Chuanxiong rhizome stem and leaf chewable tablet as well as preparation method and application thereof

Abstract

The embodiment of the invention discloses hemlock parsley stem and leaf chewable tablets as well as a preparation method and application thereof. The hemlock parsley stem and leaf chewable tablet is prepared from 5 to 25 parts of hemlock parsley stem and leaf freeze-dried powder, 20 to 60 parts of mannitol, 0.6 to 3.4 parts of citric acid, 1 to 25 parts of xylitol, 10 to 50 parts of maltodextrin, 0.5 to 1.7 parts of magnesium stearate and 0.1 to 0.5 part of mogroside. The Ligusticum wallichii stem and leaf freeze-dried powder is used as a main component, the optimum proportion of auxiliary materials is determined by screening the auxiliary materials such as maltodextrin, xylitol and magnesium stearate, the Ligusticum wallichii stem and leaf chewable tablet is prepared, the tablet weight difference, friability inspection, hardness and other quality inspection of the Ligusticum wallichii stem and leaf chewable tablet all accord with relevant provisions of pharmacopeia, and the Ligusticum wallichii stem and leaf chewable tablet also has antioxidant activity. The method effectively utilizes the waste biomass resource of ligusticum wallichii, makes the best use of materials and turns waste into wealth, and provides demonstration for development and utilization of the stem and leaf resource of ligusticum wallichii.

Description

Technical Field

[0001] The embodiments of the present invention relate to the technical field of pharmaceutical preparations, and in particular to a chuanxiong stem and leaf chewable tablet and a preparation method and application thereof. Background Art

[0002] Chuanxiong is the dried rhizome of the Umbelliferae plant Chuanxiong. It is warm in nature and pungent in taste. It has the effects of promoting blood circulation and qi, dispelling wind and relieving pain. Chuanxiong mainly contains volatile oils, alkaloids, polysaccharides and other biologically active ingredients. It has analgesic, anti-inflammatory, antioxidant, anti-tumor, anticoagulant and other pharmacological effects. It is used to treat cardiovascular and cerebrovascular, respiratory, nervous system and other diseases.

[0003] The stems and leaves of Chuanxiong, the above-ground parts of Chuanxiong (Miwu), account for 75% of the fresh weight of the whole plant. Most of them are directly thrown away during the harvesting and processing process, resulting in a huge waste of resources. In order to further develop and utilize Chuanxiong and tap the development potential of its non-medicinal parts, the research team conducted a preliminary study on the chemical composition and pharmacodynamics of various parts of Chuanxiong. It was found that the stems and leaves of Chuanxiong have similar chemical compositions and pharmacological effects as the traditional medicinal parts of Chuanxiong, the rhizomes, which preliminarily revealed the huge research space of the traditional "non-medicinal parts" of Chuanxiong. The stems and leaves of Chuanxiong are rich in various nutrients such as vitamins, dietary fiber, iron and zinc, and are a food with great nutritional value. In addition, the stems and leaves of Chuanxiong are widely used in salads, fried foods and cooking in other parts of Asia, such as Japan and South Korea, to relieve dizziness. Studies have shown that the maximum tolerated dose determination method in mice has proved that the stems and leaves of Chuanxiong are not toxic and are very safe overall. Summary of the invention

[0004] To this end, the embodiment of the present invention provides a Chuanxiong stem and leaf chewable tablet and a preparation method and application thereof. The present invention uses Chuanxiong stem and leaf freeze-dried powder (Miwu freeze-dried powder) as the main component, screens auxiliary materials such as maltodextrin, xylitol, and magnesium stearate, determines the optimal ratio of auxiliary materials, prepares a Chuanxiong stem and leaf chewable tablet, and further performs quality inspection and antioxidant function evaluation on it. The present invention effectively utilizes Chuanxiong waste biomass resources, "makes the best use of everything and turns waste into treasure", and provides a demonstration for the development and utilization of Chuanxiong stem and leaf resources.

[0005] In order to achieve the above purpose, the embodiment of the present invention provides the following technical solutions:

[0006] According to a first aspect of an embodiment of the present invention, the present invention provides a Chuanxiong stem and leaf chewable tablet, which comprises, by weight, 5-25 parts of Chuanxiong stem and leaf freeze-dried powder, 20-60 parts of mannitol, 0.6-3.4 parts of citric acid, 1-25 parts of xylitol, 10-50 parts of maltodextrin, 0.5-1.7 parts of magnesium stearate, and 0.1-0.5 parts of mogroside.

[0007] Furthermore, the Chuanxiong stem and leaf chewable tablets include 9.4 parts of Chuanxiong stem and leaf freeze-dried powder, 40 parts of mannitol, 2 parts of citric acid, 7 parts of xylitol, 41 parts of maltodextrin, 1.4 parts of magnesium stearate, and 0.4 parts of mogroside.

