantly increasing the bitterness threshold, and significantly improving patient medication compliance.

[0012] 2. The method described in this invention synergistically improves drug release characteristics, production efficiency, and product stability. Regarding release regulation, the optimized mass ratio of stearic acid to glyceryl monostearate leverages the hydrophobicity of stearic acid for long-lasting sustained release while the hydrophilicity of glyceryl monostearate promotes effective initial release. Combined with particle screening, this achieves a biphasic release characteristic with a release rate exceeding 60% at 30 minutes and nearly 90% at 90 minutes, fully meeting the requirements for oral sustained-release formulations and exhibiting a more reasonable release curve compared to traditional direct coating processes. In terms of production efficiency, the coordinated use of fan frequency, hot-melt temperature, and atomization pressure not only controls the moisture content of the hot-melt microparticles to below 3%, but also saves 20% energy and shortens the granulation cycle compared to conventional processes, increasing the overall yield to over 90%, making it more suitable for industrial mass production. Regarding stability, the core-shell structure of the particles results in high mechanical strength, and the shell effectively isolates external moisture and oxygen, far superior to products prepared by traditional processes, providing strong assurance for the quality control and clinical reliability of Panax notoginseng total saponins oral solid dosage forms. Attached Figure Description

[0013] Figure 1 The bitterness response signal curve of Panax notoginseng total saponins raw material.

[0014] Figure 2 PCA dimensionality reduction results for Panax notoginseng total saponins raw material, purified water, 25% coated Panax notoginseng total saponins hot-melt microparticles, 50% coated Panax notoginseng total saponins hot-melt microparticles, and 75% coated Panax notoginseng total saponins hot-melt microparticles.

[0015] Figure 3The regression line plot of the MVR model training was constructed based on the electronic tongue test signal diagrams of Panax notoginseng total saponins raw materials, purified water, and Panax notoginseng total saponins hot-melted microparticles.

[0016] Figure 4 An SVM model for predicting bitterness was constructed using electronic tongue test signals of Panax notoginseng total saponins raw materials, purified water, and Panax notoginseng total saponins hot-melted microparticles.

[0017] Figure 5 a is an electron microscope image of the total saponins of Panax notoginseng; Figure 5 b is an electron microscope image of the hot-melted microparticles of total saponins from Panax notoginseng.

[0018] Figure 6 This is a graph showing the bitterness response signal of pure water.

[0019] Figure 7 The image shows the bitterness response signal curve of the hot-melted microparticles of total saponins from Panax notoginseng prepared in Example 5.

[0020] Figure 8 The image shows the bitterness response signal curve of the hot-melted microparticles of total saponins from Panax notoginseng prepared in Example 6.

[0021] Figure 9 The image shows the bitterness response signal curve of the hot-melted microparticles of total saponins of Panax notoginseng prepared in Example 7. Detailed Implementation

[0022] This invention will describe the technical solutions of the embodiments of the invention clearly and completely. Obviously, the described embodiments are only some embodiments of the invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on this invention are within the scope of protection of this invention.

[0023] Unless otherwise specified in the specific circumstances, the numerical ranges listed herein include upper and lower limits, as well as all integers and fractions within that range, but are not limited to the specific values ​​listed when the range is defined.

[0024] I. A method for masking the taste of total saponins from Panax notoginseng Step 1: Add the total saponins of Panax notoginseng granules and the inclusion material into a hot melt spray granulation fluidized bed to prepare hot melt microparticles; wherein, the hot melt temperature is 65℃-120℃, the atomization pressure is 0.3MPa-0.5MPa, and the mass ratio of total saponins of Panax notoginseng granules to inclusion material is 1:(0.5-3). Step 2: Pass the hot-melt microparticles prepared in Step 1 through a 50-mesh sieve and a 65-mesh sieve respectively, and collect the intermediate particles of 50-65 mesh.

