Five-flavor sweet medicine bath infusion paste effervescent tablet and preparation method

Abstract

The application discloses a kind of five-flavor Ganlu medicated bath extract effervescent tablets and preparation method, by mass percentage, the effervescent tablet includes five-flavor Ganlu medicated bath extract powder 20%, effervescent agent 55% consisting of citric acid and sodium bicarbonate, 2% crosslinked sodium carboxymethyl cellulose, 2% magnesium stearate and auxiliary material 21% consisting of microcrystalline cellulose, pre-gelatinized starch and sodium carboxymethyl starch.The five-flavor Ganlu medicated bath extract powder is prepared from juniper, rhododendron anthoropogon, water berberis, artemisia japonica, ephedra, prunus divaricata, polygonatum, tribulus terrestris, satyrium, gancao, terminalia chebula, emblica, terminalia and himalayan mallow by water extraction, concentration, reduced pressure drying, crushing and sieving, and the effervescent tablet is prepared by dry granulation and tabletting.The effervescent tablet obtained by the application has fast effervescent disintegration, good dispersibility and formability, and is convenient to use, store and carry.

Description

Technical Field

[0001] This invention belongs to the field of Tibetan medicine preparation technology, specifically relating to a five-flavor sweet dew medicinal bath extract effervescent tablet and its preparation method. Background Technology

[0002] The Five-Flavor Sweet Dew Medicated Bath series of preparations originates from classic Tibetan medicine prescriptions and has the effects of clearing heat and reducing swelling, relaxing muscles and tendons, and promoting blood circulation. Clinically, it is used for medicated bath treatment of diseases such as rheumatoid arthritis. Traditional medicated bath powders usually need to be decocted or soaked for a long time before use, which has problems such as many operation steps, slow dispersion, and inconvenience in storage and carrying.

[0003] To improve the ease of use and stability of traditional Five-Flavor Sweet Dew Bath preparations, it is necessary to optimize the extraction, drying, and molding processes while retaining the prescription medicinal materials, clarify key process parameters, and develop a new dosage form that effervescently disintegrates quickly, has controllable quality, and is easy to store and carry. Summary of the Invention

[0004] The purpose of this invention is to provide a Five-Flavor Sweet Dew Bath Extract Effervescent Tablet and its preparation method, so as to improve the problems of existing Five-Flavor Sweet Dew Bath Preparations being cumbersome to use, slow to disperse, and inconvenient to store and carry.

[0005] To achieve the above objectives, the present invention adopts the following technical solution.

[0006] In one embodiment, a Five-Flavor Sweet Dew Bath Extract Effervescent Tablet of the present invention comprises, by weight percentage, 15%–25% Five-Flavor Sweet Dew Bath Extract, 55% Effervescent Agent, 1%–4% Croscarmellose Sodium, 1%–4% Magnesium Stearate, and 16%–26% Excipients. The effervescent agent is citric acid and sodium bicarbonate; the excipients are microcrystalline cellulose, pregelatinized starch, and sodium carboxymethyl starch. The Five-Flavor Sweet Dew Bath Extract is prepared by water extraction, concentration, and drying of medicinal materials such as Juniperus chinensis, Rhododendron simsii, Myrica rubra, Artemisia capillaris, Ephedra sinica, Celtis sinensis, Polygonatum sibiricum, Tribulus terrestris, Asparagus cochinchinensis, Nardostachys jatamansi, Terminalia chebula, Phyllanthus emblica, Terminalia chebula, and Mirabilis jalapa.

[0007] In some embodiments, the effervescent tablet comprises, by weight percentage, 20% of Five Flavors Dew Bath Extract, 55% of Effervescent Agent, 2% of Cross-linked Carboxymethyl Cellulose Sodium, 2% of Magnesium Stearate, and 21% of Excipients.

[0008] In some embodiments, the weight ratio of citric acid to sodium bicarbonate in the effervescent agent is (1:1) to (1:1.3).

[0009] Preferably, the weight ratio of citric acid to sodium bicarbonate is 1:1.2.

[0010] In some embodiments, the excipients are microcrystalline cellulose, pregelatinized starch, and sodium carboxymethyl starch.

