Slow-release solid chewable tablet rich in cistanche phenylethanoid glycoside and preparation method thereof

Abstract

The invention relates to the technical field of medicines, and discloses a sustained-release solid chewable tablet rich in cistanche phenylethanoid glycosides and a preparation method thereof, the sustained-release solid chewable tablet comprises the following components by weight: 15-30% of a cistanche extract, 20-40% of a sustained-release matrix material, 15-35% of a chewable filler, 3-8% of a natural sweetener, 1-3% of a flavoring agent, 0.5-2% of a flow aid, 0.5-1.5% of a lubricant and 0.2-1% of a natural perfume, through a gradient baking technology, phenylethanoid glycoside active ingredients, especially echinacoside and acteoside, in cistanche deserticola are effectively reserved, meanwhile, release of components such as polysaccharide is promoted, the extraction efficiency is improved, through the scientific proportion of composite slow-release matrix materials, the tablets can slowly release the active ingredients in the body, the stable blood concentration is maintained, and the curative effect is good. The medicine action time is prolonged, the medicine taking frequency is reduced, the bitter taste of cistanche deserticola is effectively covered through scientific compatibility of a natural sweetening agent, a flavoring agent and spices, and the medicine taking compliance of a patient is improved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides and its preparation method. Background Technology

[0002] Cistanche deserticola, a plant of the Orobanchaceae family, is known as "desert ginseng" and possesses multiple benefits including tonifying the kidneys and strengthening yang, moistening the intestines and relieving constipation, and delaying aging. Modern pharmacological research shows that the main active ingredients of Cistanche deserticola are phenylethanoid glycosides, which have various pharmacological effects such as improving cardiovascular microcirculation, protecting the nervous system, and enhancing immunity. Currently, existing Cistanche deserticola preparations on the market mainly include decoctions, pills, ordinary tablets, and capsules. These traditional preparations have the following drawbacks: Low utilization rate of active ingredients: Traditional processing methods such as decoction and honey pill preparation result in a high rate of destruction of active ingredients, leading to low bioavailability. Dosage form defects: Existing dosage forms are inconvenient to carry and take, especially for elderly patients and those with difficulty swallowing. Taste problems: Cistanche deserticola itself has a bitter taste, and traditional preparations have a poor taste, affecting patient compliance. Unsatisfactory drug release characteristics: Ordinary preparations cannot maintain a stable blood drug concentration, requiring frequent dosing, which easily causes fluctuations in blood drug concentration and affects efficacy. To address the aforementioned issues, developing a Cistanche deserticola preparation that can both mask the unpleasant taste of the drug and delay its release, thereby improving patient compliance, is of great significance. Chewable tablets are tablets taken by chewing or sucking, making them particularly suitable for the elderly, children, and patients with swallowing difficulties. Sustained-release technology allows the drug to be released slowly in the body, maintaining a stable blood drug concentration and reducing the frequency of dosing.

[0003] However, developing Cistanche deserticola extract into sustained-release chewable tablets faces many technical challenges: First, dried plant extracts are usually highly hygroscopic, which can lead to material clumping and chemical instability; second, plant extracts have poor flowability, affecting tablet weight variation and content uniformity; third, plant extracts have poor compressibility and may lack the necessary binding properties, resulting in tablets that are not hard enough or are brittle; and finally, complex phytochemical components may lead to reduced bioavailability.

[0004] Therefore, we propose a sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides and its preparation method. Summary of the Invention

[0005] The present invention mainly addresses the technical problems existing in the prior art, and provides a sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanol glycosides and its preparation method.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: a sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides, comprising the following components by weight percentage: 15-30% Cistanche deserticola extract, 20-40% sustained-release matrix material, 15-35% chewable filler, 3-8% natural sweetener, 1-3% flavoring agent, 0.5-2% gliding agent, 0.5-1.5% lubricant, and 0.2-1% natural flavoring.

[0007] Preferably, the total phenylethyl glycoside content in the Cistanche deserticola extract is not less than 35%, of which the total content of echinacoside and ergosterol is not less than 20%.