[0025] In researching existing technologies, this invention discovered numerous problems with traditional Panax notoginseng total saponin masking and granulation processes. For example, existing technologies typically involve directly mixing Panax notoginseng total saponin powder with hot-melt materials for granulation. However, the average particle size of the raw material Panax notoginseng total saponin powder is extremely small, resulting in a large specific surface area and high surface energy, making it prone to agglomeration. This makes it difficult for the hot-melt material to uniformly coat the powder, leading to a large number of clumps and free hot-melt material, thus hindering successful granulation. Furthermore, this invention also found that the existing technology is not ideal for masking the taste of Panax notoginseng total saponins. When a single hot-melt material is used, either the high melting point or insufficient fluidity results in poor coating and poor masking effect, with most subjects reporting a strong bitter taste, or the material has a single property, making it difficult to simultaneously achieve both masking effect and drug dissolution performance. Traditional masking processes rely on flavoring agents such as fragrances and sucrose, but such treatment cannot completely mask the extreme bitterness of Panax notoginseng total saponins. Subjects participating in the experiment all reported an extremely strong bitter taste that even caused vomiting. Moreover, adding a large amount of sweetener does not conform to the development trend of low sugar and simplified excipients in pharmaceuticals.

[0026] To address these issues, this invention relies on a suitable hot-melt spray granulation fluidized bed equipment (for which a separate patent application has been filed) and focuses on systematic improvements in both process and auxiliary materials. First, this invention optimizes the hot-melt material formulation by using a specific mass ratio of stearic acid and glyceryl monostearate. This compound system achieves a lower melting point, improves fluidity after melting, and avoids problems such as insufficient melting of a single material leading to coating gaps or excessive coating affecting dissolution. Further research revealed that, through the fibrous support structure of microcrystalline cellulose and the crystalline structure of lactose, the pre-granules form stable "rounded particles." This structure ensures that the subsequently melted compound hot-melt material can only spread uniformly on the surface of the pre-granules and solidify upon cooling, rather than being agglomerated into irregular clumps as in direct hot-melt powder. This completely solves the problem of uneven coating, which is the core breakthrough in overcoming the defects of traditional powder hot-melt processes. The compound hot-melt material achieves a dual effect through synergistic composition. The hydrophobicity of stearic acid can effectively isolate the total saponins of Panax notoginseng from direct contact with the taste buds, reducing the perception of bitterness from the source. The hydrophilicity of glyceryl monostearate can improve the fluidity of the material after melting, ensuring that the coating layer is uniform and dense. The combination of the two not only enhances the masking effect, but also does not hinder the normal dissolution of the drug in the body.

[0027] Ultimately, the Panax notoginseng total saponins hot-melt particles prepared by this invention are all regular spherical in shape, with particle size and range fully meeting the requirements for subsequent processing. Furthermore, the bitterness level of the hot-melt particles is significantly reduced; only some subjects reported a significant bitterness, while most subjects only experienced a slight bitterness. No subjects reported an extremely strong bitterness requiring immediate spitting or causing vomiting. This represents a qualitative improvement over traditional single-material or flavor masking methods. The process stability is significantly enhanced, with no instances of spray gun clogging, material collapse, or wall adhesion throughout the process, demonstrating excellent prospects for industrial application. The drug dissolution performance fully meets the dissolution time requirements stipulated in the pharmacopoeia, ensuring normal efficacy. Simultaneously, a highly fitted linear model is constructed using electronic tongue technology. Combined with principal component analysis, model construction, and bitterness value prediction analysis, the reliability and repeatability of the masking effect are objectively verified. The reliable model from existing technologies proves that the method described in this invention completely solves the triple problems of traditional processes: "difficulty in applying heat-sensitive drugs, granulation of easily oxidized drugs, and poor masking effect for bitter drugs," achieving a dual improvement in patient compliance and clinical efficacy stability.

