Sargassum pallidum polysaccharide granules as well as preparation method and quality evaluation thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to sargassum pallidum polysaccharide granules as well as a preparation method and quality evaluation thereof. The granules are prepared by a wet granulation process, and the prescription composition and the preparation process are systematically screened and researched. The prescription composition screening comprises screening of types and mixing proportions of filling agents, concentrations of wetting agents, types and dosages of adhesives, types and addition amounts of disintegrating agents and types and addition amounts of flavoring agents; the screening of the preparation process comprises the research on the adding mode of the disintegrating agent, the screening mesh number of sargassum pallidum polysaccharide and the water content after particles are dried. The sargassum pallidum polysaccharide granules prepared by the method are high in forming rate, good in fluidity, good in dissolubility and good in taste, all quality indexes meet the requirements of Chinese Pharmacopoeia 2020 edition, and an efficient, stable and high-patient-compliance dosage form choice is provided for application of sargassum pallidum polysaccharide in the fields of medicines and functional foods.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a sargassum polysaccharide granule and a preparation method and quality evaluation thereof. Background Art

[0002] Sargassum pallidum is an extremely important marine brown algae resource, containing a variety of biologically active ingredients such as polysaccharides, polyphenols, and algin. Among these ingredients, Sargassum pallidum polysaccharides have attracted great attention from the scientific research and industry circles due to their significant pharmacological activities such as antioxidant, immunomodulatory, anti-tumor and hypoglycemic effects, and have shown extremely broad application prospects in the fields of medicine and functional foods.

[0003] However, the current research on polysaccharides from Artemisia seaweed mainly focuses on extraction and purification processes and in vitro activity evaluation. In the field of formulation development, it is still in its infancy, especially the research on dosage forms suitable for large-scale industrial production and convenient for clinical application, which is extremely scarce.

[0004] In the prior art, common preparation forms of polysaccharide components mainly include tablets, capsules or oral solutions. However, each of these traditional dosage forms has obvious limitations. The dissolution rate of traditional tablets in the body is relatively slow, which directly leads to its low bioavailability and makes it difficult to fully exert the pharmacological effects of polysaccharide components; the production process requirements of capsules are relatively high, and various parameters need to be strictly controlled during the production process. For some patients, there is a problem of difficulty in swallowing, which limits its scope of use to a certain extent; although oral solutions have the advantage of being easy to absorb, they have poor stability and are easily affected by environmental factors and deteriorate during storage and transportation. At the same time, they are not convenient to carry, and in order to ensure their quality within the shelf life, preservatives often need to be added, which may cause some safety concerns.

[0005] Granules, as a special dosage form, cleverly combine the dual advantages of high stability of solid preparations and good rapid release of liquid preparations, and can effectively make up for the defects of the above-mentioned traditional dosage forms. It not only has better stability during storage and transportation, but also can dissolve quickly after taking, release the active ingredients, and improve bioavailability. At the same time, the way to take granules is relatively flexible, and it is also more friendly to patients with dysphagia.

[0006] In summary, it has become a top priority to develop an optimized prescription and preparation process for Artemisia marinum polysaccharide granules. By scientifically and systematically screening the types of excipients, accurately determining the proportion of excipients, and optimizing process parameters, the key technical problems faced by polysaccharide granules in the preparation process, such as low molding rate, long dissolution time, and poor taste, can be effectively solved. At the same time, it is necessary to ensure that the prepared product fully meets the quality requirements of the pharmacopoeia, thereby providing an efficient, stable, and highly patient-compliant dosage form option for the clinical application of Artemisia marinum polysaccharides, and promoting the widespread application of Artemisia marinum polysaccharides in the fields of medicine and functional foods. Summary of the invention

[0007] The technical problem to be solved by the present invention is to provide a polysaccharide granule of Artemisia seaweed and a preparation method and quality evaluation thereof in view of the deficiencies of the prior art.