[0008] Furthermore, the preparation method of the freeze-dried powder of Chuanxiong stems and leaves is as follows:

[0009] Fresh chuanxiong stems and leaves in a mass-to-volume ratio of 240 g:350 ml are mixed with distilled water and beaten into a pulp. Based on the mass of the fresh chuanxiong stems and leaves, 7% maltodextrin and 7% xylitol are added, and the mixture is stirred evenly. The mixture is pre-frozen at -60°C for 5 hours, and then vacuum-freeze-dried at a vacuum degree of ≤10 Pa for 28 hours, and crushed to obtain the chuanxiong stem and leaf freeze-dried powder.

[0010] According to a second aspect of an embodiment of the present invention, the present invention provides a method for preparing the above-mentioned Chuanxiong stem and leaf chewable tablets, the method comprising the following steps:

[0011] (1) Mixing raw materials and auxiliary materials: Mix the freeze-dried powder of Chuanxiong stems and leaves, mannitol, citric acid, xylitol, maltodextrin, and mogroside uniformly, and pass through a 50-mesh sieve;

[0012] (2) Preparation of soft materials: Use 95% ethanol for spraying and granulation, and the amount used should be controlled to the state of "forming a ball when held and falling apart when lightly pressed";

[0013] (3) Granulation: Granulation was performed using a swing granulator;

[0014] (4) Drying: Place in a dryer at a temperature of 60-70° C. until the moisture content of the granules is 1.8-2.2%;

[0015] (5) Granulation: sieve the granules through a 20-mesh sieve, and then sieve the granules through a 50-mesh sieve and add magnesium stearate;

[0016] (6) Tablet pressing: Place in a tablet press for compression.

[0017] Furthermore, in step (3), the parameters of the swing granulator are set as: screen size 40 mesh, drum speed 40-50 r / min.

[0018] Furthermore, in step (4), the temperature of the drying machine is 65° C. and the drying time is 60 minutes.

[0019] Furthermore, in step (6), the pressing conditions are: circular 10# die, feeding speed 35r / min, main pressure 2N.

[0020] According to a third aspect of an embodiment of the present invention, the present invention provides use of the above-mentioned Chuanxiong stem and leaf chewable tablets in the preparation of an antioxidant active product.

[0021] The embodiments of the present invention have the following advantages:

[0022] The present invention obtains the optimal formulation process of Chuanxiong stem and leaf chewable tablets through single factor investigation and response surface optimization. The tablet weight difference, hardness test and friability test in the quality inspection all meet the requirements. The protein content of Chuanxiong stem and leaf chewable tablets was experimentally determined to be 3.23g / 100g, the crude fat content was 0.32g / 100g, the moisture content was 2.52g / 100g, the ash content was 0.84g / 100g, and the total carbohydrate content was 93.09g / 100g. The results of the determination of the DPPH scavenging ability of Chuanxiong stem and leaf chewable tablets were used to calculate the half inhibition concentration (IC 50 ) was 97.75±0.99 mg / mL; the results of the determination of ABTS+· scavenging ability were used to calculate the IC 50 It is 10.39±2.15mg / mL.

[0023] The invention uses the stems and leaves of Chuanxiong as raw materials to prepare a chewable tablet with antioxidant activity, which can effectively utilize the discarded biomass resources of Chuanxiong, "make the best use of things and turn waste into treasure", and provide a demonstration for the circular economic utilization of traditional Chinese medicine resources. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the implementation methods of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for the implementation methods or the description of the prior art. Obviously, the drawings in the following description are only exemplary, and for ordinary technicians in this field, other implementation drawings can be derived from the provided drawings without creative work.

[0025] Figure 1 A preparation flow chart of the Chuanxiong stem and leaf chewable tablets provided by the present invention;

[0026] Figure 2 The total amount of each freeze-dried powder of Chuanxiong stems and leaves provided by the present invention;

[0027] Figure 3 The total score of each dosage of mannitol provided by the present invention;

[0028] Figure 4 The total score of each amount of citric acid provided by the present invention;

[0029] Figure 5 The total amount of xylitol provided by the present invention;

[0030] Figure 6 The total amount of maltodextrin provided by the present invention;

[0031] Figure 7 The total amount of magnesium stearate provided by the present invention;

[0032] Figure 8 The total score of each amount of mogroside provided by the present invention;

[0033] Fig. 9 A response surface diagram of the interaction between the freeze-dried powder of stems and leaves of Ligusticum chuanxiong and mogroside provided by the present invention;

[0034] Fig.10 A response surface diagram of the interaction between the freeze-dried powder of Rhizoma Chuanxiong stems and leaves and maltodextrin provided by the present invention;

[0035] Fig.11 A response surface diagram of the interaction between mogroside and maltodextrin provided by the present invention;

[0036] Fig.12 This is a photo of the appearance of the Chuanxiong stem and leaf chewable tablet provided by the present invention;

[0037] Fig.13 The DPPH scavenging ability of the Chuanxiong stem and leaf chewable tablet powder provided by the present invention;

[0038] Fig.14 The chuanxiong stem and leaf chewable tablet powder provided by the present invention removes ABTS + ·ability. DETAILED DESCRIPTION

[0039] The following is a description of the implementation of the present invention by specific embodiments. People familiar with the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. 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.

