Sargassum pallidum polypeptide chewable tablet and preparation method thereof
By preparing chewable tablets containing seaweed peptides and specific excipients, the lack of standardization of seaweed peptide chewable tablets has been solved, resulting in chewable tablet products with stable quality and good taste, and promoting the high-value utilization of seaweed peptides.
Patent Information
- Application Number
- CN202511406126.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-23
- Publication Date
- 2025-11-18
AI Technical Summary
In the current technology, Artemisia annua polypeptide has not yet been developed into a standardized chewable tablet formulation, and there is a lack of systematic research and related products.
A chewable tablet with a hardness of 3-8 kg was prepared using a composition of 30% seaweed polypeptide, 42%-62% isomaltitol, 3.75%-23.75% maltodextrin, 2%-4% povidone K30, 0.7%-1% magnesium stearate, and 0.25% flavoring. The raw materials were screened through a 60-100 mesh screen, and purified water, 50% ethanol, or 70% ethanol were used as wetting agents. The preparation method included mixing, drying, and tableting.
We have developed a chewable tablet containing seaweed peptides with controllable quality and good taste, which meets the requirements for hardness and disintegration time of chewable tablets, thereby enhancing the high-value utilization and market application prospects of seaweed peptides.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical preparation technology, specifically to a seaweed polypeptide chewable tablet and its preparation method. Background Technology
[0002] Sargassum pallidum is a common marine brown algae widely distributed along the coast of my country, with a long history of medicinal and edible use. Modern research shows that Sargassum pallidum is rich in various bioactive components, including polysaccharides, polypeptides, polyphenols, and minerals, possessing multiple physiological functions such as antioxidation, antitumor activity, immunomodulation, and lipid-lowering effects. Among these, Sargassum pallidum polypeptides, as one of its important active ingredients, have received widespread attention in recent years due to their small molecular weight, easy absorption, and high bioavailability.
[0003] Chewable tablets, as a common oral solid dosage form, have advantages such as convenient administration, pleasant taste, and no need for water, making them particularly suitable for children, the elderly, and patients with swallowing difficulties. Compared to regular tablets, chewable tablets have special requirements in terms of formulation process and quality control, such as needing to have appropriate hardness, a good taste, and a short disintegration time to ensure medication safety and patient compliance.
[0004] Currently, research on the active ingredients of Artemisia capillaris mainly focuses on extraction processes, activity evaluation, and the application of crude extracts, while research on its further development into standardized and regulated formulations remains relatively limited. In particular, there is a lack of systematic research and the emergence of related products for chewable tablet formulations with Artemisia capillaris polypeptides as the main active ingredient.
[0005] This invention provides a seaweed polypeptide chewable tablet with a reasonable formula, stable process, controllable quality, and good taste. It not only helps to promote the high-value utilization of seaweed, but also provides new directions and technical support for the development of marine-derived functional foods and medicines. Summary of the Invention
[0006] The technical problem to be solved by the present invention is to address the shortcomings of the prior art by providing a chewable tablet of Artemisia annua polypeptide and its preparation method.
[0007] To achieve the objectives of this invention, the following technical means are specifically employed:
[0008] A chewable tablet containing seaweed polypeptide is characterized by comprising the following components in weight percentage: 30% seaweed polypeptide, 42%–62% isomaltitol, 3.75%–23.75% maltodextrin, 2%–4% povidone K3O, 0.7%–1% magnesium stearate, and 0.25% flavoring; the sum of the weight percentages of all components is 100%.
[0009] The aforementioned Artemisia annua polypeptide chewable tablet is characterized in that the hardness of the chewable tablet is 3-8 kg.
[0010] The aforementioned Artemisia annua polypeptide chewable tablet is characterized in that the raw material of the Artemisia annua polypeptide has a particle size that passes through a 60-100 mesh sieve.
[0011] The method for preparing the Artemisia annua polypeptide chewable tablets is characterized by comprising the following steps:
[0012] (1) Pass the seaweed polypeptide through a 60-100 mesh sieve, and pass isomaltitol and maltodextrin through an 80 mesh sieve respectively, for later use;
[0013] (2) Weigh out the seaweed polypeptide, isomaltitol, maltodextrin and povidone K30 after step (1) according to the prescription amount, and mix them evenly.