[0008] In order to achieve the purpose of the present invention, the following technical means are specifically adopted:

[0009] A granule of sea wormwood polysaccharide, characterized in that it is composed of the following ingredients by weight percentage: 50% of sea wormwood polysaccharide, 34.8225% of mannitol, 11.6075% of lactose monohydrate, 0.75% of microcrystalline cellulose, 2% of povidone K30, and 0.82% of stevioside; wherein the polysaccharide content of the sea wormwood polysaccharide is ≥50% in terms of glucose, the loss on drying is ≤1%, the residue on ignition is ≤0.2%, the heavy metal is ≤10ppm, the pesticide residue is ≤2ppm, the total bacteria count is <1000CFU / g, the mold and yeast are <100CFU / g, and Salmonella and Escherichia coli shall not be detected.

[0010] The artemisia seaweed polysaccharide granules are characterized in that the weight ratio of mannitol to lactose monohydrate is 3:1.

[0011] The method for preparing the Artemisia seagrass polysaccharide granules is characterized by comprising the following steps:

[0012] (1) passing the polysaccharide of Artemisia seagrass through an 80-mesh sieve, and passing mannitol, lactose monohydrate, microcrystalline cellulose, and steviol glycoside through an 80-mesh sieve respectively for later use;

[0013] (2) Weighing each component in proportion, mixing them evenly, and then adding a wetting agent prepared by dissolving povidone K30 in ethanol to prepare a soft material;

[0014] (3) The soft material is granulated through a 16-mesh sieve, the wet granules are dried at 60° C. to a moisture content of 0-3%, and granulated through a 16-mesh sieve to obtain the product.

[0015] The preparation method is characterized in that the microcrystalline cellulose is added by internal addition, that is, it is evenly mixed with the main drug and other auxiliary materials before granulation.

[0016] The preparation method is characterized in that the ethanol concentration in the wetting agent is 95%.

[0017] The quality evaluation method of the Artemisia seaweed polysaccharide granules is characterized by including the following indicators:

[0018] (1) Appearance: light brown-yellow particles with regular shape, uniform drying and no impurities;

[0019] (2) Forming rate ≥ 85%, repose angle ≤ 40°, melting time ≤ 5 minutes;

[0020] (3) The water content is ≤8.0% and complies with the requirements of the granules in the 2020 edition of the Chinese Pharmacopoeia.

[0021] The sea wormwood polysaccharide described in the present invention is powdery and brown, with a polysaccharide content (calculated as glucose) of ≥50%, a drying loss of ≤1%, an ignition residue of ≤0.2%, heavy metals of ≤10ppm, pesticide residues of ≤2ppm, a total bacteria count of <1000CFU / g, molds and yeasts of <100CFU / g, no salmonella detected, and no Escherichia coli detected.

[0022] Beneficial Effects

[0023] Beneficial effects of the present invention:

[0024] 1. Accurately optimize the prescription and process to comprehensively improve product quality: Through systematic screening of the types, dosages and ratios of excipients such as fillers, binders, disintegrants, flavoring agents, etc., and optimizing the preparation process parameters such as the sieving mesh size of Artemisia seagrass polysaccharide, the method of adding disintegrants, the concentration of wetting agents and the moisture content of particles, the Artemisia seagrass polysaccharide granules have excellent performance in key properties such as forming rate, fluidity, solubility, and taste, and all quality indicators meet the requirements of the 2020 edition of the "Chinese Pharmacopoeia", ensuring stable and reliable product quality.

[0025] 2. Improve product applicability and patient compliance: The determined stevioside as a flavoring agent and its optimal addition amount can effectively improve the taste of the product; the optimized granules have regular shape, are dried evenly, and are free of impurities, which is not only convenient for storage and transportation, but also easy for patients to take, thereby improving patients' acceptance and compliance with Artemisia seaweed polysaccharide products and laying a good foundation for its clinical application and market promotion. DETAILED DESCRIPTION

[0026] The technical solution 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 part of the embodiments of the present invention, rather than all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0027] Description of the sea wormwood polysaccharide used in the present invention: the manufacturer is Shaanxi Mixianer Biotechnology Co., Ltd., the product batch number is: 2024.08.21, the polysaccharide content (calculated as glucose) is 50.1%, the drying loss is 0.54%, the ignition residue is 0.12%, the heavy metal is ≤10ppm, the pesticide residue is ≤2ppm, the total bacteria count is <1000CFU / g, the mold and yeast are <100CFU / g, Salmonella is not detected, and Escherichia coli is not detected.

