Tibetan medicine bath effervescent composition and preparation method thereof

Abstract

The invention discloses a Tibetan medicine bath effervescent composition and a preparation method thereof. The effervescent composition prepared by the invention consists of a medicated bath layer and an effervescent layer, and comprises the following components in parts by weight: 30-60 parts of a five-flavor sweet dew soup beta-cyclodextrin microencapsulated inclusion compound, 15-35 parts of citric acid, 25-50 parts of sodium bicarbonate and the like. The preparation method comprises the following steps: firstly, carrying out extraction and alcohol precipitation on a Wuwei mannan decoction raw medicinal material, and then carrying out microencapsulation inclusion on the Wuwei mannan decoction raw medicinal material and volatile oil by using beta-cyclodextrin; preparing the inclusion compound, citric acid and auxiliary materials into medicated bath layer particles, and preparing sodium bicarbonate and auxiliary materials into effervescent layer particles; and finally, mixing the two kinds of particles with a lubricant, and tabletting by adopting a double-layer tabletting machine. The effervescent composition is moderate in effervescent time (85.3-104.1 s), good in solubility, high in hardness (greater than 72 N) and low in friability (less than 0.32%), the retention rate of volatile oil is up to 92% or above, the retention rate of total flavonoids is up to 95% or above, and the shelf life is prolonged.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, and in particular to a Tibetan medicine bath effervescent composition and its preparation method. Background Technology

[0002] Tibetan medicinal baths are a widely used traditional therapy in Tibetan medicine's external treatment methods. The medicinal components are absorbed through the skin and penetrate the body, achieving effects such as clearing heat and detoxifying, promoting blood circulation and removing blood stasis, relaxing muscles and tendons, and dispelling wind and dampness. Traditional Tibetan medicinal baths often involve directly bathing in a decocted medicinal liquid. While the efficacy is definite, problems such as cumbersome preparation, unstable medicinal components, short shelf life, and inconvenience in carrying make standardized production and modern promotion difficult. To improve ease of use, in recent years, some scholars have attempted to formulate Tibetan medicinal baths into solid preparations such as granules, effervescent tablets, or bath salts. However, due to the complex composition of Tibetan medicinal materials, their volatility, and susceptibility to oxidation, traditional tableting processes often lead to the loss of effective components and a weakening of the bath's effect. On the other hand, effervescent tablet technology, due to its ability to rapidly release medicinal components in water and generate bubbles to promote diffusion, is widely used in pharmaceuticals, health products, and personal care products. Existing effervescent preparations for medicinal baths typically use a simple organic acid-carbonate reaction system (such as citric acid-sodium bicarbonate), supplemented with some plant extracts. However, these preparations still have problems such as uneven drug dissolution, easy decomposition of active substances by moisture, and easy loss of aroma or volatile oils. Furthermore, they lack stabilization and sustained-release control technologies for various components in Tibetan medicine compound preparations. Summary of the Invention

[0003] To address the aforementioned issues, this invention proposes a Tibetan medicine bath effervescent composition and its preparation method. By using β-cyclodextrin microencapsulation technology to simultaneously encapsulate the volatile oil and total extract of Wuwei Ganlu Decoction, and combining it with a double-layer tablet structure of bath layer and effervescent layer, stable protection and graded release of the active pharmaceutical ingredients are achieved, making the Tibetan medicine bath preparation combine traditional efficacy with modern ease of use.

[0004] The present invention proposes a Tibetan medicine bath effervescent composition comprising the following components in parts by weight: 30-60 parts of Wuwei Ganlu Tang β-cyclodextrin microcapsule inclusion complex, 15-35 parts of citric acid, 20-40 parts of first diluent, 1-3 parts of first lubricant, 25-50 parts of sodium bicarbonate, 20-45 parts of second diluent, and 1-3 parts of second lubricant; the composition comprises a bath layer and an effervescent layer.

[0005] The present invention provides a method for preparing a Tibetan medicine bath effervescent composition, comprising the following steps: Step 1: Weigh the raw medicinal materials of Wuwei Ganlu Decoction, extract the volatile oil, and obtain the total extract after water extraction and alcohol precipitation; dissolve β-cyclodextrin in water, add it to the mixture of volatile oil and total extract to carry out inclusion reaction, cool, filter and dry to obtain Wuwei Ganlu Decoction β-cyclodextrin microencapsulated inclusion complex. Step 2: Mix the β-cyclodextrin microcapsule inclusion complex of Wuwei Ganlu Decoction, citric acid, and the first diluent, use pure water as a binder to form a soft material, sieve and granulate, and dry to obtain medicinal bath layer particles; Step 3: Mix sodium bicarbonate and the second diluent, use ethanol as a binder to form a soft material, sieve and granulate, dry to obtain effervescent layer particles; Step 4: Mix the medicated bath granules with the first lubricant and the effervescent layer granules with the second lubricant. Use a double-layer tablet press to fill the two layers of materials sequentially and compress them into tablets to obtain the Tibetan medicine bath effervescent composition.