[0011] Preferably, the weight ratio of the microcrystalline cellulose, pregelatinized starch, and sodium carboxymethyl starch is 1:1:1.

[0012] In some embodiments, the Five-Flavor Sweet Dew Bath Extract of the present invention is made from the following medicinal materials in parts by weight: 10 parts of Juniperus chinensis, 10 parts of Rhododendron simsii, 10 parts of Artemisia capillaris, 10 parts of Ephedra sinica, 10 parts of Myrica rubra, 10 parts of Celtis sinensis, 1 part of Polygonatum sibiricum, 1 part of Tribulus terrestris, 1 part of Asparagus cochinchinensis, 1 part of Nardostachys jatamansi, 1 part of Mirabilis jalapa, 0.5 parts of Terminalia chebula, 0.5 parts of Phyllanthus emblica, and 0.5 parts of Terminalia chebula.

[0013] In some preferred embodiments, the Five-Flavor Sweet Dew Bath Extract Powder is prepared from the following medicinal materials by weight: 700g of Juniperus chinensis, 700g of Rhododendron simsii, 700g of Artemisia argyi, 700g of Ephedra sinica, 700g of Myrica rubra, 700g of Celery scabra, 70g of Polygonatum sibiricum, 70g of Tribulus terrestris, 70g of Asparagus cochinchinensis, 70g of Nardostachys jatamansi, 35g of Terminalia chebula, 35g of Phyllanthus emblica, 35g of Terminalia chebula, and 70g of Mirabilis jalapa.

[0014] In another preferred embodiment, the Five-Flavor Sweet Dew Bath Extract is prepared from the following medicinal materials in parts by weight: Juniperus chinensis 664.17g, Rhododendron simsii 664.17g, Artemisia capillaris 664.17g, Ephedra sinica 664.17g, Myrica rubra 664.17g, Celery scabra 664.17g, Polygonatum sibiricum 66.42g, Tribulus terrestris 66.42g, Asparagus cochinchinensis 66.42g, Nardostachys jatamansi 66.42g, Terminalia chebula 33.21g, Phyllanthus emblica 33.21g, Terminalia chebula 33.21g, Mirabilis jalapa 66.42g.

[0015] In another embodiment, the present invention also provides a method for preparing the above-mentioned Five-Flavor Sweet Dew Bath Extract Effervescent Tablets, comprising the following steps: 1) Take juniper, rhododendron, water cypress branch, large-seeded artemisia, ephedra, celery, polygonatum, tribulus, asparagus, nard, chebula, amla, chebula and Himalayan four o'clock flower, remove impurities and crush them; 2) Add water to extract the pulverized medicinal materials, combine the extracts, filter, concentrate and dry under reduced pressure, pulverize and sieve to obtain Five Flavors Sweet Dew Bath Extract Powder; 3) The extract powder is mixed with citric acid, sodium bicarbonate, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, croscarmellose sodium and magnesium stearate, and then granulated and compressed by dry method to obtain Wuwei Ganlu medicinal bath extract effervescent tablets.

[0016] Preferably, the water extraction in step 2) is as follows: for the first time, add 12 times the amount of water, soak for 3 hours, and decoct for 2 hours; for the second and third times, add 10 times the amount of water respectively, and decoct for 1 hour each time.

[0017] Preferably, in step 2), the relative density of the extract is 1.27 to 1.30 when it is concentrated to 50°C.

[0018] Preferably, the conditions for vacuum drying are: vacuum degree -0.07 to -0.08 MPa, temperature 75 to 80°C.

[0019] Preferably, the extract after vacuum drying is pulverized and passed through a 100-mesh sieve.

[0020] Compared with traditional Five Flavors Sweet Dew Medicated Bath Powder, this invention combines water-extracted extract powder with effervescent agents and molding excipients, and adopts dry granulation and tableting processes. The resulting effervescent tablets can quickly effervescently disintegrate and disperse evenly in warm water, and have the advantages of good formability, simple operation before use, and easy storage and carrying. Detailed Implementation

[0021] The following embodiments are used to further illustrate the present invention, but should not be construed as limiting the scope of protection of the present invention. Equivalent substitutions or corresponding improvements made by those skilled in the art without departing from the concept of the present invention should fall within the scope of protection of the present invention.