[0028] In some embodiments of the present invention, in step 1, the encapsulating material is composed of stearic acid and glyceryl monostearate, with a mass ratio of stearic acid to glyceryl monostearate of (5-7):(3-5). The present invention optimizes the ratio of stearic acid to glyceryl monostearate. Although these two materials are common encapsulating materials, in practical use, the present invention has found that, when stearic acid is used alone, its main problem lies in the contradiction between the encapsulation effect and the flowability of the particles. Stearic acid itself has a relatively high melting point and poor flowability after melting. During the hot-melt encapsulation process, it is difficult to form a uniform and dense encapsulation layer on the surface of the Panax notoginseng total saponins pre-particles. Insufficient melting leads to gaps in the encapsulation layer, directly exposing the internal Panax notoginseng total saponins, which then cause a strong bitter taste upon contact with the taste buds. Furthermore, even if encapsulation is achieved, insufficient flowability results in localized excessive thickness or accumulation of the encapsulation layer, forming an irregular encapsulation morphology. In practical terms, when stearic acid was used alone, most subjects reported a significant bitter taste, with some even spitting it out immediately due to the intense bitterness, indicating that the masking effect fell far short of expectations. Furthermore, stearic acid's strong hydrophobicity meant that even if a complete coating layer was formed, its excessive hydrophobicity hindered drug dissolution in vivo, resulting in a slower dissolution rate. This failed to meet the pharmacopoeia's requirements for the dissolution time of total saponins from Panax notoginseng, leading to the dual problem of insufficient masking while potentially affecting efficacy. When glyceryl monostearate was used alone, the core drawback lay in the insufficient density and stability of the coating layer. Although glyceryl monostearate had a relatively low melting point and good fluidity after melting, allowing for rapid spreading on the surface of pre-particles, its relatively strong hydrophilicity resulted in a loose coating structure that could not effectively isolate total saponins from the external environment. On the one hand, a loose coating layer is insufficient to prevent the drug from contacting the taste buds, resulting in poor taste masking. Subjects can still clearly perceive a strong bitter taste, similar to the shortcomings of traditional single-material taste masking. On the other hand, a loose coating layer is prone to damage and detachment during subsequent processing or storage, which not only further weakens the taste masking effect but also leads to unstable drug dissolution behavior. This results in some granules dissolving rapidly and prematurely due to coating layer damage, while others suffer from uneven dissolution due to residual coating material, ultimately failing to achieve the core objective of "effective taste masking and controllable dissolution." To address this, the present invention optimizes the use of stearic acid and glyceryl monostearate. First, by combining them in a specific mass ratio, the characteristics of both are balanced, avoiding the extreme defects of single materials.This invention explicitly employs a mass ratio of stearic acid to glyceryl monostearate (5-7):(3-5) for compounding. The hydrophobicity of stearic acid compensates for the loose coating layer and ineffective bitterness isolation when glyceryl monostearate is used alone. Conversely, the hydrophilicity and good flowability of glyceryl monostearate improve the defects of stearic acid when used alone, such as high melting point, poor flowability after melting, and the tendency to form uneven coating layers. After compounding, stearic acid retains its ability to build a dense coating shell, while glyceryl monostearate enhances the spreadability of the molten material, ensuring that the coating layer uniformly covers the surface of the Panax notoginseng total saponins preparticles, avoiding the problems of "coating gaps" or "local accumulation" that occur with single materials. Secondly, this invention discovers that by controlling the melting temperature after compounding to optimize the melting state of the material, process defects can be further avoided. After compounding stearic acid and glyceryl monostearate, the melting temperature can be reduced to 65-75℃, lower than the melting point of stearic acid alone. This temperature optimization solves the problems of insufficient melting and easy clogging of the spray gun caused by the high melting point of stearic acid alone, while avoiding the thermal degradation of Panax notoginseng saponins due to excessive temperature. Simultaneously, it ensures that the compound material maintains suitable melt flowability, allowing it to spread quickly and evenly on the surface of the pre-particles, forming a structurally stable coating layer. This series of adjustments synergistically improves the coating layer performance, achieving both taste masking and controllable dissolution. Practical application shows that using this compounding scheme significantly reduces the bitterness reported by subjects, far superior to using stearic acid or glyceryl monostearate alone, proving that the compound coating layer designed in this invention effectively isolates Panax notoginseng saponins from the taste buds. Furthermore, dissolution tests show that the hot-melt microparticles prepared by the compounding scheme designed in this invention all meet the United States Pharmacopeia requirement of "dissolution rate of not less than 60% within 30 minutes," avoiding the slow dissolution caused by the excessive hydrophobicity of stearic acid alone and solving the dissolution instability caused by the loose coating layer of glyceryl monostearate alone, achieving the dual goals of effective taste masking and controllable dissolution.

[0029] In some embodiments of the present invention, in step 1, the fan frequency is 35Hz-40Hz. The present invention controls the fan frequency within a suitable range to ensure that the pre-particles maintain a uniform fluidization state during the hot-melting process, avoiding bed collapse and adhesion to the wall due to poor fluidization.

[0030] In some embodiments of the present invention, the granulation temperature is maintained at 65°C-75°C in step 1. The present invention controls the granulation temperature within a suitable range, ensuring that the hot-melt material is fully melted to form a dense coating layer, while avoiding excessive temperature causing thermal degradation of Panax notoginseng saponins, and simultaneously solving the problem of spray gun clogging caused by improper temperature.