[0006] Preferably, the weight composition of the original medicinal materials of Wuwei Ganlu Decoction in step 1 is as follows: 20-40 parts of Rhododendron simsii, 15-30 parts of Artemisia argyi, 20-40 parts of Ephedra sinica, 20-40 parts of Cypress twigs, and 20-40 parts of Artemisia argyi.

[0007] Preferably, the inclusion reaction in step 1 is carried out at a temperature of 40-60°C for 1-3 hours.

[0008] Preferably, the drying temperature in steps 2 and 3 is 40-60℃, and the moisture content of the dried particles is 1.0-2.5%.

[0009] Preferably, both the first and second diluents are mannitol.

[0010] Preferably, both the first lubricant and the second lubricant are polyethylene glycol 6000.

[0011] Preferably, in step 4, the mass ratio of the medicinal bath particles, the first lubricant, the effervescent layer particles, and the first lubricant is 10:(0.05-0.1):10:(0.05-0.1).

[0012] Preferably, the tablet hardness in step 4 is 70-120 N and the tablet weight is 3-8 g.

[0013] The present invention provides a Tibetan medicine bath effervescent composition, which is prepared by the above-described method.

[0014] The beneficial effects of this invention are: This invention combines β-cyclodextrin microencapsulation technology with a bilayer tableting structure consisting of a medicated bath and an effervescent layer, significantly improving the overall performance of the product: the stability of active ingredients such as volatile oils and total flavonoids is effectively enhanced, with retention rates of over 92% and 95% respectively after 3 months; the physical properties of the tablets are improved, with a hardness higher than 72 N and a friability of less than 0.32%; the user experience is improved, with a moderate effervescence time (85.3s-104.1s), a weakly acidic solution pH, and no oil droplets floating or settling. This invention significantly improves product stability and makes it easier to carry and use. Attached Figure Description

[0015] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings:

[0016] Figure 1 Images showing the physical properties of Tibetan medicine effervescent bath compositions; Figure 2 Images showing the effervescent and dissolution properties of Tibetan medicine bath effervescent compositions; Figure 3 Images showing the stability and retention rate of volatile oils in Tibetan medicine bath effervescent compositions; Figure 4 Images showing the stability and retention rate of total flavonoids in Tibetan medicine bath effervescent compositions. Detailed Implementation

[0017] The following provides a detailed description of the embodiments of the present invention: These embodiments are implemented based on the technical solution of the present invention, and provide detailed implementation methods and processes. However, the scope of protection of the present invention is not limited to the following embodiments. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions.

[0018] Example 1 A Tibetan medicine bath effervescent composition comprises the following components in parts by weight: 30 parts of Wuwei Ganlu Tang β-cyclodextrin microcapsule inclusion complex, 15 parts of citric acid, 20 parts of first diluent, 1 part of first lubricant, 25 parts of sodium bicarbonate, 20 parts of second diluent, and 1 part of second lubricant; the composition comprises a bath layer and an effervescent layer.

[0019] The preparation method of the Tibetan medicine bath effervescent composition in this embodiment includes the following steps: Step 1: Weigh 20 parts of Rhododendron simsii, 15 parts of Artemisia annua, 20 parts of Ephedra sinica, 20 parts of Myrica rubra, and 20 parts of Artemisia argyi. Extract the volatile oils, add 150 mL of water and decoct twice (1.5 h the first time, 1 h the second time). Combine the filtrates and concentrate under reduced pressure to an aqueous extract at 60℃ with a relative density of 1.20. Slowly add anhydrous ethanol to the aqueous extract to make the ethanol volume fraction of the solution reach 70%. Stir evenly and let stand for 12 h. Filter and collect the supernatant. Recover the ethanol and concentrate under reduced pressure to obtain the total extract of Wuwei Ganlu Decoction. Dissolve β-cyclodextrin in water and add it to the mixture of volatile oil and total extract. Incubate the mixture at 40℃ for 3 h for inclusion reaction. After cooling, filter and dry to obtain the β-cyclodextrin microencapsulated inclusion complex of Wuwei Ganlu Decoction.