[0014] (3) Add a wetting agent to the mixture in step (2) to make a soft material, and pass the soft material through a 20-mesh sieve to make wet granules;
[0015] (4) Dry the wet granules at 50°C until the moisture content does not exceed 3%, cool them, and then pass them through a 20-mesh sieve for granulation.
[0016] (5) Add the prescribed amount of magnesium stearate and flavoring to the dry granules from step (4) and mix well;
[0017] (6) Compress the final mixture from step (5) into tablets to obtain the final product.
[0018] The preparation method is characterized in that the wetting agent in step (3) is purified water, 50% ethanol or 70% ethanol.
[0019] The seaweed polypeptide described in this invention is an off-white powder with a particle size standard of 100% passing through an 80-mesh sieve, a peptide content (on a dry basis) ≥99%, a molecular weight ≤1000 Da, a loss on drying ≤5.0%, an ash content ≤5.0%, pesticide residues not detectable, total heavy metals ≤10 ppm, arsenic content ≤10 ppm, lead content ≤10 ppm, total bacterial count ≤1000 cfu / g, yeast and mold ≤100 cfu / g, Escherichia coli not detectable, Salmonella not detectable, and Staphylococcus not detectable.
[0020] Beneficial effects
[0021] This invention provides a chewable tablet product containing seaweed polypeptides that has both good taste and stability. It also identifies the preparation process and quality control methods, providing a practical and feasible path for the in-depth development and high-value utilization of seaweed polypeptides, and has good market application prospects. Detailed Implementation
[0022] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the present invention or its application or use. 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.
[0023] The following is a description of the Artemisia annua polypeptide used in this invention: The manufacturer is Xi'an Muguo Biotechnology Co., Ltd., product batch number: MG-2024081502. It is an off-white powder with a particle size standard of 100% passing through an 80-mesh sieve. The peptide content (on a dry basis) is 99.07%, molecular weight ≤1000 Da, loss on drying is 0.79%, ash content is 1.42%, pesticide residues were not detected, total heavy metals ≤10 ppm, arsenic content ≤10 ppm, lead content ≤10 ppm, total bacterial count ≤1000 cfu / g, yeast and mold ≤100 cfu / g, Escherichia coli, Salmonella, and Staphylococcus were not detected.
[0024] Example 1
[0025] 1. The preliminary prescription is as follows:
[0026] Element effect Proportion(%) Artemisia annua polypeptide Main drug 30％ Isomaltitol filler 52％ maltodextrin filler 13.75％ Povidone K30 adhesives 3％ magnesium stearate lubricant 1％ essence Flavoring agents 0.25％
[0027] 2. The preliminary preparation process is as follows:
[0028] Seaweed polypeptide, isomaltitol, and maltodextrin were each passed through an 80-mesh sieve. The corresponding ingredients were accurately weighed according to the prescription. The seaweed polypeptide, isomaltitol, maltodextrin, and povidone K30 were mixed evenly, and purified water was added to granulate until the soft material reached a state where it "could be formed into a ball when squeezed by hand, but crumbled easily when touched." The soft material was passed through a 20-mesh sieve to obtain wet granules, which were then transferred to an electric heating drying oven at 50°C and dried until the moisture content did not exceed 3%. After cooling to room temperature, the granules were sieved through a 20-mesh sieve for granulation. Then, the prescribed amounts of magnesium stearate and flavoring were added and mixed evenly. A 6.0mm shallow concave die was used to press the tablets, with a target tablet weight of 120mg and a target hardness of 5-6kg. The tablets were then compressed to obtain seaweed polypeptide chewable tablets.
[0029] 3. The calculation and measurement methods for some evaluation indicators are as follows:
[0030] 3.1 Angle of repose
[0031] The angle of repose of the particles was measured using the BT-1001 intelligent powder property tester from Dandong Better Instruments Co., Ltd., as a characterization of particle flowability.