[0040] Example 1

[0041] 1. Instruments and test drugs

[0042] 1.1 Reagents and Materials

[0043] Table 1 Reagents and materials

[0044]

[0045]

[0046] Wherein, the preparation method of chuanxiong stem and leaf freeze-dried powder is as follows:

[0047] Add 240g of fresh Ligusticum chuanxiong stems and leaves into 350ml of distilled water to prepare a slurry (100r / min, 3min), add freeze-drying protective agent (7% maltodextrin and 7% xylitol based on the weight of fresh Ligusticum chuanxiong stems and leaves), stir evenly (100r / min, 2min), perform pre-freezing treatment at -60℃ for 5h, and then perform vacuum freeze-drying. The conditions for vacuum freeze-drying are: vacuum degree ≤10Pa, time 28h, and after completion, use a grinder to grind to obtain Ligusticum chuanxiong stem and leaf freeze-dried powder.

[0048] 1.2 Instruments

[0049] Table 2 Instruments

[0050]

[0051] 2. Experimental Methods

[0052] 2.1 Preparation process of Chuanxiong stem and leaf chewable tablets

[0053] See also Figure 1 The preparation process of Chuanxiong stem and leaf chewable tablets includes:

[0054] Mixing of raw and auxiliary materials: add freeze-dried powder of Chuanxiong stems and leaves, xylitol, maltodextrin, citric acid, mannitol and mogroside raw and auxiliary materials (except magnesium stearate) in sequence according to proportion, mix well and pass through a 50-mesh sieve.

[0055] Making soft materials: Use 95% ethanol for spraying and granulation, and the amount used should be controlled to the state of "forming a ball when held and falling apart when pressed lightly".

[0056] Granulation: Granulation was performed using a swing granulator, the parameters of which were set as follows: screen size 40 mesh, drum speed 46 r / min.

[0057] Drying and granulation: temperature 65°C, time 60min, drying until the moisture content of the granules is about 2%. Granulate through a 20-mesh sieve, and add magnesium stearate as a lubricant after passing through a 50-mesh sieve.

[0058] Tablet pressing: Stir the materials evenly and put them into the tablet press for pressing. The pressing conditions are: round 10# punch die, feeding speed 35r / min, main pressure 2N.

[0059] 2.2 Basic prescription

[0060] Table 3 Prescription design of Chuanxiong stem and leaf chewable tablets

[0061]

[0062] 2.3 Study on the formulation and process of Chuanxiong stem and leaf chewable tablets

[0063] 2.3.1 Single Factor Study

[0064] (1) Screening of the dosage of freeze-dried powder of stems and leaves of Chuanxiong: Under the conditions of 25 parts of xylitol, 20 parts of maltodextrin, 20 parts of mannitol, 2.4 parts of citric acid, 0.8 parts of magnesium stearate, and 0.2 parts of mogroside, the effects of adding 5 parts, 10 parts, 15 parts, 20 parts, and 25 parts of freeze-dried powder of stems and leaves of Chuanxiong on the sensory quality, angle of repose, and hardness of the chewable tablets were investigated.

[0065] (2) Screening of mannitol dosage: 10 parts of freeze-dried powder of Chuanxiong stems and leaves, 25 parts of xylitol, 20 parts of maltodextrin, 2.4 parts of citric acid, 0.8 parts of magnesium stearate, and 0.2 parts of mogroside were added to investigate the effects of adding 20 parts, 30 parts, 40 parts, 50 parts, and 60 parts of mannitol on the sensory quality, angle of repose, and hardness of the chewable tablets.

[0066] (3) Screening of citric acid dosage: Under the conditions of 10 parts of freeze-dried powder of Chuanxiong stems and leaves, 25 parts of xylitol, 20 parts of maltodextrin, 20 parts of mannitol, 0.8 parts of magnesium stearate, and 0.2 parts of mogroside, the effects of adding 0.6 parts, 1.3 parts, 2.0 parts, 2.7 parts, and 3.4 parts of citric acid on the sensory quality, angle of repose, and hardness of the chewable tablets were investigated.

[0067] (4) Screening of xylitol dosage: Under the conditions of 10 parts of freeze-dried powder of Chuanxiong stems and leaves, 20 parts of maltodextrin, 20 parts of mannitol, 2.4 parts of citric acid, 0.8 parts of stearic acid, and 0.2 parts of mogroside, the effects of adding 1 part, 7 parts, 13 parts, 19 parts, and 25 parts of xylitol on the sensory quality, angle of repose, and hardness of the chewable tablets were investigated.