[0020] Step 2: Mix the β-cyclodextrin microcapsule complex of Wuwei Ganlu Decoction, citric acid, and mannitol, use pure water as a binder to form a soft material, sieve and granulate, and dry at 40°C to obtain medicinal bath layer particles with a moisture content of 1.0%.

[0021] Step 3: Mix sodium bicarbonate and mannitol, use ethanol as a binder to form a soft material, sieve and granulate, dry at 40°C to obtain effervescent layer particles with a water content of 1.0%.

[0022] Step 4: Mix 10 g of bath granules with 0.05 g of polyethylene glycol 6000, and mix 10 g of effervescent granules with 0.05 g of polyethylene glycol 6000. Use a double-layer tablet press to fill the two layers of materials in sequence, compress the tablets, and the tablet hardness is 70 N and the tablet weight is 3 g to obtain the Tibetan medicine bath effervescent composition.

[0023] Example 2 A Tibetan medicine bath effervescent composition comprises the following components in parts by weight: 40 parts of Wuwei Ganlu Tang β-cyclodextrin microcapsule inclusion complex, 35 parts of citric acid, 40 parts of first diluent, 3 parts of first lubricant, 50 parts of sodium bicarbonate, 45 parts of second diluent, and 3 parts of second lubricant; the composition comprises a bath layer and an effervescent layer.

[0024] The preparation method of the Tibetan medicine bath effervescent composition in this embodiment includes the following steps: Step 1: Weigh 40 parts of Rhododendron simsii, 30 parts of Artemisia capillaris, 40 parts of Ephedra sinica, 40 parts of Myrica rubra, and 40 parts of Artemisia argyi. Extract the volatile oils, add 150 mL of water and decoct twice (2 hours the first time, 1 hour the second time). Combine the filtrates and concentrate under reduced pressure to an aqueous extract at 60°C and a relative density of 1.10. Slowly add anhydrous ethanol to the aqueous extract until the ethanol volume fraction reaches 80%. Stir well and let stand for 24 hours. Filter and collect the supernatant. Recover the ethanol and concentrate under reduced pressure to obtain the total extract of Wuwei Ganlu Tang. Dissolve β-cyclodextrin in water and add it to the mixture of volatile oil and total extract. Incubate the mixture at 60°C for 1 hour. After cooling, filter and dry to obtain the β-cyclodextrin microencapsulated inclusion complex of Wuwei Ganlu Tang.

[0025] Step 2: Mix the β-cyclodextrin microcapsule complex of Wuwei Ganlu Decoction, citric acid, and mannitol, use pure water as a binder to form a soft material, sieve and granulate, and dry at 60°C to obtain medicinal bath layer particles with a moisture content of 2.5%.

[0026] Step 3: Mix sodium bicarbonate and mannitol, use ethanol as a binder to form a soft material, sieve and granulate, dry at 60°C to obtain effervescent layer particles with a water content of 2.5%.

[0027] Step 4: Mix 10 g of bath granules with 0.1 g of polyethylene glycol 6000, and mix 10 g of effervescent granules with 0.1 g of polyethylene glycol 6000. Use a double-layer tablet press to fill the two layers of materials in sequence, compress the tablets, and the tablet hardness is 120 N and the tablet weight is 8 g to obtain the Tibetan medicine bath effervescent composition.

[0028] Example 3 A Tibetan medicine bath effervescent composition comprises the following components in parts by weight: 50 parts of Wuwei Ganlu Tang β-cyclodextrin microcapsule inclusion complex, 25 parts of citric acid, 30 parts of first diluent, 2 parts of first lubricant, 37.5 parts of sodium bicarbonate, 32.5 parts of second diluent, and 2 parts of second lubricant; the composition comprises a bath layer and an effervescent layer.

[0029] The preparation method of the Tibetan medicine bath effervescent composition in this embodiment includes the following steps: Step 1: Weigh 30 parts of Rhododendron simsii, 22.5 parts of Artemisia annua, 30 parts of Ephedra sinica, 30 parts of Myrica rubra, and 30 parts of Artemisia argyi. Extract the volatile oils, add 150 mL of water and decoct twice (2 hours the first time, 1 hour the second time). Combine the filtrates and concentrate under reduced pressure to an aqueous extract at 60°C and a relative density of 1.15. Slowly add anhydrous ethanol to the aqueous extract until the ethanol volume fraction reaches 80%. Stir well and let stand for 18 hours. Filter and collect the supernatant. Recover the ethanol and concentrate under reduced pressure to obtain the total extract of Wuwei Ganlu Tang. Dissolve β-cyclodextrin in water and add it to the mixture of volatile oil and total extract. Incubate the mixture at 50°C for 2 hours for inclusion reaction. After cooling, filter and dry to obtain the β-cyclodextrin microencapsulated inclusion complex of Wuwei Ganlu Tang.