[0032] 3.2 Disintegration Time Limit
[0033] The "Technical Guidelines for Quality Attribute Research of Chewable Tablets (Chemical Drugs) (Trial)" (No. 7, 2023) issued by the Center for Drug Evaluation of the National Medical Products Administration requires that "to avoid gastrointestinal obstruction caused by patients swallowing whole or not chewing completely, the disintegration time of chewable tablets should be studied, and it is recommended to conduct the study according to the 'Disintegration Time Test Method' in General Chapter IV of the Chinese Pharmacopoeia. Unless otherwise specified, it should meet the disintegration time requirements for oral ordinary tablets in the Chinese Pharmacopoeia." This invention, based on the "Disintegration Time Test Method" in the 2020 edition of the Chinese Pharmacopoeia, uses a lift-type disintegration apparatus to examine the disintegration time of samples.
[0034] 3.3 Sensory Evaluation Criteria
[0035] The sensory evaluation of the product was conducted according to the standards in the table below, with a maximum score of 54 points. Ten healthy volunteers aged 20-30 were selected for the evaluation.
[0036]
[0037] Example 2: Screening Study of Prescription Composition
[0038] 1. Screening of wetting agent types
[0039] Purified water, 50% ethanol, and 70% ethanol were selected as wetting agents for evaluation. Each material was weighed according to the initial formulation, and three groups of samples were prepared according to the preliminary proposed preparation process. The difference lay in the use of different wetting agents for granulation. The granulation endpoint for all three groups was "forming a clump when squeezed in the hand, but crumbling easily upon light touch." The target tablet weight and the same tablet hardness range were controlled for all three groups. The wetting agent was selected by comparing the total particle repose angle, disintegration time, and sensory scores of the three groups. The experimental results are shown in Table 1 below.
[0040] Table 1 Results of the screening of wetting agent types
[0041] wetting agent Angle of repose of total mixed particles Disintegration timeout (seconds) Sensory rating Purified water 11.91° 438 52 50% ethanol 20.12° 449 48 70% ethanol 19.26° 360 46
[0042] The results in the table above show that when purified water, 50% ethanol, and 70% ethanol were used as wetting agents, the total particle flowability of the prepared samples was excellent (angle of repose < 30°), the disintegration time met the requirements of the 2020 edition of the Chinese Pharmacopoeia, and the sensory scores were all high. Therefore, purified water, 50% ethanol, and 70% ethanol can all be used as wetting agents in the preparation of this product. Purified water will be temporarily selected as the wetting agent for further investigation.
[0043] 2. Screening of filler dosage
[0044] Purified water was used as the wetting agent. This experiment investigated the effect of isomaltitol addition on the product. Keeping the total amount of isomaltitol and maltodextrin in the formulation constant at 65.75%, the effects of isomaltitol dosages of 42%, 52%, and 62% on the product were investigated. The types and amounts of other materials in the formulation remained the same as the initially proposed formulation, and the preparation method was the same as the initially proposed preparation process. The target tablet weight and the same tablet hardness range were controlled for the three groups of samples. The filler dosage was screened by comparing the total particle repose angle, disintegration time, and sensory scores of the three groups of samples. The experimental results are shown in Table 2 below.
[0045] Table 2. Results of the screening study on filler dosage
[0046] Filler dosage Angle of repose of total mixed particles Disintegration timeout (seconds) Sensory rating 42％ 11.26° 388 52 52％ 15.50° 466 48 62％ 14.97° 320 44
[0047] The results in the table above show that when the filler isomaltitol content was 42%, 52%, and 62%, the total particle flowability of the prepared samples was excellent (angle of repose <30°), the disintegration time met the requirements of the 2020 edition of the Chinese Pharmacopoeia, and the sensory scores were high. Therefore, the formulation dosages of isomaltitol of 42%, 52%, and 62% all meet the preparation requirements of this product. For now, a formulation dosage of 52% isomaltitol will be selected for further investigation.
[0048] 3. Adhesive dosage screening
[0049] Purified water was used as the wetting agent, and isomalt was used at 52% of the formulation. The effect of different amounts of binder on the product was investigated. The binder addition amounts were 2%, 3%, and 4%, respectively. The types and amounts of other materials in the formulation were the same as the initially proposed formulation, and the preparation method was the same as the initially proposed preparation process. The same target tablet weight and the same tablet hardness range were controlled for the three groups of samples. The amount of binder was screened by comparing the total particle repose angle, disintegration time, and sensory scores of the three groups of samples. The experimental results are shown in Table 3 below.