[0008] Preferably, the sustained-release matrix material is a composite sustained-release system composed of hydroxypropyl methylcellulose, sodium alginate and microcrystalline cellulose in a weight ratio of 3-5:1-2:2-4.

[0009] Preferably, the chewable filler is a mixture of mannitol and compressible starch in a weight ratio of 2-4:1, and the natural sweetener is a mixture of maltitol and isomaltitol in a weight ratio of 1:1-2.

[0010] Preferably, the flavoring agent is a composite acidulant composed of citric acid and malic acid in a weight ratio of 2-3:1, the flow aid is micronized silica gel, the lubricant is magnesium stearate, and the natural flavoring is one or a combination of orange, pineapple, or strawberry flavorings.

[0011] A method for preparing a sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides, comprising the above-mentioned sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides, specifically including the following steps: Step 1: Raw material pretreatment: After washing the Cistanche deserticola raw material, cut it into 2-3cm thick slices, spray it with vitamin C solution, and then dry it with hot air at 45-55℃ until the moisture content is ≤8%; Step 2: Gradient baking: The pre-treated Cistanche deserticola slices are baked in three stages of gradient baking. The first stage is at 100-110℃ for 4-6 minutes, the second stage is at 80-90℃ for 15-20 minutes, and the third stage is at 55-65℃ for 8-12 minutes. Step 3: Extract preparation: The Cistanche deserticola slices after gradient baking are pulverized to 50-100 mesh, extracted with ultrasonic-assisted ethanol aqueous solution, concentrated and dried to obtain Cistanche deserticola extract rich in phenylethanoid glycosides. Step 4: Material Mixing: Mix the Cistanche deserticola extract, slow-release matrix material, chewable filler, natural sweetener, flavoring agent and natural flavoring evenly in proportion; Step 5: Granulation and tableting: The mixture is granulated using a wet method, dried, and then granulated. A flow aid and a lubricant are added, and after being mixed evenly, the mixture is compressed into tablets.

[0012] Preferably, the conditions for ultrasonic-assisted extraction in the third step are: ethanol concentration 50-70%, material-to-liquid ratio 1:10-15, ultrasonic power 300-500W, extraction temperature 50-60℃, extraction time 30-45min, and extraction 2-3 times.

[0013] Preferably, in the fifth step, the binder used in wet granulation is a 5-10% polyvinylpyrrolidone K30 ethanol solution, the amount of which is 15-25% of the total weight of the material, the drying temperature is 50-60℃, and the material is dried until the moisture content is ≤3%.

[0014] Preferably, in the fifth step, the tableting pressure is 10-20kN, the tablet weight is 1.0-2.0g / tablet, and the tablet hardness is 40-80N.

[0015] This invention provides a sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides and its preparation method. It has the following beneficial effects: This invention relates to a sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides and its preparation method. Through gradient baking technology, the active phenylethanoid glycosides in Cistanche deserticola, especially echinacoside and ergosterol, are effectively preserved, while the release of polysaccharides and other components is promoted, improving extraction efficiency. The scientifically formulated composite sustained-release matrix material enables the tablets to slowly release active ingredients in the body, maintaining a stable blood drug concentration, prolonging the drug's duration of action, and reducing the frequency of dosing. The scientific formulation of natural sweeteners, flavoring agents, and fragrances effectively masks the bitter taste of Cistanche deserticola, improving patient compliance. Furthermore, the scientific formulation process and reasonable excipient formulation effectively reduce the product's hygroscopicity, improve stability, and extend shelf life. Attached Figure Description

[0016] Figure 1 This is a flowchart of the method of the present invention. Detailed Implementation

[0017] Example 1: A sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides, such as... Figure 1 As shown, it consists of the following components by weight percentage: 20% Cistanche deserticola extract, 30% sustained-release matrix material (including 15% hydroxypropyl methylcellulose, 5% sodium alginate, and 10% microcrystalline cellulose), 35% chewing filler (including 25% mannitol and 10% compressible starch), 5% natural sweetener (maltitol and isomalt in a 1:1 ratio), 2% flavoring agent (citric acid and malic acid in a 2:1 ratio), 1% flow aid (micronized silica gel), 1% lubricant (magnesium stearate), and 0.5% natural flavoring (orange flavoring).