[0068] (5) Screening of maltodextrin dosage: Under the conditions of 10 parts of freeze-dried powder of Chuanxiong stems and leaves, 25 parts of xylitol, 20 parts of mannitol, 2.4 parts of citric acid, 0.8 parts of magnesium stearate, and 0.2 parts of mogroside, the effects of adding 10 parts, 20 parts, 30 parts, 40 parts, and 50 parts of maltodextrin on the sensory quality, angle of repose, and hardness of the chewable tablets were investigated.

[0069] (6) Screening of magnesium stearate dosage: Under the conditions of 10 parts of freeze-dried powder of Chuanxiong stems and leaves, 25 parts of xylitol, 20 parts of maltodextrin, 20 parts of mannitol, 2.4 parts of citric acid, and 0.2 parts of mogroside, the effects of adding 0.5 parts, 0.8 parts, 1.1 parts, 1.4 parts, and 1.7 parts of magnesium stearate on the sensory quality, angle of repose, and hardness of the chewable tablets were investigated.

[0070] (7) Screening of the dosage of mogroside: Under the conditions of 10 parts of freeze-dried powder of Chuanxiong stems and leaves, 25 parts of xylitol, 20 parts of maltodextrin, 20 parts of mannitol, 2.4 parts of citric acid, and 0.8 parts of magnesium stearate, the effects of adding 0.1 part, 0.2 part, 0.3 part, 0.4 part, and 0.5 part of mogroside on the sensory quality, angle of repose, and hardness of the chewable tablets were investigated.

[0071] 2.3.2 Process Optimization

[0072] According to the results of the single-factor experiment, the three factors that had the greatest impact on the chewable tablets were selected as experimental factors. The response surface Box-Behnken experimental design was used to conduct a three-factor three-level experimental design with sensory scores as the response value.

[0073] 2.3.3 Scoring criteria and calculation

[0074] According to the purpose of the experiment, the appearance, taste, angle of repose and hardness of chewable tablets were used as evaluation indicators, and the weight of each of the four was 0.25. The comprehensive weighted scoring method was used to evaluate the influence of the main factors in the prescription on the quality of chewable tablets. The scores of each factor in the single factor investigation were calculated according to formula (1), and the experimental group with the highest total score was selected as the prescription dosage. The calculation formula is as follows:

[0075] X=0.25A+0.25B+0.25C+0.25D (1)

[0076] X: total score; A: appearance score; B: taste score; C: angle of repose score; D: hardness score.

[0077] (1) Sensory evaluation

[0078] Sensory evaluation: The appearance and taste of chewable tablets were the main evaluation points. 10 sensory examiners were selected to introduce the method and scoring table, conduct consensus training on the sample set, and then score different samples according to Table 4.

[0079] Table 4 Sensory rating table

[0080]

[0081] (2) Method for measuring the angle of repose

[0082] Material fluidity measurement: In the process of preparing chewable tablets, the fluidity of the material is one of the important factors. The angle of repose refers to the maximum angle formed by the free slope of the powder pile and the horizontal plane. The angle of repose is measured using a powder physical property tester, and the results are scored according to Table 5.

[0083] Table 5 Repose angle scoring table

[0084]

[0085] (3) Hardness measurement method

[0086] Hardness test: Use a tablet hardness tester to test the hardness of 6 tablets of this product, and take the average value of the results. Score according to Table 6.

[0087] Table 6 Hardness rating table

[0088]

[0089] 2.4 Quality Inspection of Chuanxiong Stem and Leaf Chewable Tablets

[0090] 2.4.1 Appearance

[0091] Check the appearance of the Chuanxiong stem and leaf chewable tablets, which should be complete and smooth, with uniform color, no spots, and no foreign matter.

[0092] 2.4.2 Tablet weight differences

[0093] The weight difference is checked in accordance with General Rules 0101 of Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China. The difference limits are shown in Table 7.

[0094] Table 7 Weight Difference Limits of Chinese Pharmacopoeia

[0095]

[0096] 2.4.3 Hardness

[0097] Randomly sample 6 tablets and place them in a tablet hardness tester to test the hardness. The hardness range of chewable tablets is 50-70N, and no more than 2 tablets shall exceed the range.

[0098] 2.4.4 Friability

[0099] Tablet friability test was carried out in accordance with General Rule 0923 of Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China.

[0100] 2.5 Determination of nutritional components of Chuanxiong stem and leaf chewable tablets

[0101] 2.5.1 Protein determination

[0102] Determined according to GB 5009.5-2016 Kjeldahl method.

[0103] 2.5.2 Crude fat determination

[0104] Determined according to the Soxhlet extraction method of GB 5009.6-2016.

[0105] 2.5.3 Moisture determination

[0106] Determined according to the first method of GB 5009.3-2016.

[0107] 2.5.4 Ash content determination

[0108] Determined according to the first method of GB 5009.4-2016.