[0050] Table 3. Screening results for adhesive dosage
[0051] Adhesive dosage Angle of repose of total mixed particles Disintegration timeout (seconds) Sensory rating 2％ 13.08° 360 48 3％ 11.26° 388 48 4％ 14.12° 410 44
[0052] The results in the table above show that when the binder dosage was 2%, 3%, and 4%, the total particle flowability of the prepared samples was excellent (angle of repose <30°), the disintegration time met the requirements of the 2020 edition of the Chinese Pharmacopoeia, and the sensory scores were high. Therefore, a binder dosage range of 2%-4% meets the preparation requirements of this product. A binder dosage of 3% is tentatively selected for further investigation.
[0053] 4. Screening of Lubricant Dosage
[0054] Purified water was used as the wetting agent, isomalt was used at 52%, and the binder was used at 3%. The effects of different lubricant additions (0.4%, 0.7%, and 1%) on the product were investigated. The types and amounts of other materials in the formulation were the same as in the preliminary formulation, and the preparation method was the same as in the preliminary preparation process. The same target tablet weight and the same tablet hardness range were controlled for the three groups of samples. The amount of lubricant was screened by comparing the total particle repose angle, disintegration time, and tablet compressibility of the three groups of samples. The experimental results are shown in Table 4 below.
[0055] Table 4 Results of Lubricant Dosage Screening
[0056] Lubricant dosage Angle of repose of total mixed particles Disintegration timeout (seconds) Tablet compressibility 0.4％ 11.87° 312 Difference 0.7％ 13.64° 320 good 1％ 13.97° 388 good
[0057] The results in the table above show that when the lubricant dosage is 0.7% and 1%, the total particle flowability of the prepared samples is excellent (angle of repose <30°), the disintegration time meets the requirements of the 2020 edition of the Chinese Pharmacopoeia, and the tablets have good compressibility. Therefore, the range of magnesium stearate dosage for this product is 0.7%-1%. We have tentatively selected a magnesium stearate dosage of 1% for further investigation.
[0058] Example 3: Screening Study of Preparation Process
[0059] 1. Study on particle size screening of Artemisia annua polypeptide raw materials
[0060] Purified water was used as the wetting agent, isomalt was used at 52%, binder at 3%, and lubricant at 1%. The effect of the particle size of the *Artemisia annua* polypeptide raw material on the product was investigated. The *Artemisia annua* polypeptide raw material was sieved through 60, 80, and 100 mesh sieves for later use. The types and amounts of other materials in the formulation were the same as the initially proposed formulation, and the preparation method was the same as the initially proposed preparation process. The target tablet weight and the same tablet hardness range were controlled for the three groups of samples. The particle size of the *Artemisia annua* polypeptide raw material was screened by comparing the total particle repose angle and disintegration time of the three groups of samples. The experimental results are shown in Table 5 below.
[0061] Table 5. Results of particle size screening of Artemisia annua polypeptide raw materials
[0062] Raw material particle size Angle of repose of total mixed particles Disintegration timeout (seconds) 60 mesh sieve 13.23° 459 80 mesh sieve 11.58° 468 100 mesh sieve 12.11° 381
[0063] The results in the table above show that the total particle flowability of the *Artemisia capillaris* polypeptide raw materials after passing through 60-mesh, 80-mesh, and 100-mesh sieves was excellent (angle of repose < 30°), and the disintegration time met the requirements of the 2020 edition of the *Chinese Pharmacopoeia*. This indicates that the raw materials obtained after passing through 60-100 mesh sieves can be used for the preparation of this product. The *Artemisia capillaris* polypeptide purchased by our research institute has a particle size standard of 100% passing through an 80-mesh sieve. The measured values of the total particle repose angle and disintegration time after passing through 60-mesh and 80-mesh sieves were basically consistent, indicating that no obvious particle aggregation occurred during our use of the *Artemisia capillaris* polypeptide raw materials. We will temporarily choose to pass the *Artemisia capillaris* polypeptide raw materials through a 100-mesh sieve for subsequent research.