[0030] Step 2: Mix the β-cyclodextrin microcapsule complex of Wuwei Ganlu Decoction, citric acid, and mannitol, use pure water as a binder to form a soft material, sieve and granulate, and dry at 50°C to obtain medicinal bath layer particles with a water content of 1.75%.

[0031] Step 3: Mix sodium bicarbonate and mannitol, use ethanol as a binder to form a soft material, sieve and granulate, dry at 50°C to obtain effervescent layer particles with a water content of 1.75%.

[0032] Step 4: Mix 10 g of bath granules with 0.075 g of polyethylene glycol 6000, and mix 10 g of effervescent granules with 0.075 g of polyethylene glycol 6000. Use a double-layer tablet press to fill the two layers of materials sequentially, compress the tablets, and the tablet hardness is 95 N with a tablet weight of 5.5 g to obtain the Tibetan medicine bath effervescent composition.

[0033] Example 4 A Tibetan medicine bath effervescent composition comprises the following components in parts by weight: 60 parts of Wuwei Ganlu Tang β-cyclodextrin microcapsule inclusion complex, 35 parts of citric acid, 20 parts of first diluent, 3 parts of first lubricant, 25 parts of sodium bicarbonate, 45 parts of second diluent, and 3 parts of second lubricant; the composition comprises a bath layer and an effervescent layer.

[0034] The preparation method of the Tibetan medicine bath effervescent composition in this embodiment includes the following steps: Step 1: Weigh 40 parts of Rhododendron simsii, 15 parts of Artemisia capillaris, 40 parts of Ephedra sinica, 40 parts of Myrica rubra, and 20 parts of Artemisia argyi. Extract the volatile oils, add 150 mL of water and decoct twice (2 hours the first time, 1 hour the second time). Combine the filtrates and concentrate under reduced pressure to an aqueous extract at 60°C and a relative density of 1.20. Slowly add anhydrous ethanol to the aqueous extract until the ethanol volume fraction reaches 80%. Stir well and let stand for 12 hours. Filter and collect the supernatant. Recover the ethanol and concentrate under reduced pressure to obtain the total extract of Wuwei Ganlu Tang. Dissolve β-cyclodextrin in water and add it to the mixture of volatile oil and total extract. Incubate the mixture at 40°C for 3 hours for inclusion reaction. After cooling, filter and dry to obtain the β-cyclodextrin microencapsulated inclusion complex of Wuwei Ganlu Tang.

[0035] Step 2: Mix the β-cyclodextrin microcapsule complex of Wuwei Ganlu Decoction, citric acid, and mannitol, use pure water as a binder to form a soft material, sieve and granulate, and dry at 60℃ to obtain medicinal bath layer particles with a moisture content of 1.0%.

[0036] Step 3: Mix sodium bicarbonate and mannitol, use ethanol as a binder to form a soft material, sieve and granulate, dry at 60°C to obtain effervescent layer particles with a water content of 2.5%.

[0037] Step 4: Mix 10 g of bath granules with 0.05 g of polyethylene glycol 6000, and mix 10 g of effervescent granules with 0.1 g of polyethylene glycol 6000. Use a double-layer tablet press to fill the two layers of materials in sequence, compress the tablets, and the tablet hardness is 120 N and the tablet weight is 8 g to obtain the Tibetan medicine bath effervescent composition.

[0038] Comparative Example 1: The difference between this comparative example and Example 1 is that β-cyclodextrin inclusion is not performed, and the total extract of Wuwei Ganlu Decoction is directly mixed with volatile oil.

[0039] A Tibetan medicine bath effervescent composition comprises the following components in parts by weight: 30 parts of total extract-volatile oil mixture, 15 parts of citric acid, 20 parts of first diluent, 1 part of first lubricant, 25 parts of sodium bicarbonate, 20 parts of second diluent, and 1 part of second lubricant; the composition comprises a bath layer and an effervescent layer.