[0109] 2.5.5 Total carbohydrate determination

[0110] Total carbohydrates (%) = 100% - moisture (%) - fat (%) - protein (%) - ash (%)

[0111] 2.6 Antioxidant activity

[0112] (1) Preparation of DPPH solution: Weigh 0.004 g of DPPH powder accurately, add 100 mL of anhydrous ethanol to dissolve it into a solution with a concentration of 0.1 mg / mL. Dilute it with anhydrous ethanol during the experiment to make its absorbance (λ=517 nm) at 0.7±0.1. Store at 4°C for future use.

[0113] (2)ABTS + Solution preparation: Accurately weigh ABTS + · 0.384g of powder and 0.066g of potassium persulfate powder were dissolved in 100mL of anhydrous ethanol to prepare solutions with concentrations of 7.0mg / mL and 2.45mg / mL respectively. Mix the two in equal volumes and react in the dark for 16-24h to obtain ABTS + ·Mother solution. Dilute with anhydrous ethanol to make its absorbance 0.7±0.1. Store at 4℃ for future use.

[0114] (3) Preparation of sample solution: Take 1.0 g of sample powder, weigh accurately, put it in a 50 mL centrifuge tube, add 25 mL of anhydrous ethanol, shake well, extract by ultrasonic at room temperature for 30 min, centrifuge at 12000 rpm for 10 min, and take the supernatant. Dilute the supernatant to different multiples to obtain sample solutions of different concentrations.

[0115] (4) Determination of DPPH· free radical scavenging rate: Add 250 μL of DPPH· solution to each well of a 96-well plate, and add 50 μL of sample solution of different concentrations to each well. After reacting at room temperature in the dark for 30 minutes, use an enzyme reader to measure the absorbance at 517 nm and scan the UV-Vis spectrum. Use anhydrous ethanol instead of the sample solution as the negative control, and use anhydrous ethanol instead of the DPPH· solution as the sample background. Use vitamin C instead of the sample solution as the positive control. Each sample was measured three times in parallel and the average value was taken. Calculate the DPPH· scavenging rate (%) = [1-(Ae-As) / Ac]×100%. Where Ae is the absorbance of the reaction solution, Ac is the absorbance of the negative control, and As is the absorbance of the sample background. Draw a scavenging rate curve with concentration (mg / mL) as the horizontal axis and scavenging rate (%) as the vertical axis. The scavenging activity is expressed as IC 50 Indicates that IC is calculated using SPSS24 50 .

[0116] (5)ABTS + Free radical scavenging rate assay: add 250 μL ABTS to each well of a 96-well plate. +· solution, add 50μL of samples of different concentrations to each well. After 6 minutes of reaction, measure the absorbance of the reaction system at 734nm and scan the UV-Vis spectrum. Vitamin C is used as a positive control. The negative control and sample background settings are consistent with the DPPH· free radical scavenging activity determination. Each sample is measured three times in parallel and the average value is taken. Calculate ABTS + · Clearance rate (%) = [1-(Ae-As) / Ac] × 100%. In the formula, Ae is the absorbance of the reaction solution, Ac is the absorbance of the negative control, and As is the absorbance of the sample background. The clearance rate curve is drawn with concentration (mg / mL) as the horizontal axis and clearance rate (%) as the vertical axis. IC was calculated using SPSS24 50 .

[0117] 3. Experimental results and discussion

[0118] 3.1 Study on the formulation and process of Chuanxiong stem and leaf chewable tablets

[0119] 3.1.1 Single factor investigation results

[0120] (1) Screening results of dosage of freeze-dried powder of Chuanxiong stems and leaves

[0121] As can be seen from Table 8, the hardness of the stems and leaves of Chuanxiong fluctuates greatly with the different dosages. Too much hardness is not convenient for chewing. The scoring results of the freeze-dried powder of Chuanxiong stems and leaves are shown in Table 9. Figure 2 It can be seen that when the dosage of Chuanxiong stem and leaf freeze-dried powder is 10 portions, the comprehensive score reaches the highest value of 7.29, so 10 portions of Chuanxiong stem and leaf freeze-dried powder are finally selected as the prescription dosage.

[0122] Table 8 Hardness and angle of repose of Chuanxiong stem and leaf chewable tablets

[0123]

[0124] Table 9 Rating of freeze-dried powder of stems and leaves of Chuanxiong

[0125]

[0126] (2) Mannitol dosage screening results

[0127] As shown in Table 10, with the increase of mannitol dosage, the hardness of Chuanxiong stem and leaf chewable tablets gradually decreased, and the angle of repose gradually increased. Figure 3 From the data results, we can see that the total score reaches a peak of 6.78 at 40 portions, so the best dosage of mannitol is 40 portions.

[0128] Table 10 Angle of repose and hardness of mannitol

[0129]

[0130] Table 11 Mannitol score

[0131]

[0132] (3) Screening results of citric acid dosage

[0133] As can be seen from Table 12, as the amount of citric acid increases, the hardness of the Chuanxiong stem and leaf chewable tablets first gradually increases and then decreases. The citric acid scoring results are shown in Table 13. Figure 4 It can be seen that the score increases with the increase of citric acid dosage, reaching a peak of 6.77 at 2 parts, and then the score decreases with the increase of citric acid dosage, so the optimal citric acid dosage is 2 parts.