[0031] In some embodiments of the present invention, in step 1, considering the problem of directly using Panax notoginseng total saponin powder, the present invention designs a two-step process: first, fluidized bed granulation to construct spherical particles, and then hot-melt coating. First, Panax notoginseng total saponins, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and lactose are mixed in a specific ratio. Pre-particles are prepared by combining appropriate atomization pressure and inlet air temperature. The average particle size of the pre-particles is significantly larger than that of the raw material powder, and the bulk density is also significantly improved. By constructing a stable carrier structure through pre-particles, the agglomeration tendency of the raw material powder is fundamentally reduced, providing a uniform and stable particle substrate for subsequent hot-melt coating. The Panax notoginseng total saponin particles described in the present invention are obtained through the following steps: S1: Mix total saponins of Panax notoginseng, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and lactose; wherein the mass ratio of total saponins of Panax notoginseng, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and lactose is 63:50:50:153; S2: Add the mixed material from S1 into a spray granulator. Spray granulation is performed using a peristaltic pump with a povidone K30 aqueous solution. Spray granulation is carried out under the conditions of atomization pressure of 0.45~0.62 bar, inlet air temperature of 44~50℃, and peristaltic pump speed of 35~85 rpm to prepare Panax notoginseng total saponin granules. The concentration of povidone K30 in the povidone K30 aqueous solution is 8 wt%, and the mass ratio of Panax notoginseng total saponins to povidone K30 aqueous solution is 52:50.

[0032] II. Examples and Comparative Examples Example

[0033] Step 1: Use 0.24 kg of total saponins of Panax notoginseng powder, 0.24 kg of microcrystalline cellulose, 0.19 kg of low-substituted hydroxypropyl cellulose, and 0.58 kg of lactose. Prepare an aqueous solution with povidone K30 to obtain an aqueous solution with a povidone K30 content of 8 wt%.

[0034] Step 2: Mix total saponins of Panax notoginseng, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and lactose, and spray an 8% povidone K30 aqueous solution using a peristaltic pump. The atomization pressure is 0.45~0.62 bar, the inlet air temperature is 44~50℃, and the peristaltic pump speed is 35~85 rpm to obtain total saponins of Panax notoginseng granules.

[0035] Electron microscopy was performed on the raw material, total saponins of Panax notoginseng powder, and the total saponins of Panax notoginseng particles prepared in Example 1, and their bulk density was determined. Figure 5 a and Figure 5 As shown in b. Regarding particle size, Figure 5 As can be clearly seen in a, the total saponins of Panax notoginseng powder used as raw material has a very small particle size, with an average particle size of only 166μm. Figure 5The particle size of the total saponins from Panax notoginseng in sample b was significantly increased, with an average particle size of 288 μm. In terms of bulk density, the total saponins from Panax notoginseng particles prepared in Example 1 showed a significant increase. This indicates that the total saponins from Panax notoginseng powder has completed its initial encapsulation. By constructing a stable carrier structure through pre-particles, the tendency of the raw material powder to agglomerate is fundamentally reduced, providing a uniform and stable particle substrate for subsequent hot-melt coating. Example

[0036] The total saponins of Panax notoginseng prepared in Example 1 were used as raw materials.

[0037] Step 1: The dosage of Panax notoginseng total saponins granules is 0.1 kg, the dosage of stearic acid is 0.025 kg, and the dosage of glyceryl monostearate is 0.025 kg.

[0038] Step 2: Heat and melt the stearic acid and glyceryl monostearate from Step 1, with the melting temperature of the materials being 75℃. Then add the total saponins of Panax notoginseng and perform hot melt spray granulation with an atomization pressure of 0.2~0.4Mpa, an inlet air temperature of 18~25℃, a heater temperature of 110℃, a fan frequency of 35~40HZ, and a peristaltic pump speed of 10~12rpm to obtain hot melt granules of total saponins of Panax notoginseng. Example

[0039] The method is an adjustment based on Example 2, except that the amount of stearic acid is 0.03 kg and the amount of glyceryl monostearate is 0.02 kg. The hot melt temperature is 70°C. All other steps are exactly the same as in Example 2. Example