[0022] Example 1 Extraction Process The prescription for Five-Flavor Sweet Dew Bath is as follows: 700 g of Juniperus chinensis, 700 g of Rhododendron simsii, 700 g of Artemisia argyi, 700 g of Ephedra sinica, 700 g of Myrica rubra, 700 g of Celery scabra, 70 g of Polygonatum sibiricum, 70 g of Tribulus terrestris, 70 g of Asparagus cochinchinensis, 70 g of Nardostachys jatamansi, 35 g of Terminalia chebula, 35 g of Phyllanthus emblica, 35 g of Terminalia chebula, and 70 g of Mirabilis jalapa.

[0023] Preparation process: 1. Herbal Processing: Take Juniperus chinensis, Rhododendron simsii, Myrica rubra, Artemisia capillaris, Ephedra sinica, Celtis sinensis, Polygonatum sibiricum, Tribulus terrestris, Asparagus cochinchinensis, Nardostachys jatamansi, Terminalia chebula, Phyllanthus emblica, Terminalia chebula, and Mirabilis jalapa, and remove impurities. Spread the herbs to a thickness of no more than 5 cm and irradiate them under a UV lamp for 360–480 min, turning them over every 30 min. After irradiation, pulverize them and set aside.

[0024] 2. Extraction: Take the broken prescription herbs, add 12 times the amount of water, soak for 3 hours, and then heat and decoct for 2 hours. Filter the solution to obtain the filtrate. Add 10 times the amount of water to the dregs and heat and boil for 1 hour. Filter the solution to obtain the filtrate. Add 10 times the amount of water to the dregs for a third time and boil for 1 hour. Filter the solution and take the filtrate. Combine the filtrate obtained from the first two times to obtain the decoction.

[0025] 3. Concentration and Drying: The decoction is heated and concentrated to a relative density of 1.27–1.30 (50℃). The concentrated solution is then dried under reduced pressure at 75–80℃ and a vacuum of -0.07–-0.08 MPa. The resulting dry extract is pulverized and passed through a 100-mesh sieve to obtain extract powder.

[0026] Example 2: Five-Flavor Herbal Bath Effervescent Tablets Based on the material characteristics of the extract powder obtained in Example 1 and the preliminary screening results of excipients, citric acid, sodium bicarbonate, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, croscarmellose sodium, and magnesium stearate were selected as excipients. The effects of the amount of extract powder, the mass ratio of citric acid to sodium bicarbonate, and the amount of other excipients on the effervescent tablet forming quality were investigated. The amounts of croscarmellose sodium and magnesium stearate were both fixed at 2%, and the mass ratio of microcrystalline cellulose, pregelatinized starch, and sodium carboxymethyl starch was initially set at 1:1:1. Disintegration time, dispersion state, gas production effect, and appearance were used as evaluation indicators, with each indicator having a full score of 25 points. The comprehensive scoring method is shown in Table 1.

[0027] Table 1. Comprehensive Evaluation Table for Effervescent Tablets

[0028] Orthogonal experimental design for molding process research To screen the formulation of Wuwei Ganlu medicinal bath extract effervescent tablets, the amount of extract powder (A), the mass ratio of citric acid to sodium bicarbonate (B), and the amounts of other excipients (C) were used as factors of consideration, with a blank factor (D) included. The L9(3) method was employed. 4 The experiment was conducted using an orthogonal array, with the comprehensive score as the evaluation index. The factor levels and orthogonal experimental arrangement are shown in Tables 2 and 3, and the experimental results and analysis are shown in Tables 4 and 5.

[0029] Table 2 Experimental Factor Levels

[0030] Table 3 Orthogonal Experimental Design

[0031] Table 4. Statistical Table of Orthogonal Experiments

[0032] Table 5. Analysis of Variance for Orthogonal Experiments

[0033] P<0.05; F0.05(2,2)=19.00, F0.01(2,2)=99.00.