[0064] 2. Study on the screening of tablet hardness range
[0065] Purified water was used as the wetting agent, isomalt was used at 52%, binder at 3%, and lubricant at 1%. Artemisia annua polypeptide raw material was sieved through a 100-mesh sieve. The effect of tablet hardness on the product was investigated. The "Technical Guidelines for Quality Attribute Research of Chewable Tablets (Chemical Drugs) (Trial Implementation)" requires that the average hardness of chewable tablets be controlled below 12 kgf / kp. This experiment investigated the tablet hardness within this range, with tablet hardness set at 3–4 kg, 5–6 kg, and 7–8 kg. The types and amounts of other materials in the formulation were the same as the initially proposed formulation, and the preparation method was the same as the initially proposed preparation process. The same target tablet weight was controlled for the three groups of samples. The appropriate tablet hardness range was screened by comparing the disintegration time of the three groups of samples. The experimental results are shown in Table 6 below.
[0066] Table 6 Results of the study on screening hardness range of tablet compression
[0067] Tablet hardness Disintegration timeout (seconds) 3-4kg 555 5-6kg 373 7-8kg 342
[0068] As shown in the table above, when the tablet hardness range is 3-8 kg, the disintegration time of the prepared product meets the requirements of the 2020 edition of the Chinese Pharmacopoeia. Therefore, the suitable tablet hardness range for this product is 3-8 kg.
[0069] Based on the above research results, the formulation of this product is as follows:
[0070] Element effect Proportion(%) Artemisia annua polypeptide Main drug 30％ Isomaltitol filler 52％ maltodextrin filler 13.75％ Povidone K30 adhesives 3％ magnesium stearate lubricant 1％ essence Flavoring agents 0.25％
[0071] Note: The dosage range of the lubricant magnesium stearate is 0.7%-1%; the dosage range of the adhesive polyvinyl ketone K30 formulation is 2%-4%; in the above preferred embodiment, the total amount of isomaltitol and maltodextrin is 65.75%, of which the dosage range of isomaltitol formulation is 42%-62%; the wetting agents are: purified water, 50% ethanol and 70% ethanol.
[0072] The preparation process of this product is as follows: Seaweed polypeptide is passed through a 60-100 mesh sieve, isomaltitol and maltodextrin are passed through an 80 mesh sieve respectively. The corresponding ingredients are accurately weighed according to the prescription. Seaweed polypeptide, isomaltitol, maltodextrin, and povidone K30 are mixed evenly, and purified water (or 50% ethanol, or 70% ethanol) is added for granulation until the soft material reaches a state where it "can be formed into a clump when squeezed, but crumbles easily when lightly touched." The soft material is passed through a 20 mesh sieve to obtain wet granules, which are then transferred to an electric heating drying oven at 50°C and dried until the moisture content does not exceed 3%. After cooling to room temperature, the granules are sieved through a 20 mesh sieve. Then, the prescribed amounts of magnesium stearate and flavoring are added and mixed evenly. A 6.0mm shallow concave die is used for compression, with a target tablet weight of 120mg and a target hardness of 3-8kg. The tablets are then compressed to obtain seaweed polypeptide chewable tablets.
[0073] Example 4: Quality Evaluation Study
[0074] Based on the optimized prescription and preparation process selected from the above experiments, samples were prepared in batches of 5000 tablets. After tableting, samples were taken for the following tests.
[0075] 1. Appearance
[0076] This product is a pale yellow, round tablet with a smooth surface and uniform color. It has the characteristic odor of the raw material, a slightly sweet taste, and no off-odors.
[0077] 2. Tablet weight difference
[0078] According to the 2020 edition of the Chinese Pharmacopoeia, 20 tablets of Artemisia annua polypeptide chewable tablets were taken, and the total weight was accurately weighed. After obtaining the average tablet weight, the weight of each tablet was accurately weighed. The weight of each tablet was compared with the average tablet weight. According to the table, no more than 2 tablets exceeded the weight difference limit, and no tablet exceeded the limit by more than 1 time.