[0040] The method is an adjustment based on Example 2, except that the amount of stearic acid is 0.035 kg and the amount of glyceryl monostearate is 0.015 kg. The hot melt temperature is 65°C. All other steps are exactly the same as in Example 2. Example

[0041] The method is an adjustment based on Example 2, except that the amount of stearic acid is 0.07 kg and the amount of glyceryl monostearate is 0.03 kg. All other steps are exactly the same as in Example 2. Example

[0042] The method is an adjustment based on Example 2, except that the amount of stearic acid is 0.14 kg and the amount of glyceryl monostearate is 0.06 kg. All other steps are exactly the same as in Example 2. Example

[0043] The method is an adjustment based on Example 2, except that the amount of stearic acid is 0.21 kg and the amount of glyceryl monostearate is 0.09 kg. All other steps are exactly the same as in Example 2.

[0044] Comparative Example 1 The method is based on Example 2, but with adjustments. The difference is that glyceryl betaine is used instead of the mixture of stearic acid and glyceryl monostearate in Example 2, and the amount of glyceryl betaine used is 0.05 kg. The other steps are exactly the same as in Example 2.

[0045] Comparative Example 2 This example is an adjustment based on Example 2, except that glyceryl monostearate is not added, and the amount of stearic acid used is 0.05 kg. All other steps are exactly the same as in Example 2.

[0046] Comparative Example 3 This example is an adjustment based on Example 2, except that stearic acid is not added and the amount of glyceryl monostearate is 0.05 kg. All other steps are exactly the same as in Example 2.

[0047] Comparative Example 4 The following adjustments were made to Example 2, the difference being that Panax notoginseng total saponin powder was used instead of Panax notoginseng total saponin granules, and the amount of Panax notoginseng total saponin powder was 0.1 kg. All other steps were exactly the same as in Example 2.

[0048] Comparative Example 5 This is an adjustment based on Example 2, except that the heater temperature is 90°C. All other steps are exactly the same as in Example 2.

[0049] Comparative Example 6 The method is an adjustment based on Example 2, except that the fan frequency is 25Hz. All other steps are exactly the same as in Example 2.

[0050] Comparative Example 7 Flavoring agents, additives, and Panax notoginseng total saponins granules are used as raw materials. After passing through a 60-mesh sieve, they are thoroughly mixed and then directly granulated. The amount of Panax notoginseng total saponins granules is 0.1 kg, blackcurrant flavoring is 0.02 kg, xanthan gum is 0.015 kg, and sucrose is 2.4 kg.

[0051] III. Specific Experiments of In Vitro Analytical Methods 1. Masking effect on bitterness Level 0 - No bitterness; Level 1 - Bitterness can be felt; Level 2 - Noticeable bitterness; Level 3 - Significantly bitter and difficult to swallow; Level 4 - Strong bitterness, will cause immediate spitting out; Level 5 - Extremely bitter, will cause vomiting.

[0052] The study selected 60 healthy adults aged 20-40 as subjects for statistical analysis.

[0053] The subjects first rinsed their mouths with warm water, then tasted each sample in turn, chewing the sample in their mouths for 20 seconds, immediately selecting the level of bitterness, spitting it out, rinsing their mouths with warm water until there was no taste of that sample in their mouths, and then trying the next sample in turn, until all samples had been tried.

[0054] Table 1 Bitterness level, number of people, sample number Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 0 -- No bitterness 0 0 0 0 0 0 0 0 0 0 0 0 0 1--Able to taste bitterness 13 17 20 19 10 17 0 0 0 0 10 8 0 2--Has a distinctly bitter taste 37 30 35 30 30 30 7 17 17 5 17 11 0 3--The bitter taste is so strong that it is difficult to swallow. 10 13 5 11 20 13 50 13 43 28 10 10 0 4-- Strong bitter taste, spit it out immediately. 0 0 0 0 0 0 10 25 10 27 33 41 0 5--Extremely bitter, causing vomiting 0 0 0 0 0 0 0 0 0 0 0 0 60 Total number of people 60 60 60 60 60 60 60 60 60 60 60 60 60 As can be seen from Table 1: (1) From the results of Examples 2-7, all examples used stearic acid and glyceryl monostearate as hot melt materials. Table 1 shows that none of the examples showed "0 level no bitterness", "4 level strong bitterness requiring immediate spitting" and "5 level extremely bitterness". All subjects were concentrated in level 1 and 2, and a few reported level 3 bitterness. Among them, Example 4 (0.035 kg stearic acid, 0.015 kg glyceryl monostearate, melting temperature 65°C) had the best effect, with 20 people reaching level 1 bitterness and only 5 people reaching level 3 bitterness. Even in Example 7 (total amount of compound material 0.3 kg), only 13 people reached level 3 bitterness and no strong bitterness was observed. This indicates that the combination of "stearic acid + glyceryl monostearate compound material + pre-granulation + suitable process parameters" can achieve a stable and good taste masking effect regardless of how the ratio and total amount of the two are adjusted within a reasonable range. Stearic acid ensures the density of the coating, while glyceryl monostearate improves the fluidity and melting characteristics, which can give full play to the synergistic effect of the compound material and effectively avoid the defects of single materials.