[0034] Table 4 shows that the range R-values ​​of each factor follow the order A > B > C > D, indicating that within the scope of the study, the order of influence of each factor on the overall score of Wuwei Ganlu medicinal bath extract effervescent tablets is: extract powder amount > acid-base ratio > other excipient amounts > blank factor. Among them, factor A has the largest range, indicating that the amount of extract powder has the most significant impact on the quality of effervescent tablet formation; factor B is next; and factor C has a relatively smaller impact.

[0035] Table 4 shows that the order of the range R values ​​for each factor is A > B > C > D, indicating that within the scope of this experiment, the order of influence of each factor on the overall score is: amount of extract powder > mass ratio of citric acid to sodium bicarbonate > amount of other excipients > blank factor. A visual analysis based on the k values ​​of each factor reveals that the optimal combination is A2B2C3. Given that the total amount of each component in the formulation should be 100% by mass percentage, and that there is a proportional relationship between the amount of extract powder and other excipients, the final formulation combination still needs to be confirmed based on the actual supplementation methods of each experimental formulation and the original experimental records. Based on the formulations used in the existing validation experiments, the example uses the A2B2C2 combination as the validation formulation.

[0036] Analysis of variance was performed on the data listed in Table 5. The F-value for factor A was 29.0400, which is greater than F0.05(2,2) = 19.00 but less than F0.01(2,2) = 99.00, indicating that factor A is statistically significant at the α = 0.05 level. The F-values ​​for factors B and C were 4.3625 and 1.9837, respectively, neither of which reached the α = 0.05 level. Given the low degrees of freedom of error in this experiment and the possibility that the total prescription constraint may affect the independence of factors, the statistical results are only for prescription screening reference, and the final process will be based on the results of the validation experiment.

[0037] Based on existing validation tests, the effervescent tablet formulation and manufacturing process are as follows: 20 g of extract powder, 25 g of citric acid, 30 g of sodium bicarbonate, 7 g of microcrystalline cellulose, 7 g of pregelatinized starch, 7 g of sodium carboxymethyl starch, 2 g of cross-linked sodium carboxymethyl cellulose, and 2 g of magnesium stearate; after mixing all materials evenly, dry granulation and tableting are performed to obtain the final product.

[0038] Process verification test Based on the results of orthogonal experiments, and combined with the formulation coordination, formulation formability and production practice, the optimal formulation process for Wuwei Ganlu medicinal bath extract effervescent tablets was determined as follows: Take 20 g of extract powder, add 25 g of citric acid, 30 g of sodium bicarbonate, 7 g of microcrystalline cellulose, 7 g of pregelatinized starch, 7 g of sodium carboxymethyl starch, 2 g of cross-linked sodium carboxymethyl cellulose and 2 g of magnesium stearate, mix evenly, and then granulate and compress the mixture using a dry method to obtain the final product.

[0039] Three batches of validation tests were conducted according to the above-mentioned optimized molding formulation process, and the particle yield and repeatability were calculated. The results are shown in Table 6. The particle yields of the three batches of samples were 99.6%, 99.7%, and 99.5%, respectively, with an average of 99.6% and an RSD of 0.1%, indicating that the process is stable and has good repeatability.

[0040] Table 6 Results of Molding Process Verification Tests

[0041] Table 6 shows that the particle yield of the three batches of samples was 99.5%–99.7%, with an average of 99.6% and an RSD of 0.1%, indicating that the process had good repeatability in the tested batches.

[0042] Meanwhile, the effervescent tablets prepared according to the above-mentioned prescription process were examined for effervescent disintegration time, dispersion state, gas production effect and appearance.

[0043] The Five-Flavor Dew Bath Extract Effervescent Tablets prepared by this invention can rapidly generate continuous and uniform bubbles in water at 40℃~45℃, with effervescence completion time less than 2 minutes. After effervescence, the tablets basically disintegrate, and the liquid is brownish-yellow to brownish-brown, with relatively uniform dispersion. No obvious hard core, large floating particles, or agglomeration are observed, indicating that the preparation has good effervescent disintegration performance and immediate dispersibility.