[0134] Table 12 Angle of repose and hardness of citric acid

[0135]

[0136] Table 13 Citric acid scores

[0137]

[0138] (4) Xylitol dosage screening results

[0139] As can be seen from Table 14, with the increase of xylitol content, the angle of repose and hardness generally show a trend of first increasing and then decreasing. Figure 5 It can be seen that the total score reaches a peak of 6.27 at 7 parts, so 7 parts of xylitol are selected as the prescription dosage.

[0140] Table 14 Angle of repose and hardness of xylitol

[0141]

[0142] Table 15 Xylitol Scoring

[0143]

[0144] (5) Screening results of maltodextrin dosage

[0145] As the amount of maltodextrin increases, the angle of repose increases first and then decreases, reaching a peak at 40 parts, and the taste score also shows this trend. Figure 6 It can be seen that the total score has two peaks at 20 parts and 40 parts, which are 6.60 and 6.69 respectively. The maltodextrin with a higher total score of 40 parts is selected as the prescription dosage.

[0146] Table 16 Angle of repose and hardness of maltodextrin

[0147]

[0148] Table 17 Maltodextrin Scoring

[0149]

[0150]

[0151] (6) Screening results of magnesium stearate dosage

[0152] from Figure 7 It can be seen that the total score of magnesium stearate shows an upward trend between 0.5 parts and 1.4 parts, reaching a peak of 6.18 at 1.4 parts, and then the score gradually decreases. Therefore, it can be seen that the optimal prescription dosage of magnesium stearate is 1.4 parts.

[0153] Table 18 Repose angle and hardness of magnesium stearate

[0154]

[0155] Table 19 Magnesium stearate score

[0156]

[0157] (7) Screening results of mogroside dosage

[0158] It can be seen from Table 20 that with the increase in the amount of mogroside, the angle of repose first increases and then decreases, while the change in hardness is irregular and fluctuates greatly. The results of mogroside scoring are shown in Table 21. Figure 8 It can be seen that there are two peaks of mogroside at 0.2 and 0.4 parts, which are 6.85 and 7.31 respectively. Therefore, 0.4 parts of mogroside are selected as the prescription dosage.

[0159] Table 20 Angle of repose and hardness of mogroside

[0160]

[0161]

[0162] Table 21 Mogroside Scores

[0163]

[0164] 3.2 Process optimization: response surface design results and data variance analysis of Chuanxiong stem and leaf chewable tablets

[0165] (1) Establishment of regression equation and variance analysis

[0166] According to the single factor experiment, the three factors with the greatest influence, namely, lyophilized powder of Chuanxiong stems and leaves, mogroside, and maltodextrin, were optimized. The results of the response surface test are shown in Table 22. The data were fitted with binary multiple regression, and the quadratic multiple regression model equation of the sensory score for the addition amount of lyophilized powder of Chuanxiong stems and leaves (A), the addition amount of mogroside (B), and the addition amount of maltodextrin (C) was obtained as follows:

[0167] Y=81.46-3.46A+0.41B+1.21C+1.11AB+1.97AC-0.093BC-14.01A 2 -2.48B 2 -5.

[0168] 21C 2 (2)

[0169] From the variance analysis results of the response surface quadratic regression equation (Table 23), it can be seen that the entire regression model has reached a very significant level (P<0.01), and the lack of fit term is not obvious (P>0.05), which shows that the model is correct and the regression equation can be used to predict and analyze the formula. The correlation coefficient of this formula is R 2 is 0.9828, and the discriminant factor R 2 adj The coefficient of variation (CV) is 2.39%, indicating that the experiment has certain reliability and validity. The fitting index of this model equation has a good correlation with the formula ratio.

[0170] From Table 23, we can see that A and the quadratic term A 2 , B 2 , C 2 The effect on the sensory score of Chuanxiong stem and leaf chewable tablets was significant (P < 0.01), and the other items were not significant (P > 0.05). From the F value, it can be seen that the influence of each factor on the comprehensive score is as follows: A > C > B, that is, the amount of Chuanxiong stem and leaf freeze-dried powder added > the amount of maltodextrin added > the amount of mogroside added.

[0171] The response surface graph was drawn based on the response surface regression equation, and the interaction of each factor was shown in Fig. 9 , 10 , 11. By Fig. 9 It can be seen that the amount of freeze-dried powder of Chuanxiong stems and leaves added changes more steeply, while the amount of mogroside added changes more slowly, indicating that the amount of freeze-dried powder of Chuanxiong stems and leaves added has a greater impact on the sensory evaluation of Chuanxiong stem and leaf chewable tablets than the amount of mogroside added. Fig.10It can be seen that the curve of the addition amount of Chuanxiong stem and leaf freeze-dried powder is steeper than that of maltodextrin, indicating that in the sensory evaluation of Chuanxiong stem and leaf chewable tablets, the addition amount of Chuanxiong stem and leaf freeze-dried powder has a greater impact than the addition amount of maltodextrin. Fig.11 It can be seen that the curves of the added amount of mogroside and maltodextrin are both relatively gentle, but the curve of the added amount of mogroside is steeper in comparison, indicating that the added amount of mogroside has a greater impact on the sensory evaluation of Chuanxiong stem and leaf chewable tablets than the added amount of maltodextrin.