[0040] The preparation method of a Tibetan medicine bath effervescent composition in this comparative example includes the following steps: Step 1: Weigh 20 parts of Rhododendron simsii, 15 parts of Artemisia capillaris, 20 parts of Ephedra sinica, 20 parts of Myrica rubra, and 20 parts of Artemisia argyi. Extract the volatile oils, add 150 mL of water and decoct twice (1.5 h the first time, 1 h the second time). Combine the filtrates and concentrate under reduced pressure to an aqueous extract at 60℃ and a relative density of 1.20. Slowly add anhydrous ethanol to the aqueous extract until the ethanol volume fraction in the solution reaches 70%. Stir well and let stand for 12 h. Filter and collect the supernatant. Recover the ethanol and concentrate under reduced pressure to obtain the total extract of the Five-Flavor Decoction. Add the volatile oils and mix to obtain a mixture of the total extract of the Five-Flavor Decoction and the volatile oils.

[0041] Step 2: Mix the total extract-volatile oil mixture, citric acid, and mannitol, use pure water as a binder to form a soft material, sieve and granulate, and dry at 40°C to obtain a medicinal bath layer granule with a water content of 1.0%.

[0042] Step 3: Mix sodium bicarbonate and mannitol, use ethanol as a binder to form a soft material, sieve and granulate, dry at 40°C to obtain effervescent layer particles with a water content of 1.0%.

[0043] Step 4: Mix 10 g of bath granules with 0.05 g of polyethylene glycol 6000, and mix 10 g of effervescent granules with 0.05 g of polyethylene glycol 6000. Use a double-layer tablet press to fill the two layers of materials in sequence, compress the tablets, and the tablet hardness is 70 N and the tablet weight is 3 g to obtain the Tibetan medicine bath effervescent composition.

[0044] Comparative Example 2: The difference between this comparative example and Example 1 is that a single-layer compression tablet is used instead of a double-layer compression tablet.

[0045] A Tibetan medicine bath effervescent composition comprises the following components in parts by weight: 30 parts of Wuwei Ganlu Tang β-cyclodextrin microcapsule inclusion complex, 15 parts of citric acid, 20 parts of first diluent, 1 part of first lubricant, 25 parts of sodium bicarbonate, 20 parts of second diluent, and 1 part of second lubricant; the composition comprises a bath layer and an effervescent layer.

[0046] The preparation method of a Tibetan medicine bath effervescent composition in this comparative example includes the following steps: Step 1: Weigh 20 parts of Rhododendron simsii, 15 parts of Artemisia annua, 20 parts of Ephedra sinica, 20 parts of Myrica rubra, and 20 parts of Artemisia argyi. Extract the volatile oils, add 150 mL of water and decoct twice (1.5 h the first time, 1 h the second time). Combine the filtrates and concentrate under reduced pressure to an aqueous extract at 60℃ with a relative density of 1.20. Slowly add anhydrous ethanol to the aqueous extract to make the ethanol volume fraction of the solution reach 70%. Stir evenly and let stand for 12 h. Filter and collect the supernatant. Recover the ethanol and concentrate under reduced pressure to obtain the total extract of Wuwei Ganlu Decoction. Dissolve β-cyclodextrin in water and add it to the mixture of volatile oil and total extract. Incubate the mixture at 40℃ for 3 h for inclusion reaction. After cooling, filter and dry to obtain the β-cyclodextrin microencapsulated inclusion complex of Wuwei Ganlu Decoction.

[0047] Step 2: Mix the β-cyclodextrin microcapsule complex of Wuwei Ganlu Decoction, citric acid, and mannitol, use pure water as a binder to form a soft material, sieve and granulate, and dry at 40°C to obtain medicinal bath layer particles with a moisture content of 1.0%.

[0048] Step 3: Mix sodium bicarbonate and mannitol, use ethanol as a binder to form a soft material, sieve and granulate, dry at 40°C to obtain effervescent layer particles with a water content of 1.0%.

[0049] Step 4: Mix 10 g of bath granules with 0.05 g of polyethylene glycol 6000, and mix 10 g of effervescent granules with 0.05 g of polyethylene glycol 6000. Compress the mixture directly into tablets using a tablet press without stratification. The tablet hardness is 70 N and the tablet weight is 3 g, thus obtaining the Tibetan medicine bath effervescent composition.

[0050] Comparative Example 3: The difference between this comparative example and Example 1 is that ordinary dextrin is used instead of β-cyclodextrin.