[0044] Specific results: The disintegration times of the three batches of samples were 1.58 min, 1.71 min, and 1.64 min, respectively, with an average disintegration time of 1.64 min, all of which were completed within 2 minutes. When the samples were added to warm water, the tablets disintegrated and dispersed rapidly, producing uniform and continuous gas with abundant bubbles, lasting approximately 1.5–2.0 min. The resulting solution was yellowish-brown, relatively homogeneous, and showed no obvious clumping after standing. A small amount of fine suspended matter was visible, but no large particles were visible to the naked eye. The resulting effervescent tablets were intact, relatively uniform in thickness, with a smooth surface and neat edges, without cracks, loose tablets, obvious missing edges or corners, or significant powdering. This indicates that the effervescent tablets produced by this formulation process have good formability and performance characteristics.

[0045] Summary of the research on the process of Five-Flavor Sweet Dew Medicated Bath Extract Effervescent Tablets: The first soaking was done with 12 times the amount of water for 3 hours, followed by decocting for 2 hours. The second and third soakings were done with 10 times the amount of water for 1 hour each. The decoctions were combined, filtered, and concentrated until the relative density at 50°C was 1.27–1.30. The decoction was then dried under reduced pressure at a vacuum of -0.07–0.08 MPa and a temperature of 75–80°C. The powder was then pulverized and passed through a 100-mesh sieve to obtain the Five Flavors Sweet Dew Bath Extract Powder. Citric acid, sodium bicarbonate, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, croscarmellose sodium, and magnesium stearate were added to the extract powder. After mixing evenly, the mixture was granulated by dry method and compressed into tablets to obtain the Five Flavors Sweet Dew Bath Extract Effervescent Tablets.

[0046] The preferred formulation for effervescent tablets is as follows: 20% extract powder, 55% total effervescent agent, with a citric acid to sodium bicarbonate mass ratio of 1:1.2, 21% other excipients, 2% croscarmellose sodium, and 2% magnesium stearate; the mass ratio of microcrystalline cellulose, pregelatinized starch, and sodium carboxymethyl starch in the excipients is 1:1:1. Effervescent tablets prepared using this formulation have an average disintegration time of 1.64 min, uniform and continuous gas production, a yellow-brown solution, relatively uniform dispersion, and no obvious large particle residue; the tablets are intact, with a relatively smooth surface and good formability. This indicates that the effervescent tablets obtained by this process have controllable quality, stable process, and are convenient to use, store, and carry.

[0047] Example 3: Five-Flavor Sweet Dew Effervescent Tablets Based on the results of the process research, combined with the yield, excipient dosage, and dosage form (0.5 g / tablet), the formulation and preparation process are as follows: prescription: Juniperus chinensis 664.17g, Rhododendron simsii 664.17g, Artemisia capillaris 664.17g Ephedra 664.17g, Bryus officinalis 664.17g, Celery shavings 664.17g Polygonatum 66.42g, Tribulus terrestris 66.42g, Asparagus cochinchinensis 66.42g Nardostachys chinensis 66.42g, Terminalia chebula 33.21g, Phyllanthus emblica 33.21g Terminalia chebula 33.21g, Mirabilis jalapa 66.42g (or these ingredients in parts by weight).

[0048] Preparation process: The prescription medicinal materials are decocted three times with water. For the first decoction, 12 times the amount of water is added, the herbs are soaked for 3 hours, and then decocted for 2 hours. For the second and third decoctions, 10 times the amount of water is added, and each decoction is decocted for 1 hour. The decoctions are combined, filtered, and the filtrate is concentrated to a relative density of 1.27–1.30 (50℃). The filtrate is then dried under reduced pressure (vacuum degree -0.07–-0.08 MPa, 75–80℃), pulverized, and passed through a 100-mesh sieve. 125g of citric acid, 150g of sodium bicarbonate, 35g of microcrystalline cellulose, 35g of pregelatinized starch, 35g of sodium carboxymethyl starch, 10g of croscarmellose sodium, and 10g of magnesium stearate are added. The mixture is then granulated by dry method and compressed into 1000 tablets.