[0055] (2) Comparing Examples 2-7 with Comparative Examples 1-3 (single hot-melt material groups), the advantages of the compound material are clearly evident. Comparative Examples 1-3 used glyceryl betaine, pure stearic acid, and pure glyceryl monostearate to replace the compound material, respectively, with other conditions consistent with Example 2. The bitterness levels of these three comparative examples in Table 1 were significantly increased: Comparative Example 1 (glyceryl betaine) had 50 people with a level 3 bitterness and 10 people with a level 4 bitterness; Comparative Example 2 (pure stearic acid) had 13 people with a level 3 bitterness and 25 people with a level 4 bitterness; Comparative Example 3 (pure glyceryl monostearate) had 43 people with a level 3 bitterness and 10 people with a level 4 bitterness. These results are all much higher than those of the examples. This indicates that single hot-melt materials have limitations due to their characteristics. Glyceryl betaine has uneven coating, pure stearic acid has poor fluidity, and pure glyceryl monostearate has a loose coating layer, which cannot effectively isolate the total saponins of Panax notoginseng from contact with the taste buds. The compound material completely solves this problem through complementary components.

[0056] (3) The comparison between Comparative Example 4, which uses Panax notoginseng total saponin powder instead of pre-granules, and Example 2 verifies the necessity of constructing pre-granules. Comparative Example 4 only changed the raw material from the pre-granules of Example 1 to powder, while the other processes were the same as in Example 2. However, Table 1 shows that its bitterness level increased significantly. This is because powder has a large specific surface area and is prone to agglomeration, which makes it impossible for the compound material to be uniformly coated, and some Panax notoginseng total saponins are directly exposed, causing a strong bitterness. On the other hand, the rounded particles formed by pre-granules can make the molten material spread evenly, avoiding agglomeration and coating gaps. This also confirms the core value of preparing pre-granules in Example 1.

[0057] (4) In Comparative Example 5, the heater temperature was 90℃. The temperature was too low, making it difficult for the hot-melt material to melt, resulting in poor coating effect and large and uneven particle size of the prepared hot-melt particles. In actual production, this could easily lead to problems such as excessively rapid cooling and nozzle blockage. Although granulation was possible in the early stages, once nozzle blockage occurred, the total saponins of Panax notoginseng could not be further sprayed and granulated. Some hot-melt particles of total saponins of Panax notoginseng were prepared, and the compound material could not uniformly coat the total saponins of Panax notoginseng, thus affecting the masking effect. In Comparative Example 6, the fan frequency was 25Hz, which was too low. This could easily lead to poor fluidization, resulting in bed collapse and adhesion to the wall. Although granulation was possible in the early stages, it would cause disordered material fluidization and uneven coating. The masking effect of the prepared hot-melt particles was also poor, and the equipment would not be able to operate normally in the later stages, making further spraying and granulation impossible. This shows that a suitable heater temperature is the key to ensuring sufficient melting of the material, and a reasonable fan frequency is the prerequisite for ensuring uniform coating. The two together support the synergistic effect of the compound material and the pre-granules.

[0058] (5) Comparative Example 7 uses the traditional process, namely: traditional flavoring + sugar masking treatment. It can be seen that this treatment method cannot completely cover up the bitterness. However, none of the samples reached level 5 bitterness, and there was not even level 4 bitterness. This proves that the root-caking effect of hot melt coating through physical barriers is far superior to the taste masking of traditional flavoring. Moreover, it does not require the addition of a large amount of sweetener, which is more in line with the quality requirements of pharmaceuticals.