[0172] Table 22 Response surface test results

[0173]

[0174] Table 23 Significance test and variance analysis of regression model

[0175]

[0176]

[0177] Note: * indicates significant difference, p<0.05; ** indicates extremely significant effect, p<0.01

[0178] (2) Verification test results

[0179] The Design-Expert method was used to optimize the optimal preparation process parameters: 9.43 parts of lyophilized powder of stems and leaves of Chuanxiong, 0.41 parts of mogroside, and 40.95 parts of maltodextrin. Under this condition, the sensory score was predicted to be 81.73 points. Considering the practical operation, the optimal parameters were modified to: 9.4 parts of lyophilized powder of stems and leaves of Chuanxiong, 0.4 parts of mogroside, 41 parts of maltodextrin, 40 parts of mannitol, 7 parts of xylitol, 2 parts of citric acid, and 1.4 parts of magnesium stearate.

[0180] The formula was used for three repeated verification tests, and the actual sensory score was 79 points. Compared with the predicted value, it can be seen that the optimal condition parameters obtained by experimental optimization are accurate and reliable, and have certain reference value.

[0181] 3.3 Quality Inspection of Chuanxiong Stem and Leaf Chewable Tablets

[0182] 3.3.1 Appearance properties results

[0183] According to the above optimal parameters (9.4 parts of lyophilized powder of stems and leaves of Chuanxiong, 0.4 parts of mogroside, 41 parts of maltodextrin, 40 parts of mannitol, 7 parts of xylitol, 2 parts of citric acid, and 1.4 parts of magnesium stearate), the chewable tablets of stems and leaves of Chuanxiong were prepared. Fig.12 The color is uniform yellow-brown, the surface is smooth, the edges are neat, there are no spots, and there are no foreign objects.

[0184] 3.3.2 Tablet weight difference results

[0185] The average weight of the 20 tablets was 0.46g, which is greater than 0.30g. According to the pharmacopoeia, the weight difference limit is ±5% of the average tablet weight, i.e. 0.44g to 0.48g. The weights of the 20 tablets were measured respectively. After inspection, the weights of the 20 tablets were within the weight difference limit, and the tablet weight difference was qualified.

[0186] Table 24 Tablet weight differences

[0187]

[0188] 3.3.3 Hardness test results

[0189] The 2020 edition of the "Pharmacopoeia of the People's Republic of China" states: "The hardness of chewable tablets should be appropriate", but does not give a specific hardness range. However, by searching domestic and foreign literature and referring to the US FDA's guidelines for chewable tablet quality evaluation, it is concluded that the hardness of chewable tablets is in a relatively reasonable range of 50N-118N.

[0190] In this study, 6 pills were randomly selected for hardness measurement. The hardnesses were 63.42, 57.27, 55.99, 60.30, 59.66, and 62.93 N, respectively. The average hardness was 59.93 N. The hardness of each pill was within a reasonable range.

[0191] Table 25 Hardness determination

[0192]

[0193] 3.3.4 Friability test results

[0194] The initial weight of the 14 tablets was 6.4342 g, and the weight at the end of the friability test was 6.4182 g. The weight loss before and after the test was 0.016 g, which was less than 1% of the initial weight (0.0643 g), which was in compliance with the pharmacopoeia requirements.

[0195] Table 26 Friability results

[0196]

[0197] 3.4 Determination of nutritional components of Chuanxiong stem and leaf chewable tablets

[0198] The experimental determination of protein content, crude fat content, moisture content, and ash content was carried out under repeatability conditions and two independent determination results were obtained. After the calculation and verification precision met the requirements, the two results were averaged. As shown in Table 27, the protein content of Chuanxiong stem and leaf chewable tablets was 3.23g / 100g, the crude fat content was 0.32g / 100g, the moisture content was 2.52g / 100g, the ash content was 0.84g / 100g, and the total carbohydrate content was 93.09g / 100g.

[0199] Table 27 Nutritional composition of Chuanxiong stem and leaf chewable tablets

[0200]

[0201] 3.5 Antioxidant activity results

[0202] 3.5.1 Results of the DPPH scavenging ability test of Chuanxiong stem and leaf chewable tablets

[0203] The average values ​​of tablet powder clearance rate and vitamin C clearance rate obtained from three parallel experiments are shown in Table 28. The scavenging ability of Chuanxiong stem and leaf chewable tablets on DPPH free radicals is shown in Fig.13 The scavenging ability of Chuanxiong stem and leaf chewable tablets on DPPH· free radicals is positively correlated with its concentration, that is, it increases with the increase of concentration. When the concentration reaches 40 mg / mL, the scavenging rate of the tablet powder on DPPH· reaches a maximum of 33.20%. The IC 50 It is 97.75±0.99mg / mL.