Claims

1. A five-flavor sweet dew medicinal bath extract effervescent tablet, characterized in that, The extract comprises, by mass percentage, 15%–25% of Five-Flavor Sweet Dew Bath Extract Powder, 55% of effervescent agent, 1%–4% of croscarmellose sodium cellulose, 1%–4% of magnesium stearate, and 16%–26% of excipients, with the sum of the mass percentages of all components being 100%. The effervescent agent is composed of citric acid and sodium bicarbonate. The Five-Flavor Sweet Dew Bath Extract Powder is prepared by water extraction, concentration, and drying of Juniperus chinensis, Rhododendron simsii, Myrica rubra, Artemisia capillaris, Ephedra sinica, Celtis sinensis, Polygonatum sibiricum, Tribulus terrestris, Asparagus cochinchinensis, Nardostachys jatamansi, Terminalia chebula, Phyllanthus emblica, Terminalia chebula, and Mirabilis jalapa.

2. The Five-Flavor Sweet Dew Bath Extract Effervescent Tablet according to claim 1, characterized in that, By weight percentage, it includes 20% Five Flavors Sweet Dew Bath Extract Powder, 55% Effervescent Agent, 2% Croscarmellose Sodium, 2% Magnesium Stearate, and 21% Excipients.

3. The Five-Flavor Sweet Dew Bath Extract Effervescent Tablet according to claim 1 or 2, characterized in that, The mass ratio of citric acid to sodium bicarbonate is (1:1) to (1:1.3).

4. The Five-Flavor Sweet Dew Bath Extract Effervescent Tablet according to claim 3, characterized in that, The mass ratio of citric acid to sodium bicarbonate is 1:1.

2.

5. The Five-Flavor Sweet Dew Bath Extract Effervescent Tablet according to claim 1 or 2, characterized in that, The excipients consist of microcrystalline cellulose, pregelatinized starch, and sodium carboxymethyl starch.

6. The Five-Flavor Sweet Dew Bath Extract Effervescent Tablet according to claim 5, characterized in that, The mass ratio of the microcrystalline cellulose, pregelatinized starch, and sodium carboxymethyl starch is 1:1:

1.

7. The Five-Flavor Sweet Dew Bath Extract Effervescent Tablet according to claim 1 or 2, characterized in that, The Five-Flavor Sweet Dew Bath Extract Powder is prepared from the following medicinal materials in parts by weight: Juniperus chinensis 10 parts, Rhododendron simsii 10 parts, Artemisia capillaris 10 parts, Ephedra sinica 10 parts, Myrica rubra 10 parts, Celery scabra 10 parts, Polygonatum sibiricum 1 part, Tribulus terrestris 1 part, Asparagus cochinchinensis 1 part, Nardostachys jatamansi 1 part, Mirabilis jalapa 1 part, Terminalia chebula 0.5 parts, Phyllanthus emblica 0.5 parts, Terminalia chebula 0.5 parts.

8. A method for preparing the Five-Flavor Sweet Dew Bath Extract Effervescent Tablets according to any one of claims 1 to 7, characterized in that, Includes the following steps: (1) Take juniper, rhododendron, water cypress branch, large seed wormwood, ephedra, celery, polygonatum, tribulus, asparagus, nard, chebula, amla, chebula and Himalayan four o'clock, remove impurities and crush them; (2) Add water to extract the pulverized medicinal materials, combine the extracts, filter, concentrate and dry under reduced pressure, pulverize and sieve to obtain Five Flavors Sweet Dew Bath Extract Powder; (3) The Five Flavors Sweet Dew Bath Extract Powder is mixed with citric acid, sodium bicarbonate, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose and magnesium stearate, then granulated by dry method and compressed into tablets to obtain the final product.

9. The preparation method according to claim 8, characterized in that, The water extraction in step (2) includes: first, adding 12 times the total mass of the medicinal materials to water, soaking for 3 hours, and decocting for 2 hours; second and third, adding 10 times the total mass of the medicinal materials to water respectively, and decocting for 1 hour each.

10. The preparation method according to claim 8 or 9, characterized in that, In step (2), the extract is concentrated to a relative density of 1.27 to 1.30 when measured at 50°C. Then, it is dried under reduced pressure at a vacuum of -0.07 to -0.08 MPa and a temperature of 75 to 80°C. The resulting dry extract is then pulverized and passed through a 100-mesh sieve.

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