[0028] Example 1

[0029] 1. The preliminary prescription is as follows:

[0030] Element effect Proportion(%) Artemisia seaweed polysaccharide Main drug 50 Mannitol Fillers 34.8225 Lactose Monohydrate Fillers 11.6075 Microcrystalline Cellulose Disintegrants 0.75 Povidone K30 Adhesives 2 Stevioside Flavoring agents 0.82

[0031] 2. The preliminary preparation process is as follows:

[0032] The granules were prepared by wet granulation. The sea wormwood polysaccharide and auxiliary materials were sieved for use, the corresponding components were accurately weighed according to the prescription amount, the auxiliary materials were added in equal increments to make them evenly mixed with the main drug, the binder was dissolved in 95% ethanol, and then added to the mixture for granulation, and fully stirred until the soft material was formed and reached the state of "holding in a ball and falling apart with a light touch". The soft material was passed through a 16-mesh sieve to obtain wet granules, which were then transferred to an electric hot air drying oven for drying, and after cooling to room temperature, passed through a 16-mesh sieve to obtain whole granules, thus obtaining sea wormwood polysaccharide granules.

[0033] 3. The calculation and measurement methods of some evaluation indicators are as follows:

[0034] 3.1 Forming rate

[0035] Take a certain amount of prepared granules, first pass them through a No. 1 sieve, then through a No. 5 sieve, and calculate according to the following formula:

[0036] Forming rate (%) = (1-m1 / m) × 100

[0037] Where: m is the mass of the weighed particles, g; m1 is the total mass of the particles that cannot pass through the No. 1 sieve and can pass through the No. 5 sieve, g.

[0038] 3.2 Overall Rating

[0039] Comprehensive score = [(molding rate / maximum molding rate) + (minimum angle of repose / angle of repose) + (minimum melting time / melting time)] / 3×100

[0040] 3.3 Solubility

[0041] The test was carried out according to the requirements of the 2020 edition of the Chinese Pharmacopoeia. Take 10g of each test sample, add 200ml of hot water, stir for 5 minutes, and observe immediately. The soluble particles should be completely dissolved or slightly turbid.

[0042] Example 2 Prescription composition screening study

[0043] 1. Filler type screening

[0044] According to the initial prescription, 4 parts of sea wormwood polysaccharide powder were weighed, and the fillers in the initial prescription were replaced with soluble starch, mannitol, dextrin, and lactose monohydrate respectively. The main drug and auxiliary materials were sieved through an 80-mesh sieve, and then the main drug, disintegrant, and flavoring agent were added. After mixing, the binder was dissolved in 95% ethanol as a wetting agent, and the soft material was made according to the standard of "holding into a ball by hand and dispersing by light pressure". The prepared soft material was granulated through a 16-mesh sieve by extrusion, and the sieved particles were placed at 60°C and dried to a moisture content of 0-2%, and then sieved through a 16-mesh sieve. The forming rate, angle of repose, and melting time of the four samples were measured. The comprehensive score of particle forming rate, fluidity (angle of repose) and melting time was used as an evaluation index to select the two fillers with the best comprehensive scores, and the next step of research was carried out on them. The obtained particle forming rate, angle of repose, melting time and comprehensive score are shown in the following table.

[0045] Filler Type Forming rate (%) Angle of repose(°) Melting time (seconds) Comprehensive score (points) Soluble starch 87.7 26.54 66 81.42 Mannitol 92.4 29.97 43 91.49 dextrin 88.4 22.51 55 91.08 Lactose Monohydrate 93.0 22.85 48 96.03

[0046] The four groups of granules prepared were all light brown and yellow with a small amount of powder. After observation, the granules made of soluble starch and dextrin as fillers had precipitation after being melted in heated water.

[0047] From the above table, we can see that the comprehensive score of the granules prepared by selecting lactose monohydrate as the filler is the highest, and the comprehensive score of the granules prepared by selecting mannitol as the filler is the second. Therefore, mannitol and lactose monohydrate are selected as mixed fillers for subsequent investigation.