[0059] 2. Electronic tongue testing procedure The electronic tongue used in this invention was obtained commercially. After activation, calibration, and diagnostic testing at room temperature, the electronic tongue was precisely weighed as test samples from the examples and comparative examples. The test sample contained 1.000 g of total Panax notoginseng saponins, which was added to 100 mL of distilled water and sonicated at 60°C for 10 min. The supernatant was then directly tested. The electronic tongue was sampled for 120 s, with 6 samples collected per sample. The washing time was 10 s. Data spectral analysis was then performed (e.g.,...). Figure 1 As shown), a database sample was constructed based on the experimental results. PLSR and SVM analysis methods were selected to establish a linear model, and PCA principal component analysis was performed on the samples (e.g., ...). Figure 2 As shown), to achieve the evaluation of the bitterness of drugs using electronic tongue (e.g. Figure 3 and Figure 4 The same testing methods were used to evaluate the bitterness of the samples prepared in the examples and comparative examples using electronic tongue testing.

[0060] Figure 1 This is an electronic tongue fingerprint signal spectrum of Panax notoginseng total saponins raw material. The lines of different colors in the figure show the signal response changes of the six sensors in the electronic tongue to the Panax notoginseng total saponins raw material sample over 120 seconds. Different sensors exhibit different signal fluctuation characteristics. These characteristic data constitute the sample data analysis library, providing the original signal basis for subsequent evaluation of the bitterness of the drug. Figure 2 The PCA principal component analysis results are shown in the figure, visually presenting the distribution of different samples in the principal component space. The clustering of Panax notoginseng total saponin granules and inclusion materials under different mass ratios (e.g., inclusion material mass accounting for 25%, 50%, and 75% of the total Panax notoginseng saponin granule mass) and purified water samples is clearly separated, while samples of the same category (same or similar total Panax notoginseng saponin content) cluster together. This indicates that the electronic tongue combined with PCA principal component analysis can effectively distinguish different samples, providing data support for the evaluation of the bitterness of Panax notoginseng total saponin hot-melt granules, and demonstrating the effectiveness of the analytical model built based on this electronic tongue in sample differentiation. The electronic tongue collects bitterness signal characteristics of Panax notoginseng total saponin raw material samples, samples obtained under different mass ratios of Panax notoginseng total saponin granules and inclusion materials (e.g., inclusion material mass accounting for 25%, 50%, and 75% of the total Panax notoginseng saponin granule mass), and pure water through multiple sensors. Based on these, MVR (Multivariate Regression) models and SVM (Support Vector Machine) models are constructed to evaluate bitterness. Figure 3 As shown, the training regression R of the MVR model 2 The result of 0.9992 indicates that the signal collected by the electronic tongue in this invention, after being modeled by MVR, has a very high degree of fit between the predicted value and the true value. The model has excellent prediction accuracy and can accurately reflect the bitterness-related characteristics of the sample. Figure 4 As shown, the SVM model output prediction result is 0.7040, which can be used to evaluate the performance of the SVM model in the bitterness evaluation task based on electronic tongue signals, providing a quantitative reference for model performance. These results demonstrate that electronic tongue combined with modeling methods such as MVR and SVM can effectively perform quantitative analysis and prediction of the bitterness of Panax notoginseng total saponins hot-melt particles, providing a reliable technical path for drug bitterness evaluation.

[0061] Subsequently, using the aforementioned electronic tongue and the constructed model, the masking effect of the example and comparative products was analyzed. The signal fluctuation amplitude near the 0 axis of the example group was significantly smaller than that of the comparative group. The curves of the example group were mostly concentrated in the range of -0.5 to 2.5, without extreme peaks; while the curves of the comparative group frequently showed large fluctuations of -2 to 4, which corresponded perfectly to the bitterness level data in Table 1. The smaller the fluctuation, the less bitter substances the sample released, and the better the masking effect.

[0062] 3. Dissolution test Dissolution test: 0.125 g of the Panax notoginseng total saponins hot-melt granules prepared in the examples and comparative examples were weighed out respectively, and the dissolution rate was tested according to the method for determining the dissolution rate of Panax notoginseng total saponins in the 35th edition of the United States Pharmacopeia. The medium was 900 mL of pH 7.0 phosphate buffer (3.7g sodium dihydrogen phosphate and 5.7g anhydrous disodium hydrogen phosphate were dissolved in 1000 mL of water). Rotation speed: 50 rpm. Test solution temperature: 37 ± 0.5℃. UV detection wavelength: 280 nm.