[0051] A Tibetan medicine bath effervescent composition comprises the following components in parts by weight: 30 parts of Wuwei Ganlu Tang β-cyclodextrin microcapsule inclusion complex, 15 parts of citric acid, 20 parts of first diluent, 1 part of first lubricant, 25 parts of sodium bicarbonate, 20 parts of second diluent, and 1 part of second lubricant; the composition comprises a bath layer and an effervescent layer.

[0052] The preparation method of a Tibetan medicine bath effervescent composition in this comparative example includes the following steps: Step 1: Weigh 20 parts of Rhododendron simsii, 15 parts of Artemisia capillaris, 20 parts of Ephedra sinica, 20 parts of Myrica rubra, and 20 parts of Artemisia argyi. Extract the volatile oil, add 150 mL of water and decoct twice (1.5 h the first time, 1 h the second time). Combine the filtrates and concentrate under reduced pressure to an aqueous extract at 60℃ with a relative density of 1.20. Slowly add anhydrous ethanol to the aqueous extract to make the ethanol volume fraction of the solution reach 70%. Stir evenly and let stand for 12 h. Filter and collect the supernatant. Recover the ethanol and concentrate under reduced pressure to obtain the total extract of Wuwei Ganlu Tang. Dissolve β-cyclodextrin in water and add it to the mixture of volatile oil and total extract. Introduce an inclusion reaction at 40℃ for 3 h. After cooling, filter and dry to obtain a mixed powder of Wuwei Ganlu Tang and ordinary dextrin.

[0053] Step 2: Mix the Five Flavors Dew Decoction-Ordinary Dextrin Mixed Powder, Citric Acid, and Mannitol, use pure water as a binder to form a soft material, sieve and granulate, and dry at 40℃ to obtain medicinal bath layer particles with a moisture content of 1.0%.

[0054] Step 3: Mix sodium bicarbonate and mannitol, use ethanol as a binder to form a soft material, sieve and granulate, dry at 40°C to obtain effervescent layer particles with a water content of 1.0%.

[0055] Step 4: Mix 10 g of bath granules with 0.05 g of polyethylene glycol 6000, and mix 10 g of effervescent granules with 0.05 g of polyethylene glycol 6000. Use a double-layer tablet press to fill the two layers of materials in sequence, compress the tablets, and the tablet hardness is 70 N and the tablet weight is 3 g to obtain the Tibetan medicine bath effervescent composition.

[0056] Performance testing 1 Physical properties (1) Friability S1. Take 10 test samples, remove the surface powder with a brush, weigh them, and record the weight as W1. S2. Place the test sample into the cylinder of the friability tester, tighten the cylinder cap, rotate at 25 rpm for 4 minutes, remove the test sample, remove the fine powder on the surface with a brush, weigh it and record it as W2, calculate the friability, friability = (W1-W2) / W1×100%.

[0057] (2) Hardness S1. Turn on the hardness tester and perform zero-point calibration; S2. Randomly select 10 test samples. Place one sample upright between two pressure plates, start the instrument, and the pressure plates apply pressure to the tablet at a uniform speed until the tablet breaks. The instrument automatically records the maximum force value at the moment of breakage, in Newtons (N). Repeat the above operation for 10 test samples and calculate the average hardness of the 10 samples. The physical performance test results are shown in Table 1:

[0058] Table 1 Physical Performance Test Data

[0059] As shown in Table 1, the Tibetan medicine bath effervescent compositions prepared in Examples 1-4 have a friability of no more than 0.32% and an average hardness greater than 72.16 N, exhibiting good physical properties. This is because β-cyclodextrin simultaneously encapsulates the volatile oil and the total extract from the Five-Flavor Dew Soup, transforming them into stable solid powders, thus improving the physical properties of the composition. Combined with the double-layer tablet structure, it physically isolates citric acid and sodium bicarbonate, preventing pre-reaction and ensuring the integrity of the composition. In comparison, Comparative Example 1 did not involve β-cyclodextrin inclusion. The total extract of Wuwei Ganlu Decoction is typically hygroscopic and sticky. When mixed with citric acid for granulation, it easily softens and sticks the granules, resulting in poor compressibility and insufficient tablet hardness. Comparative Example 2 used single-layer compression, where citric acid and sodium bicarbonate were in close contact. Even with ethanol granulation, trace amounts of moisture or moisture absorbed during storage were sufficient to trigger an acid-base pre-reaction inside the granules, generating carbon dioxide and water. The moisture production further accelerated the reaction, creating a vicious cycle that weakened granule strength and loosened the internal structure, resulting in a "chaff-like" tablet with significantly increased brittleness. Comparative Example 3 used ordinary dextrin instead of β-cyclodextrin, which failed to achieve effective inclusion and stabilization, resulting in a loose granule structure, low tablet hardness, and increased brittleness.