[0048] 2. Screening of mixed filler ratio

[0049] The main drug and excipients are sieved through an 80-mesh sieve, the binder is dissolved in 95% ethanol as a wetting agent, the mass ratio of mannitol and lactose monohydrate is set to 3:1, 2:1, 1:1, 1:2, 1:3, respectively, and other raw and excipients in the initial prescription are added, mixed and made into a soft material, sieved through a 16-mesh sieve for granulation, and then dried at 60°C to a moisture content of 0-2%, and then sieved through a 16-mesh sieve for granulation. The molding rate, angle of repose and melting time of five samples were measured. The optimal mixed filler ratio was selected by calculating the comprehensive score of particle molding rate, fluidity (angle of repose) and melting time as an evaluation index. The obtained particle molding rate, angle of repose, melting time and comprehensive score are shown in the following table.

[0050] Ratio of mannitol to lactose monohydrate Forming rate (%) Angle of repose(°) Melting time (seconds) Comprehensive score (points) 3：1 90.41 22.45 34 97.06 2：1 89.09 24.76 41 88.27 1：1 89.37 26.14 31 94.91 1：2 88.04 27.36 38 87.00 1：3 84.93 26.20 46 82.34

[0051] The five groups of granules prepared were all light brown granules with a small amount of powder. The comprehensive scores of each ratio group were all high, all > 82 points. According to the comprehensive scores in the above table, the best ratio of filler mixed excipients was screened as mannitol: lactose monohydrate = 3:1.

[0052] 3. Determination of wetting agent concentration

[0053] The main drug and excipients are sieved through an 80-mesh sieve. The ratio of mannitol to lactose monohydrate in the prescription is 3:1. Ethanol with concentrations of 75%, 85%, and 95% is selected as a wetting agent, respectively. The binder is added to the above-mentioned concentrations of ethanol, and the remaining excipients in the initial prescription are weighed, mixed and made into a soft material, granulated through a 16-mesh sieve, and then dried at 60°C to a moisture content of 0-2%, and then sieved through a 16-mesh sieve for whole particles. The molding rate, angle of repose, and melting time of three samples were measured. The optimal ethanol concentration was selected by calculating the comprehensive score of particle molding rate, fluidity (angle of repose) and melting time as an evaluation index. The obtained particle molding rate, angle of repose, melting time and comprehensive score are shown in the following table.

[0054] Ethanol concentration (%) Forming rate (%) Angle of repose(°) Melting time (seconds) Comprehensive score (points) 75 \ \ \ \ 85 98.17 29.91 59 77.51 95 90.41 22.45 34 97.37

[0055] When 75% ethanol was used for preparation, the soft material was stuck together and could not be granulated; the granules prepared by 85% ethanol were black-red granules; the granules prepared by 95% ethanol were light brown-yellow granules. The granules prepared by 85% and 95% ethanol had a small amount of powder. It can be seen that both 85% and 95% ethanol concentrations are usable concentrations.

[0056] According to the comprehensive scores in the above table, ethanol with a concentration of 95% was selected as the best wetting agent.

[0057] 4. Selection of adhesive types

[0058] The main drug and excipients are sieved through an 80-mesh sieve. The ratio of mannitol to lactose monohydrate in the prescription is 3:1. The disintegrant and flavoring agent in the initial prescription are weighed, mixed evenly, and prepared for granulation. The binders are selected as povidone K30 and hydroxypropyl methylcellulose E15, both of which are dissolved in 95% ethanol to make soft materials, granulated through a 16-mesh sieve, and then dried at 60°C to a moisture content of 0-2%, and then sieved through a 16-mesh sieve for whole particles. The forming rate, angle of repose and melting time of the two samples are measured. The best type of binder is selected by calculating the comprehensive score of particle forming rate, fluidity (angle of repose) and melting time as the evaluation index. The obtained particle forming rate, angle of repose, melting time and comprehensive score are shown in the following table.

[0059] Adhesive Type Forming rate (%) Angle of repose(°) Melting time (seconds) Comprehensive score (points) Povidone K30 90.41 22.45 34 100 Hydroxypropyl methylcellulose E15 90.25 24.34 106 74.71

[0060] Hydroxypropyl methylcellulose E15 was selected as the adhesive, and the mixed solution prepared by mixing with an appropriate amount of 95% ethanol solution was very viscous. Both groups of granules were light brown-yellow granules with a small amount of powder. It can be seen that all evaluation indicators of the two groups of samples met the requirements of the 2020 edition of the "Chinese Pharmacopoeia" and both were usable adhesives. According to the comprehensive score in the above table, povidone K30 was selected as the best adhesive.