[0079] Average tablet weight or labeled tablet weight / g Quality variation limit / % Less than 0.30g ±7.5％ 0.30g and above ±5％
[0080] Following the above method, weigh 20 tablets as follows (in grams): 0.1211, 0.1183, 0.1207, 0.1193, 0.1189, 0.1236, 0.1197, 0.1228, 0.1206, 0.1246, 0.1227, 0.1256, 0.1240, 0.1212, 0.1202, 0.1224, 0.1212, 0.1223, 0.1230, 0.1219. Based on the above criteria, the tablet weight variation of this product is acceptable.
[0081] 3. Disintegration time limit
[0082] The disintegration time limit test method is determined according to the 2020 edition of the Chinese Pharmacopoeia, 0921. Take 6 tablets of the test sample and place them in the glass tubes of the above-mentioned basket. Start the disintegration tester and check that each tablet disintegrates completely within 15 minutes.
[0083] According to the above regulations, 6 tablets were randomly sampled, and the disintegration times were 390 seconds, 398 seconds, 380 seconds, 373 seconds, 342 seconds, and 381 seconds, which meet the requirements of the Chinese Pharmacopoeia and the disintegration time limit is qualified.
[0084] 4. Hardness
[0085] The "Technical Guidelines for Quality Attribute Research of Chewable Tablets (Chemical Drugs) (Trial)" recommends that the average hardness be controlled below 12 kgf / kp or 120 N.
[0086] Six tablets of this product were randomly selected, and the relationship between their mass and hardness was determined as follows:
[0087] Weight (g) 0.1230 0.1232 0.1251 0.1233 0.1194 Hardness (N) 43.2 42.6 35.5 35.9 41.7
[0088] The results show that the hardness of all samples is less than 120N.
[0089] 5. Stability Test
[0090] The prepared samples were sealed and packaged, and placed at 40℃±2℃ and relative humidity 75%±5% for 6 months to examine the quality of the products. The results are as follows:
[0091] Time (month) Appearance Moisture (%) Disintegration timeout (seconds) Hardness (N) 0 Smooth and intact 2.38 380 42.2 1 Smooth and intact 2.32 385 44.1 2 Smooth and intact 2.51 397 43.8 3 Smooth and intact 2.45 389 45.7 6 Smooth and intact 2.60 399 43.2
[0092] 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 principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A type of Artemisia annua polypeptide chewable tablet, characterized in that, It is composed of the following components by mass percentage: 30% seaweed polypeptide, 42%–62% isomaltitol, 3.75%–23.75% maltodextrin, 2%–4% povidone K3O, 0.7%–1% magnesium stearate, and 0.25% flavoring; the sum of the mass percentages of the above components is 100%.
2. The Artemisia annua polypeptide chewable tablet as described in claim 1, characterized in that, The hardness of the chewable tablet is 3-8 kg.
3. The Artemisia annua polypeptide chewable tablet as described in claim 1 or 2, characterized in that, The raw material particle size of the Artemisia annua polypeptide is 60-100 mesh.
4. A method for preparing Artemisia annua polypeptide chewable tablets as described in any one of claims 1-3, characterized in that, Includes the following steps: (1) Pass the seaweed polypeptide through a 60-100 mesh sieve, and pass isomaltitol and maltodextrin through an 80 mesh sieve respectively, for later use; (2) Weigh out the seaweed polypeptide, isomaltitol, maltodextrin and povidone K30 after step (1) according to the prescription amount, and mix them evenly. (3) Add a wetting agent to the mixture in step (2) to make a soft material, and pass the soft material through a 20-mesh sieve to make wet granules; (4) Dry the wet granules at 50°C until the moisture content does not exceed 3%, cool them, and then pass them through a 20-mesh sieve for granulation. (5) Add the prescribed amount of magnesium stearate and flavoring to the dry granules from step (4) and mix well; (6) Compress the final mixture from step (5) into tablets to obtain the final product.
5. The method as described in claim 4, characterized in that, The wetting agent mentioned in step (3) is purified water, 50% ethanol or 70% ethanol.