[0204] Table 28 DPPH experimental data

[0205]

[0206] 3.5.2 Ligusticum chuanxiong stem and leaf chewable tablets to remove ABTS + · Results of ability measurement

[0207] The average values ​​of the tablet powder clearance rate and vitamin C clearance rate obtained from three parallel experiments are shown in Table 29. + · Free radical scavenging ability Fig.14 Effect of Chuanxiong Stem and Leaf Chewable Tablets on ABTS + The free radical scavenging ability is positively correlated with its concentration, that is, it increases with the increase of concentration. When the concentration reaches 40 mg / mL, the tablet powder has a + The clearance rate of · reached a maximum of 78.57%. The IC 50 It is 10.39±2.15mg / mL.

[0208] Table 29 ABTS + Experimental data

[0209]

[0210] The present invention prepares a chewable tablet with chuanxiong stem and leaf as a main drug and maltodextrin, xylitol, citric acid and the like as auxiliary materials. The experiment carried out protein determination, crude fat determination, moisture determination and ash determination on the chuanxiong stem and leaf chewable tablet. According to the relevant provisions of the pharmacopoeia, the tablet weight difference, friability inspection, hardness determination and other quality inspections were carried out, and all of them met the requirements. The antioxidant activity experiment proved that the chuanxiong stem and leaf chewable tablet had antioxidant activity.

[0211] Although the present invention has been described in detail above by general description and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements can be made to the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all belong to the scope of protection claimed by the present invention.

Claims

1. A chewable tablet of chuanxiong stem and leaf, characterized in that: By weight, the Chuanxiong stem and leaf chewable tablets include 5-25 parts of Chuanxiong stem and leaf freeze-dried powder, 20-60 parts of mannitol, 0.6-3.4 parts of citric acid, 1-25 parts of xylitol, 10-50 parts of maltodextrin, 0.5-1.7 parts of magnesium stearate, and 0.1-0.5 parts of mogroside.

2. The Chuanxiong stem and leaf chewable tablet according to claim 1, characterized in that: The Chuanxiong stem and leaf chewable tablet comprises 9.4 parts of Chuanxiong stem and leaf freeze-dried powder, 40 parts of mannitol, 2 parts of citric acid, 7 parts of xylitol, 41 parts of maltodextrin, 1.4 parts of magnesium stearate and 0.4 parts of mogroside.

3. The Chuanxiong stem and leaf chewable tablet according to claim 1, characterized in that: The preparation method of the lyophilized powder of Rhizoma Chuanxiong stems and leaves is as follows: Fresh chuanxiong stems and leaves in a mass-to-volume ratio of 240 g:350 ml are mixed with distilled water and beaten into a pulp. Based on the mass of the fresh chuanxiong stems and leaves, 7% maltodextrin and 7% xylitol are added, and the mixture is stirred evenly. The mixture is pre-frozen at -60°C for 5 hours, and then vacuum-freeze-dried at a vacuum degree of ≤10 Pa for 28 hours, and crushed to obtain the chuanxiong stem and leaf freeze-dried powder.

4. The method for preparing the Chuanxiong stem and leaf chewable tablets according to any one of claims 1 to 3, characterized in that: The method comprises the following steps: (1) Mixing raw materials and auxiliary materials: Mix the freeze-dried powder of Chuanxiong stems and leaves, mannitol, citric acid, xylitol, maltodextrin, and mogroside uniformly, and pass through a 50-mesh sieve; (2) Preparation of soft materials: Use 95% ethanol for spraying and granulation, and the amount used should be controlled to the state of "forming a ball when held and falling apart when lightly pressed"; (3) Granulation: Granulation was performed using a swing granulator; (4) Drying: Place in a dryer at a temperature of 60-70° C. until the moisture content of the granules is 1.8-2.2%; (5) Granulation: sieve the granules through a 20-mesh sieve, and then sieve the granules through a 50-mesh sieve and add magnesium stearate; (6) Tablet pressing: Place in a tablet press for compression.

5. The method for preparing the Chuanxiong stem and leaf chewable tablets according to claim 4, characterized in that: In step (3), the parameters of the swing granulator are set as follows: screen 40 mesh, drum speed 40-50 r / min.

6. The method for preparing the Chuanxiong stem and leaf chewable tablets according to claim 4, characterized in that: In step (4), the temperature of the drying machine is 65° C. and the time is 60 min.

7. The method for preparing the Chuanxiong stem and leaf chewable tablets according to claim 4, characterized in that: In step (6), the pressing conditions are: circular 10# punch die, feeding speed 35r / min, main pressure 2N.

8. Use of the Chuanxiong stem and leaf chewable tablets according to claim 1 in the preparation of products with antioxidant activity.

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