[0061] 5. Adhesive dosage screening

[0062] The dosage of adhesive prescription was investigated at 2%, 3.5% and 5% respectively. Compared with the initial prescription, the total prescription amount was always 100% by adjusting the amount of filler added. The main drug and excipients were sieved through an 80-mesh sieve. The ratio of mannitol to lactose monohydrate in the prescription was 3:1. Each adhesive was dissolved in 95% ethanol to make a soft material, granulated through a 16-mesh sieve, and then dried at 60°C to a moisture content of 0-2%, and then sieved through a 16-mesh sieve for whole particles. The molding rate, angle of repose and melting time of three samples were measured. The optimal amount of adhesive was selected by calculating the comprehensive score of particle molding rate, fluidity (angle of repose) and melting time as an evaluation index. The obtained particle molding rate, angle of repose, melting time and comprehensive score are shown in the following table.

[0063] Adhesive dosage Forming rate (%) Angle of repose(°) Melting time (seconds) Comprehensive score (points) 2％ 90.41 22.45 34 99.62 3.5％ 90.52 28.74 34 92.36 5％ 91.46 26.32 50 84.43

[0064] During the preparation process, the soft material prepared by the adhesive with a prescription amount of 2% was relatively sticky; the soft material prepared by the adhesive with a prescription amount of 3.5% was very sticky; the soft material prepared by the adhesive with a prescription amount of 5% was very sticky. All three groups of granules were light brown granules with a small amount of powder. The indicators of the samples prepared with various dosages all met the requirements of the 2020 edition of the "Chinese Pharmacopoeia", and all were acceptable dosages of adhesive. According to the comprehensive score in the above table, the best dosage of adhesive prescription was 2%.

[0065] 6. Screening of disintegrant types

[0066] The main drug and excipients are sieved through an 80-mesh sieve. The ratio of mannitol to lactose monohydrate in the prescription is 3:1. The binder is dissolved in 95% ethanol. Microcrystalline cellulose and sodium carboxymethyl starch are selected as disintegrants. Other materials in the prescription are added to make a soft material, sieved through a 16-mesh sieve for granulation, and then dried at 60°C to a moisture content of 0-2%, and then sieved through a 16-mesh sieve for whole particles. The forming rate, angle of repose and melting time of the two samples are measured. The best type of disintegrant is selected by calculating the comprehensive score of particle forming rate, fluidity (angle of repose) and melting time as an evaluation index. The obtained particle forming rate, angle of repose, melting time and comprehensive score are shown in the following table.

[0067] Disintegrant Type Forming rate (%) Angle of repose(°) Melting time (seconds) Comprehensive score (points) Microcrystalline Cellulose 90.41 22.45 34 99.10 Sodium carboxymethyl starch 92.93 27.92 48 83.75

[0068] The two groups of granules prepared were light brown and yellow with a small amount of powder. The indicators of the samples prepared by the two disintegrants were good and both could be selected.

[0069] According to the comprehensive scores in the above table, microcrystalline cellulose is the best choice as a disintegrant.

[0070] 7. Screening of disintegrant addition amount

[0071] According to the optimal proportion of mixed fillers, wetting agent concentration, binder type and disintegrant type selected by the above experiment, only the dosage of disintegrant prescription was changed, and the disintegrant was added to 0.25%, 0.75% and 1.25% of the prescription respectively, and the dosage of filler in the prescription was adjusted synchronously to keep the total amount of the prescription at 100%. The main drug and excipients were sieved through an 80-mesh sieve, the dosage ratio of mannitol to lactose monohydrate in the prescription was 3:1, the binder was dissolved in 95% ethanol, and other materials in the prescription were added to make a soft material, granulated through a 16-mesh sieve, and then dried at 60°C to a moisture content of 0-2%, and then granulated through a 16-mesh sieve. The molding rate, angle of repose and melting time of three samples were measured. The optimal amount of disintegrant addition was selected by calculating the comprehensive score of particle molding rate, fluidity (angle of repose) and melting time as the evaluation index. The obtained particle molding rate, angle of repose, melting time and comprehensive score are shown in the following table.