[0018] A method for preparing a sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides, comprising the above-mentioned sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides, specifically including the following steps: Step 1: Raw material pretreatment: After washing the Cistanche deserticola raw material, cut it into 2-3cm thick slices, spray it with vitamin C solution (the amount of vitamin C sprayed is 3% of the mass of Cistanche deserticola), and then dry it with hot air at 50℃ until the moisture content is 7%; Step 2: Gradient baking: The pre-treated Cistanche deserticola slices are subjected to three-stage gradient baking. The first stage is at 105℃ and 110rpm for 5 minutes, the second stage is at 85℃ and 80rpm for 18 minutes, and the third stage is at 60℃ and 180rpm for 10 minutes. Step 3: Extract preparation: The Cistanche deserticola slices after gradient roasting were pulverized to 80 mesh and extracted using ultrasonic-assisted extraction (ethanol concentration 60%, material-liquid ratio 1:12, ultrasonic power 400W, extraction temperature 55℃, extraction time 40min, extraction twice). The extracts were combined, concentrated and dried to obtain Cistanche deserticola extract rich in phenylethanoid glycosides (the total phenylethanoid glycoside content was determined to be 38.5%, of which the total content of echinacoside and ergosterol was 22.3%). Step 4: Material mixing: Add the Cistanche deserticola extract, slow-release matrix material, chewable filler, natural sweetener, flavoring agent and natural flavoring into the three-dimensional motion mixer in proportion and mix for 30 minutes to ensure uniform mixing; Step 5: Granulation and tableting: Add 20% of 8% polyvinylpyrrolidone K30 ethanol solution to the mixture as a binder to form a soft mass, granulate it through a 20-mesh sieve, dry it at 55℃ until the moisture content is 2.5%, granulate it, add a glidant and lubricant, mix it evenly, and then compress it into tablets using a tableting machine (pressure 15kN, tablet weight 1.5g / tablet, tablet hardness 60N).

[0019] Gradient baking technology effectively preserves the phenylethanoid glycosides, especially echinacoside and ergosterol, in Cistanche deserticola, while promoting the release of polysaccharides and other components, thus improving extraction efficiency. The scientifically formulated composite sustained-release matrix material allows the tablets to slowly release active ingredients in the body, maintaining stable blood drug concentrations, prolonging the duration of drug action, and reducing the frequency of dosing. The scientific combination of natural sweeteners, flavoring agents, and fragrances effectively masks the bitter taste of Cistanche deserticola, improving patient compliance. Scientific formulation processes and reasonable excipient formulation effectively reduce the product's hygroscopicity, improve stability, and extend shelf life.

[0020] Example 2: This example describes a sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides, such as... Figure 1As shown, it consists of the following components by weight percentage: 25% Cistanche deserticola extract, 35% sustained-release matrix material (including 17% hydroxypropyl methylcellulose, 6% sodium alginate, and 12% microcrystalline cellulose), 25% chewing filler (including 18% mannitol and 7% compressible starch), 6% natural sweetener (a mixture of maltitol and isomaltitol in a 1:1.5 ratio), 2.5% flavoring agent (a mixture of citric acid and malic acid in a 2.5:1 ratio), 1.5% flow aid (micronized silica gel), 1.2% lubricant (magnesium stearate), and 0.8% natural flavoring (pineapple flavoring).

[0021] The preparation method is similar to that in Example 1, except that: in the second step, the first stage of gradient baking is rotated and baked at 108℃ for 4.5 min, the second stage is rotated and baked at 88℃ for 16 min, and the third stage is rotated and baked at 62℃ for 11 min; the extraction conditions in the third step are ethanol concentration of 65%, material-liquid ratio of 1:13, and ultrasonic power of 450W; in the fifth step, the tableting pressure is 12kN and the tablet weight is 1.2g / tablet.