[0060] 2. Effervescent and dissolving properties Pour 500 mL of water into a beaker and place it in a 40℃ constant temperature water bath. Take one tablet of the test sample and place it in the center of the beaker, while simultaneously starting a stopwatch. Effervescence time is defined as the time from when the tablet comes into contact with the water surface until it completely disintegrates without a solid core remaining. Record this time. Measure the pH value of the solution using a pH meter and record the reading. The results of the effervescence and dissolution characteristics test are shown in Table 2.

[0061] Table 2. Test data on effervescence and dissolution properties.

[0062] As shown in Table 2, compared with the comparative examples, the effervescence time of the tablets in Examples 1-4 was moderate (85.3s-104.1s), demonstrating the advantages of the double-layer compression structure. The physical separation of the drug bath layer and the effervescent layer controlled the reaction rate, resulting in stable and prolonged effervescence. The pH value of the solution was between 5.4 and 5.8, which is weakly acidic and close to the normal pH range of the skin, making it relatively mild. The solution was slightly turbid, which is due to the natural insoluble components in the medicinal materials and is a normal phenomenon. Comparative Example 1 did not use β-cyclodextrin inclusion, and the unencapsulated volatile oil could not dissolve in water and precipitated out. The extract and volatile oil hindered water penetration and acid-base reaction, resulting in slow tablet disintegration, the longest effervescence time, and a turbid solution with floating oil droplets. Comparative Example 2 had the shortest effervescence time. The single-layer tableting caused an acid-base reaction between citric acid and sodium bicarbonate, resulting in a poor user experience and potential safety hazards. Comparative Example 3 had a relatively long effervescence time, a turbid solution, and precipitation. This was because ordinary cyclodextrin was used, which could not effectively encapsulate the extract and volatile oil, resulting in poor solubility and dispersibility of the material, which affected water penetration and the effervescence reaction.

[0063] 3. Stability and retention rate of chemical components (1) Retention rate of volatile oil Add 300 mL of water, 10 g of effervescent tablet sample, and several boiling stones to the flask, and connect the volatile oil analyzer to the reflux condenser. Add water from the top of the condenser until it fills the graduated section of the volatile oil analyzer and overflows into the flask. Slowly heat to boiling and maintain a gentle boil for at least 5 hours, until the oil volume no longer increases. Stop heating and let stand for 2 hours until the oil layer is completely separated and clear. Open the stopcock at the bottom of the analyzer, and then open the stopcock again to allow the oil layer to drop until its top is level with the 0 mark on the scale. Read the volume of volatile oil. Volatile oil content (mL / g) = V / W, where V is the measured volume of volatile oil and W is the sample weight; Volatile oil retention rate (%) = (T... t (Content at time - content at time T0) × 100%, T t T0 represents the content in the third month, while T0 represents the initial content.

[0064] (2) Total flavonoid retention rate S1. Weigh the rutin reference standard dried to constant weight and add 60% ethanol to prepare a reference standard solution containing 0.2 mg per 1 mL.

[0065] S2. Weigh 1.0 g of the finely ground effervescent tablet sample and place it in a stoppered conical flask. Add 50 mL of 60% ethanol, seal tightly, and weigh. Sonicate (power 250W, frequency 40kHz) for 30 min, cool, weigh again, replenish the lost weight with 60% ethanol, shake well, filter, and use the filtrate as the test solution.

[0066] S3. Measure 0.5, 1.0, 2.0, 3.0, and 4.0 mL of the reference solution and place them in separate 10 mL volumetric flasks. Add 30% ethanol to each flask to a final volume of 5 mL. First, add 0.3 mL of 5% sodium nitrite solution, shake well, and let stand for 6 min. Then, add 0.3 mL of 10% aluminum nitrate solution, shake well, and let stand for 6 min. Finally, add 4 mL of 4% sodium hydroxide solution, then add 30% ethanol to the mark, shake well, and let stand for 15 min.

[0067] S4. Using the first tube (0.5 mL of reference standard) as a blank, measure the absorbance at a wavelength of 510 nm. Plot a standard curve with absorbance on the ordinate and concentration on the abscissa.

[0068] S5. Accurately measure 1 mL of the test solution and place it in a 10 mL volumetric flask. Following the method under "Standard Curve Plotting," starting from "Add 30% ethanol to 5 mL," proceed as instructed and determine the absorbance. Read the concentration (C, mg / mL) of total flavonoids in the test solution from the standard curve.