[0072] Disintegrant addition amount (%) Forming rate (%) Angle of repose(°) Melting time (seconds) Comprehensive score (points) 0.25％ 91.89 28.66 36 78.89 0.75％ 91.38 28.59 21 92.66 1.25％ 90.41 22.45 34 86.72

[0073] The three groups of granules prepared were all light brown granules with a small amount of powder. The indicators of the samples prepared with the three disintegrant additions were all good and all of them could be selected. According to the comprehensive scores in the above table, the best dosage of microcrystalline cellulose was 0.75%.

[0074] 8. Screening of flavoring agents

[0075] According to the prescription of granules, only the type of flavoring agent was changed, and different flavoring agents were added: stevioside, sucrose, and xylitol. Other prescription compositions and preparation methods were based on the best results obtained from the above experiments, and granules were prepared according to the preparation process. The taste score was used as the evaluation index, and the average of the scores of 5 people randomly selected from the laboratory was calculated as the taste score to screen out the best type of flavoring agent.

[0076] Taste rating of flavoring agents: The full score is 100, with 0-50 points for an unacceptable taste that is too sweet, 50-60 points for a sweet taste that is difficult to accept, 60-80 points for a slightly sweet taste that is acceptable, and 80-100 points for a good taste that is acceptable.

[0077] Flavoring agent type Taste score (points) Stevioside 85.67 sucrose 81.33 Xylitol 80

[0078] The three groups of granules prepared were all light brown granules with a small amount of powder. From the screening results, it can be seen that the taste scores of the three flavoring agents all fell into the highest score range and were all acceptable flavoring agents. According to the taste score, stevioside was selected as the best flavoring agent.

[0079] 9. Screening of the amount of flavoring agent added

[0080] After selecting the flavoring agent, only the amount of the flavoring agent added was changed, and 0.41%, 0.615%, 0.82%, 1.025%, and 1.23% of the prescription amount were added respectively, and the filling amount in the prescription was adjusted synchronously to keep the total amount of the prescription at 100%. Other prescription compositions and preparation methods were prepared according to the best results obtained from the above experiments, and the granules were prepared according to the preparation process. The taste score was used as the evaluation index, and the taste score was calculated by randomly selecting 5 people from the laboratory and the average was calculated as the taste score to screen the best amount of flavoring agent added.

[0081] Taste rating of flavoring agents: The full score is 100, with 0-50 points for an unacceptable taste that is too sweet, 50-60 points for a sweet taste that is difficult to accept, 60-80 points for a slightly sweet taste that is acceptable, and 80-100 points for a good taste that is acceptable.

[0082] Flavoring agent added (%) Taste score (points) 0.41 87 0.615 84.25 0.82 89.25 1.025 76.25 1.23 71.25

[0083] The five groups of granules prepared were all light brown granules with a small amount of powder. The scores of the flavoring agent addition amount in the range of 0.41-0.82% all fell within the optimal score range and were all acceptable addition amounts. According to the taste scores in the above table, the addition amount of the flavoring agent stevioside was screened to be 0.82% of the granule mass as the best.

[0084] Example 3 Preparation process screening study

[0085] 1. Study on the method of adding disintegrant

[0086] Internal addition method: sieve the raw and auxiliary materials, weigh each material according to the prescription amount, mix them evenly, dissolve the binder in 95% ethanol to make a soft material, use a 16-mesh sieve to make wet granules, dry the wet granules at 60°C to a moisture content of 0-2%, and then pass through a 16-mesh sieve to make whole granules.

[0087] External addition method: sieve the raw materials and auxiliary materials, weigh each material except microcrystalline cellulose according to the prescription amount, mix them evenly, dissolve the binder in 95% ethanol to make a soft material, use a 16-mesh sieve to make wet granules, dry the wet granules at 60°C to a moisture content of 0-2%, then pass through a 16-mesh sieve to make whole granules, then add microcrystalline cellulose and mix evenly.

[0088] Internal and external addition method: sieve the raw materials and auxiliary materials, mix half of the microcrystalline cellulose with the remaining raw materials and auxiliary materials according to the prescription amount, make soft materials, granulate, dry and granulate, add the other half of the microcrystalline cellulose to the dry granules and mix well.

[0089] The particle formation rate, fluidity (angle of repose) and melting time of the three methods of internal addition, external addition and internal and external addition were investigated respectively, and the comprehensive score was calculated as the evaluation index to select the best disintegrant addition method. The particle formation rate, angle of repose, melting time and comprehensive score obtained are shown in the following table.