[0022] Example 3: The sustained-release solid chewable tablets rich in Cistanche deserticola phenylethanoid glycosides of this example, such as... Figure 1 As shown, it consists of the following components by weight percentage: 15% Cistanche deserticola extract, 40% sustained-release matrix material (including 20% ​​hydroxypropyl methylcellulose, 8% sodium alginate, and 12% microcrystalline cellulose), 30% chewing filler (including 20% ​​mannitol and 10% compressible starch), 4% natural sweetener (maltitol and isomalt in a 1:1 ratio), 1.5% flavoring agent (citric acid and malic acid in a 2:1 ratio), 1% flow aid (micronized silica gel), 1% lubricant (magnesium stearate), and 0.5% natural flavoring (strawberry flavoring).

[0023] The preparation method is similar to that in Example 1, except that: in the second step, the first stage of gradient baking is rotated and baked at 102℃ for 5.5 min, the second stage is rotated and baked at 82℃ for 19 min, and the third stage is rotated and baked at 58℃ for 9 min; the extraction conditions in the third step are ethanol concentration of 55%, material-liquid ratio of 1:11, and ultrasonic power of 350W; in the fifth step, the tableting pressure is 18kN and the tablet weight is 1.8g / tablet.

[0024] Comparative Example 1: Compared with Example 1, the Cistanche deserticola raw material was not subjected to gradient baking treatment, but instead was dried at a constant temperature of 60°C for 2 hours using traditional methods. Other components and processes were the same as in Example 1.

[0025] Comparative Example 2: Compared with Example 1, a slow-release matrix material was not used; instead, an equal amount of ordinary filler (microcrystalline cellulose and lactose) was used. Other components and processes were the same as in Example 1.

[0026] Comparative Example 3: Compared with Example 1, no natural sweeteners or flavoring agents were added, and the other components and processes were the same as in Example 1.

[0027] Experimental Example 1: In vitro dissolution test: Tablets prepared according to Examples 1, 2, and 3, and Comparative Examples 1 and 2 were tested for dissolution using Method II (paddle method) of the 2020 edition of the Chinese Pharmacopoeia, with artificial gastric fluid (pH 1.2) as the dissolution medium, a rotation speed of 50 rpm, and a temperature of 37°C. Samples were taken at 1, 2, 4, 6, and 8 hours to determine the cumulative release rate of total phenylethyl glycosides. The results are shown in Table 1.

[0028] Table 1. Results of in vitro dissolution assay (cumulative release rate %) As can be seen from the results in Table 1, the chewable tablets prepared in Examples 1, 2 and 3 of this invention exhibit good sustained-release characteristics within 8 hours, with total phenylethyl glycosides released slowly. In contrast, Comparative Example 2 (without sustained-release matrix) released more than 95% of the drug within 4 hours, exhibiting rapid-release characteristics. The release rate of Comparative Example 1 (without gradient baking) was also significantly faster than that of Example 1, indicating that gradient baking treatment may have affected the physicochemical properties of the extract, thereby affecting the release behavior.

[0029] Experimental Example 2: Taste Evaluation: Twenty evaluators were organized to conduct a taste evaluation on the tablets prepared in Example 1, Example 2, Example 3 and Comparative Example 3. The evaluation was based on four aspects: sweetness, acidity, bitterness residue and overall acceptability. Each aspect was scored out of 5 points (a higher score indicates a better evaluation). The results were averaged and are shown in Table 2.

[0030] Table 2 Taste Evaluation Results As can be seen from the results in Table 2, the chewable tablets prepared in Examples 1, 2 and 3 performed well in terms of sweetness, acidity and masking of bitterness, and had high overall acceptability; while the scores of Comparative Example 3 (without sweeteners and flavoring agents) were very low, especially the bitterness, and the acceptability was poor.

[0031] Test Example 3: Stability Test The chewable tablets prepared in Example 1 were subjected to accelerated testing (temperature 40℃±2℃, relative humidity 75%±5%) according to the stability test guidelines of the 2020 edition of the Chinese Pharmacopoeia. Samples were taken at 0, 1, 2, 3 and 6 months to examine the changes in tablet appearance, hardness, disintegration time and total glycoside content of phenylethanol. The results are shown in Table 3.