[0069] S6. Total flavonoid content (mg / g) = (C×V) / W, where C is the concentration obtained from the standard curve (mg / mL), V is the volume of the test solution (50 mL here), and W is the sample weight (g); Total flavonoid retention rate (%) = (T t (Content at time - content at time T0) × 100%, T t The content is shown in Table 3, where T0 is the initial content and T3 is the content at month 3. The results of the chemical composition stability and retention rate tests are shown in Table 3.

[0070] Table 3. Test data on the stability and retention rate of chemical components.

[0071] As shown in Table 3, the effervescent tablets prepared in Examples 1-4 retained more than 91% of their volatile oils and more than 94% of their total flavonoids after 3 months, indicating that the microencapsulation technology of β-cyclodextrin prevented the volatilization of volatile oils and the degradation of flavonoids. In contrast, Comparative Examples 1 and 3 lacked effective encapsulation protection, resulting in rapid loss of active ingredients under high temperature and humidity conditions, shortened product shelf life, and reduced efficacy. Comparative Example 2, due to its single-layer compression method, underwent a pre-reaction during preparation, leading to significant degradation of the initial components; therefore, no component stability test was performed.

[0072] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A Tibetan medicinal bath effervescent composition, characterized in that, The composition comprises the following components by weight: 30-60 parts of β-cyclodextrin microencapsulated inclusion compound of Wumei Ganlu Decoction, 15-35 parts of citric acid, 20-40 parts of a first diluent, 1-3 parts of a first lubricant, 25-50 parts of sodium bicarbonate, 20-45 parts of a second diluent, and 1-3 parts of a second lubricant; the composition comprises a medicated layer and an effervescent layer.

2. A method for preparing a Tibetan medicine bath effervescent composition, wherein the Tibetan medicine bath effervescent composition is as described in claim 1, characterized in that, The method comprises the following steps: Step 1: weighing Wumei Ganlu Decoction crude medicinal materials, extracting volatile oil, and obtaining total extract after alcohol precipitation of water extract; dissolving β-cyclodextrin in water, adding the mixture of volatile oil and total extract for inclusion reaction, filtering and drying after cooling to obtain β-cyclodextrin microencapsulated inclusion compound of Wumei Ganlu Decoction; Step 2: mixing β-cyclodextrin microencapsulated inclusion compound of Wumei Ganlu Decoction, citric acid, and a first diluent, preparing soft material with pure water as a binder, sieving and granulating, and drying to obtain medicated layer granules; Step 3: mixing sodium bicarbonate and a second diluent, preparing soft material with ethanol as a binder, sieving and granulating, and drying to obtain effervescent layer granules; Step 4: mixing medicated layer granules and a first lubricant, mixing effervescent layer granules and a second lubricant, filling the two layers of materials in sequence using a double-layer tablet press, and tabletting to obtain a Tibetan medicated bath effervescent composition.

3. The method for preparing a Tibetan medicine bath effervescent composition according to claim 2, characterized in that, The components by weight of Wumei Ganlu Decoction crude medicinal materials in step 1 are: 20-40 parts of Ledum palustre, 15-30 parts of Artemisia japonica, 20-40 parts of Ephedra przewalskii, 20-40 parts of Myricaria nutans, and 20-40 parts of Artemisia indica.

4. The method for preparing a Tibetan medicine bath effervescent composition according to claim 2, characterized in that, The temperature of the inclusion reaction in step 1 is 40-60°C, and the time is 1-3 hours.

5. The method for preparing a Tibetan medicine bath effervescent composition according to claim 2, characterized in that, The drying temperature in steps 2 and 3 is 40-60°C, and the water content of the granules after drying is 1.0-2.5%.

6. The method for preparing a Tibetan medicine bath effervescent composition according to claim 2, characterized in that, Both the first diluent and the second diluent are mannitol.

7. The method for preparing a Tibetan medicine bath effervescent composition according to claim 2, characterized in that, Both the first lubricant and the second lubricant are polyethylene glycol 6000.

8. The method for preparing a Tibetan medicine bath effervescent composition according to claim 2, characterized in that, The mass ratio of medicated layer granules, the first lubricant, effervescent layer granules, and the first lubricant in step 4 is 10: (0.05-0.1). 10：（0.05-0.1）。 9. The method for preparing a Tibetan medicine bath effervescent composition according to claim 2, characterized in that, The hardness of the tablet in step 4 is 70-120 N, and the tablet weight is 3-8 g.

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