[0090] Disintegrant addition method Forming rate (%) Angle of repose(°) Melting time (seconds) Comprehensive score (points) Internal addition 89.70 26.18 9 99.58 Additive method 87.81 25.85 19 81.75 Internal and external addition 89.14 26.73 18 82.03

[0091] The three groups of granules prepared were all light brown granules with a small amount of powder. The indicators of the samples prepared by the three addition methods were all good and acceptable. According to the comprehensive scores in the above table, the internal addition method was the best for selecting the disintegrant addition method.

[0092] 2. Study on the sieve mesh number of Artemisia seaweed polysaccharide

[0093] Take three portions of sea wormwood polysaccharide and pass them through 40 mesh, 60 mesh and 80 mesh sieves respectively, then granulate according to the optimal prescription and method screened out above, and measure the forming rate, repose angle and melting time of the three samples. The best sieve mesh number of sea wormwood polysaccharide is screened by calculating the comprehensive score of particle forming rate, fluidity (repose angle) and melting time as an evaluation index. The obtained particle forming rate, repose angle, melting time and comprehensive score are shown in the following table.

[0094] Screening mesh number Forming rate (%) Angle of repose(°) Melting time (seconds) Comprehensive score (points) 40 mesh 90.55 25.41 32 76.04 60 mesh 90.21 29.64 24 74.28 80 mesh 89.70 26.18 9 98.71

[0095] The three groups of granules prepared were all light brown granules with a small amount of powder. The indicators of the samples prepared with the three sieve mesh sizes were all good and acceptable. According to the comprehensive scores in the above table, the best sieve mesh for selecting Artemisia seagrass polysaccharide was 80 mesh.

[0096] 3. Moisture content of granules after drying

[0097] According to the best method investigated in the above experiment, two identical wet granules were prepared, and dried to a moisture content of 0-2% and 2-3% respectively at the same drying temperature of 60°, and then sieved through a 16-mesh sieve for granulation. The forming rate, angle of repose and solubility of the two samples were measured. The optimal moisture content range of the granules was determined by calculating the comprehensive score of the granule forming rate, fluidity (angle of repose) and melting time as the evaluation index. The obtained granule forming rate, angle of repose, melting time, moisture content and comprehensive score are shown in the following table.

[0098] Water content (%) Forming rate (%) Angle of repose(°) Melting time (seconds) Comprehensive score (points) 2.43 89.81 23.35 27 86.22 1.86 90.36 29.60 16 92.96

[0099] The two groups of granules prepared were both light brown-yellow granules with a small amount of powder.

[0100] According to the comprehensive scoring screening in the above table, when the moisture content of the particles is 0-2% and 2-3%, the particle forming rate, fluidity and melting time are all better. The moisture content range of the particles is set to 0-3%.

[0101] Example 4

[0102] After the above screening research, the best prescription of Artemisia Seaweed Polysaccharide Granules was determined to be:

[0103] Element effect Proportion(%) Artemisia seaweed polysaccharide Main drug 50 Mannitol Fillers 34.8225 Lactose Monohydrate Fillers 11.6075 Microcrystalline Cellulose Disintegrants 0.75 Povidone K30 Adhesives 2 Stevioside Flavoring agents 0.82

[0104] After the above screening research, it was determined that the best preparation method of Artemisia seagrass polysaccharide granules is:

[0105] The raw materials and auxiliary materials are passed through an 80-mesh sieve, the binder is dissolved in 95% ethanol as a wetting agent, and the disintegrant is added by internal addition. The raw materials and auxiliary materials are mixed evenly to prepare a soft material, which is dried at 60°C to a moisture content of 0-3%, and then passed through a 16-mesh sieve to obtain granules.

[0106] Example 5

[0107] According to the best prescription and preparation method screened out in the above experiment, three batches of samples were prepared for quality evaluation.

[0108] 1. Appearance and shape: Observe the granules under natural light and record their color, odor, appearance, impurities, etc.

[0109] (1) Color: light brown.

[0110] (2) Odor: Slight seaweed odor.