[0032] Table 3. Results of accelerated stability test (Example 1) As can be seen from the results in Table 3, the chewable tablets prepared by this invention showed no significant changes in appearance during the 6-month accelerated test. The hardness decreased slightly but did not affect the use. The disintegration time was slightly prolonged but still met the requirements. The total glycoside content of phenylethanol remained above 90%, indicating that the product has good stability.

[0033] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides, characterized in that... It is composed of the following components by weight percentage: 15-30% Cistanche deserticola extract, 20-40% sustained-release matrix material, 15-35% chewable filler, 3-8% natural sweetener, 1-3% flavoring agent, 0.5-2% flow aid, 0.5-1.5% lubricant and 0.2-1% natural flavoring.

2. The sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides according to claim 1, characterized in that: The total phenylethyl glycoside content of the Cistanche deserticola extract is not less than 35%, of which the total content of echinacoside and ergosterol is not less than 20%.

3. The sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides according to claim 1, characterized in that: The sustained-release matrix material is a composite sustained-release system composed of hydroxypropyl methylcellulose, sodium alginate and microcrystalline cellulose in a weight ratio of 3-5:1-2:2-4.

4. The sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides according to claim 1, characterized in that: The chewable filler is a mixture of mannitol and compressible starch in a weight ratio of 2-4:1, and the natural sweetener is a mixture of maltitol and isomaltitol in a weight ratio of 1:1-2.

5. The sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides according to claim 1, characterized in that: The flavoring agent is a compound acidifier composed of citric acid and malic acid in a weight ratio of 2-3:1; the flow aid is micronized silica gel; the lubricant is magnesium stearate; and the natural flavoring is one or a combination of orange, pineapple, or strawberry flavorings.

6. A method for preparing a sustained-release solid chewable tablet rich in Cistanche deserticola phenylethanoid glycosides, characterized in that, The sustained-release solid chewable tablets rich in Cistanche deserticola phenylethanoid glycosides as described in any one of claims 1-5 specifically include the following steps: Step 1: Raw material pretreatment: After washing the Cistanche deserticola raw material, cut it into 2-3cm thick slices, spray it with vitamin C solution, and then dry it with hot air at 45-55℃ until the moisture content is ≤8%; Step 2: Gradient baking: The pre-treated Cistanche deserticola slices are baked in three stages of gradient baking. The first stage is at 100-110℃ for 4-6 minutes, the second stage is at 80-90℃ for 15-20 minutes, and the third stage is at 55-65℃ for 8-12 minutes. Step 3: Extract preparation: The Cistanche deserticola slices after gradient baking are pulverized to 50-100 mesh, extracted with ultrasonic-assisted ethanol aqueous solution, concentrated and dried to obtain Cistanche deserticola extract rich in phenylethanoid glycosides. Step 4: Material Mixing: Mix the Cistanche deserticola extract, slow-release matrix material, chewable filler, natural sweetener, flavoring agent and natural flavoring evenly in proportion; Step 5: Granulation and tableting: The mixture is granulated by wet method, dried and sized, then flow aid and lubricant are added, mixed evenly and then tableted.

7. The method for preparing sustained-release solid chewable tablets rich in Cistanche deserticola phenylethanoid glycosides according to claim 6, characterized in that: The conditions for ultrasonic-assisted extraction in the third step are: ethanol concentration 50-70%, material-to-liquid ratio 1:10-15, ultrasonic power 300-500W, extraction temperature 50-60℃, extraction time 30-45min, and extraction 2-3 times.

8. The method for preparing sustained-release solid chewable tablets rich in Cistanche deserticola phenylethanoid glycosides according to claim 6, characterized in that: In the fifth step, the binder used in wet granulation is a 5-10% polyvinylpyrrolidone K30 ethanol solution, with a dosage of 15-25% of the total weight of the material. The drying temperature is 50-60℃, and the material is dried until the moisture content is ≤3%.

9. The method for preparing sustained-release solid chewable tablets rich in Cistanche deserticola phenylethanoid glycosides according to claim 6, characterized in that: In the fifth step, the tableting pressure is 10-20kN, the tablet weight is 1.0-2.0g / tablet, and the tablet hardness is 40-80N.

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