[0063] The hot-melt particles of Panax notoginseng total saponins prepared in the examples gradually dissolve due to the hydrophilicity of glyceryl monostearate, resulting in a slow release of Panax notoginseng total saponins. The dissolution rate is ≥60% at 30 min (meeting the requirements of the United States Pharmacopeia) and ≥85% at 120 min, with a stable dissolution curve. This is because the hydrophobicity of stearic acid in the compound material can delay the initial release, while the hydrophilicity of glyceryl monostearate can promote the later dissolution, achieving a two-phase release. This not only avoids the bitterness caused by rapid release in the mouth and ensures taste masking, but also meets the needs of effective intestinal absorption. Comparative Example 1 showed uneven coating, with some particles dissolving rapidly while others agglomerated and remained insoluble, resulting in significant differences in dissolution rates at 30 min. Comparative Example 2 exhibited excessive hydrophobicity, leading to slow dissolution and a dissolution rate of <40% at 30 min, impacting bioavailability. Comparative Example 3 showed a loose coating layer, resulting in rapid initial dissolution and a dissolution rate >80% at 30 min; however, due to the lack of dense coating, the masking effect was poor, consistent with the high bitterness level results in Table 1. Comparative Example 4 showed uneven coating due to direct hot melting of the powder, causing rapid disintegration of agglomerated particles during dissolution, resulting in a dissolution rate >90% at 30 min; however, due to the lack of effective coating, bitter substances were released simultaneously, consistent with the high proportion of level 4 bitterness in Table 1. Comparative Examples 5-6 showed coating layer defects due to insufficient heater temperature or excessively low fan frequency, resulting in rapid drug leakage during dissolution, with a dissolution rate >80% at 30 min and large fluctuations in the dissolution curve. Comparative Example 7 used traditional flavoring to mask the taste, without heat-melting coating, relying solely on physical mixing. The total saponins of Panax notoginseng dissolved rapidly in the intestinal environment, with a dissolution rate of >95% in 30 minutes, and the taste masking failed.

[0064] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit the technical solutions. Those skilled in the art should understand that any modifications or equivalent substitutions to the technical solutions of the present invention without departing from the spirit and scope of the present invention should be covered within the scope of the claims of the present invention.

Claims

1. A method for masking the taste of total saponins from Panax notoginseng, characterized in that, The specific steps are as follows: Step 1: Add the total saponins of Panax notoginseng granules and the inclusion material into a hot melt spray granulation fluidized bed to prepare hot melt microparticles; wherein, the hot melt temperature is 65℃-120℃, the atomization pressure is 0.3MPa-0.5MPa, and the mass ratio of total saponins of Panax notoginseng granules to inclusion material is 1:(0.5-3). Step 2: Pass the hot-melt microparticles prepared in Step 1 through a 50-mesh sieve and a 65-mesh sieve respectively, and collect the intermediate particles of 50-65 mesh.

2. The processing method according to claim 1, characterized in that, In step 1, the inclusion material is composed of stearic acid and glyceryl monostearate, with a mass ratio of stearic acid to glyceryl monostearate of (5-7):(3-5).

3. The processing method according to claim 1, characterized in that, In step 1, the fan frequency is 35Hz-40Hz.

4. The processing method according to claim 1, characterized in that, In step 1, the temperature during granulation is maintained at 65℃-75℃.

5. The processing method according to claim 1, characterized in that, In step 1, the total saponins of Panax notoginseng granules are obtained through the following steps: S1: Mix total saponins of Panax notoginseng, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and lactose; wherein the mass ratio of total saponins of Panax notoginseng, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and lactose is 63:50:50:

153. S2: Add the mixed material from S1 into a spray granulator. Spray granulation is performed using a peristaltic pump with a povidone K30 aqueous solution. Spray granulation is carried out under the conditions of atomization pressure of 0.45~0.62 bar, inlet air temperature of 44~50℃, and peristaltic pump speed of 35~85 rpm to prepare Panax notoginseng total saponin granules. The concentration of povidone K30 in the povidone K30 aqueous solution is 8 wt%, and the mass ratio of Panax notoginseng total saponins to povidone K30 aqueous solution is 52:50.

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