[0111] (3) Appearance:

[0112] ① Dryness: The granules of Artemisia seagrass polysaccharide are dry, without moisture absorption, softening, caking, deliquescence, etc.;

[0113] ②Particle uniformity: particle size is uniform and color depth is consistent;

[0114] ③Morphology: The particle shape is regular, most of them are long strips, and a small part is powder.

[0115] (4) Impurities: No obvious visible foreign matter.

[0116] 2. Particle size: Determined according to the requirements of the 2020 edition of the Chinese Pharmacopoeia.

[0117] Take 3 batches of samples and determine the forming rate. The sum of the samples that cannot pass through the No. 1 sieve and the samples that can pass through the No. 5 sieve shall not exceed 15%.

[0118] sample Forming rate (%) 1 89.79 2 87.41 3 88.76

[0119] According to the test results, the sample particle size is qualified.

[0120] 3. Moisture content: Determined in accordance with the requirements of the 2020 edition of the Chinese Pharmacopoeia. Unless otherwise specified, the moisture content shall not exceed 8.0%.

[0121] sample Water content (%) 1 1.38 2 1.26 3 1.93

[0122] According to the test results, the moisture content of the sample is qualified.

[0123] 4. Fluidity: Determined according to the requirements of the 2020 edition of the Chinese Pharmacopoeia.

[0124] sample Angle of repose(°) 1 21.40 2 23.61 3 23.89

[0125] According to the test results, the sample has good fluidity.

[0126] 5. Solubility: Determined according to the requirements of the 2020 edition of the Chinese Pharmacopoeia.

[0127] Take 10g of each test sample, add 200ml of hot water, stir for 5 minutes, and observe immediately. The soluble particles should be completely dissolved or slightly turbid.

[0128] sample Melting time (seconds) 1 12 2 11 3 6

[0129] According to the test results, the solubility of the sample is qualified.

[0130] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A polysaccharide granule of Artemisia seagrass, characterized in that: The invention is composed of the following ingredients by weight percentage: 50% of sea wormwood polysaccharide, 34.8225% of mannitol, 11.6075% of lactose monohydrate, 0.75% of microcrystalline cellulose, 2% of povidone K30 and 0.82% of steviol glycoside; wherein the polysaccharide content of the sea wormwood polysaccharide is ≥50% in terms of glucose, the loss on drying is ≤1%, the residue on ignition is ≤0.2%, the heavy metal is ≤10ppm, the pesticide residue is ≤2ppm, the total bacteria count is <1000CFU / g, the mold and yeast are <100CFU / g, and Salmonella and Escherichia coli shall not be detected.

2. The Artemisia seaweed polysaccharide granules according to claim 1, characterized in that The weight ratio of mannitol to lactose monohydrate is 3:

1.

3. A method for preparing the Artemisia seaweed polysaccharide granules according to claim 1 or 2, characterized in that: The following steps are involved: (1) passing the polysaccharide of Artemisia seagrass through an 80-mesh sieve, and passing mannitol, lactose monohydrate, microcrystalline cellulose, and steviol glycoside through an 80-mesh sieve respectively for later use; (2) Weighing each component in proportion, mixing them evenly, and then adding a wetting agent prepared by dissolving povidone K30 in ethanol to prepare a soft material; (3) The soft material is granulated through a 16-mesh sieve, the wet granules are dried at 60° C. to a moisture content of 0-3%, and granulated through a 16-mesh sieve to obtain the product.

4. The preparation method according to claim 3, characterized in that: The microcrystalline cellulose is added by internal addition method, that is, it is evenly mixed with the main drug and other auxiliary materials before granulation.

5. The preparation method according to claim 3 or 4, characterized in that: The ethanol concentration in the wetting agent is 95%.

6. A method for evaluating the quality of the Artemisia seaweed polysaccharide granules according to claim 1 or 2, characterized in that: Indicators include: (1) Appearance: light brown-yellow particles with regular shape, uniform drying and no impurities; (2) Forming rate ≥ 85%, repose angle ≤ 40°, melting time ≤ 60 seconds; (3) The water content is ≤8.0% and complies with the requirements of the granules in the 2020 edition of the Chinese Pharmacopoeia.

7. Use of the Artemisia seagrass polysaccharide granules according to any one of claims 1 to 6 in the preparation of medicines or functional foods with antioxidant, immunomodulatory, anti-tumor or hypoglycemic functions.