Method for preparing a transdermal patch and formulations related thereto

Abstract

The application relates to a preparation method of a Gan Tong Pian and a related preparation and belongs to the field of traditional Chinese medicine preparations. The preparation method comprises the following steps: 1) extracting volatile oil from honeysuckle by adding 10 times the amount of water; collecting the water solution after distillation; 2) taking isatis root, soaking the isatis root in a solvent at room temperature, filtering the isatis root after soaking, drying the isatis root after soaking, and crushing the isatis root into fine powder for standby; 3) combining the remaining isatis root with gardenia, licorice and indigowood, adding water to the combination to boil three times, filtering the combination, combining the filtrate with the above water solution, filtering the combination, adding ethanol to the filtrate until the ethanol content is 60%, filtering the combination, recovering ethanol from the filtrate, and concentrating the filtrate into thick paste; 4) mixing the thick paste with the above fine powder, drying the mixture, crushing the mixture into fine powder, mixing the fine powder with paracetamol, amantadine hydrochloride and appropriate accessories, uniformly mixing the mixture, preparing granules, spraying the volatile oil into the granules, uniformly mixing the granules, pressing the granules, coating the granules with film, and obtaining the Gan Tong Pian.

Description

Technical Field

[0001] This invention relates to a method for preparing Gantong tablets and related formulations, belonging to the field of traditional Chinese medicine preparations. Background Technology

[0002] Gantong tablets are a combination of traditional Chinese and Western medicine for treating colds. They are composed of Chinese medicine ingredients and Western medicine ingredients and have the effects of clearing heat and detoxifying, dispelling wind and relieving exterior symptoms, relieving fever and pain, and antiviral effects. They are suitable for the treatment of colds with wind-heat syndrome.

[0003] The existing preparation method is as follows: 185.2g of honeysuckle, 92.6g of gardenia, 111.1g of isatis root, 37g of licorice, 111.1g of indigo leaf, 125g of acetaminophen, and 50g of amantadine hydrochloride; For these seven ingredients, add 10 times the amount of water to honeysuckle and extract the volatile oil for 6 hours. Collect the distilled aqueous solution separately. Separately, 25g of isatis root is pulverized into a fine powder and set aside. The remaining isatis root is combined with gardenia, licorice, and indigo leaf, and decocted three times with 8 times the amount of water each time, for 1.5 minutes each time. After 24 hours, combine the decoctions, filter, combine the filtrate with the above aqueous solution, filter again, concentrate the filtrate to a relative density of 1.13-1.15 (60℃), add ethanol to a content of 60%, let stand for 24 hours, filter, recover the ethanol from the filtrate, and concentrate to a thick paste with a relative density of 1.30-1.35 (60℃), mix with the above fine powder, dry, pulverize into fine powder, mix with acetaminophen, amantadine hydrochloride and appropriate excipients, granulate, spray in the above volatile oil, mix, compress into 1000 tablets, coat with film, and the product is obtained.

[0004] Gantong tablets are a novel compound preparation developed under the guidance of traditional Chinese medicine theory and modern medical technology, through years of clinical practice and scientific verification. It combines the advantages of both traditional Chinese medicine and Western medicine, leveraging the holistic regulation and syndrome differentiation-based treatment characteristics of traditional Chinese medicine while utilizing the rapid onset and targeted effects of Western medicine. Gantong tablets not only relieve various uncomfortable symptoms caused by the cold but also enhance the body's immunity, prevent complications and recurrence, and improve the quality of recovery.

[0005] However, in modern clinical applications, there are occasional reports of kidney damage in patients taking Gan Tong Pian (a traditional Chinese medicine), raising concerns about its safety. Based on current literature, the acetaminophen component in Gan Tong Pian has a certain nephrotoxic effect, but the reasons for this effect are not reported in the literature. Therefore, providing a Gan Tong Pian with better safety while maintaining its active ingredients is innovative and practically valuable, offering a safe, effective, comprehensive, and widely applicable treatment option for a wide range of cold sufferers. Summary of the Invention

[0006] A first aspect of the present invention is to provide a method for preparing a sensor sheet, comprising:

[0007] Prescription composition: Honeysuckle 185.2g, Gardenia 92.6g, Isatis root 111.1g, Licorice 37g, Isatis leaf 111.1g, Acetaminophen 125g and Amantadine hydrochloride 50g;

[0008] 1) Add 10 times the amount of water to honeysuckle to extract the volatile oil; collect the distilled aqueous solution separately.

[0009] 2) Take 25g of Isatis root, soak it in a solvent at room temperature, filter it after soaking, dry the soaked medicinal material and grind it into fine powder for later use;

[0010] 3) Combine the remaining Isatis root with Gardenia, Licorice, and Isatis leaf, add water and decoct three times, adding 8 times the amount of water each time, decoct for 1.5 hours each time, combine the decoctions, filter, combine the filtrate with the above aqueous solution, filter, concentrate the filtrate to a relative density of 1.13-1.15 (60℃), add ethanol to a concentration of 60%, let stand for 24 hours, filter, recover the ethanol from the filtrate, and concentrate to a thick paste with a relative density of 1.30-1.35 (60℃);

[0011] 4) Mix the thick paste with the above fine powder, dry it, pulverize it into fine powder, mix it with acetaminophen, amantadine hydrochloride and appropriate excipients, make it into granules, spray in the above volatile oil, mix it, press it into 1000 tablets, and coat it with a film to obtain the final product.

[0012] In one embodiment, in step 2), the solvent is selected from one or more of ethyl acetate, a 15% (volume) aqueous acetic acid solution, and / or a 60% ethanol solution. In a further embodiment, the solvent is a combination of a 15% (volume) aqueous acetic acid solution and a 60% ethanol solution. In an even further embodiment, the volume ratio of the 15% (volume) aqueous acetic acid solution to the 60% ethanol solution is 1:0.25-4, preferably 1:1-2.

[0013] In another embodiment, in step 2), the Isatis root is treated with 1-4 times the amount of solvent; preferably, 2 times the amount of solvent is used to treat the Isatis root.

[0014] In another implementation, the room temperature soaking time in step 2) is 4 hours.

[0015] A second aspect of the present invention is to provide a sensor sheet product prepared by the said preparation method.

[0016] A third aspect of the present invention is to provide the use of the aforementioned sensory tablet in the preparation of medicines for treating colds and fevers.

[0017] Through experimental screening, this invention discovered that the raw material of Isatis indigotica and acetaminophen in the various components of Gantong tablets produced a synergistic toxic effect on renal cells. Based on the mechanism, it is speculated that this may be related to certain chemical components in the raw material of Isatis indigotica promoting the absorption of acetaminophen by renal cells. Furthermore, this invention investigated the pretreatment of the raw material of Isatis indigotica and discovered a treatment process that can weaken this effect. Unexpectedly, it was found that this treatment process not only reduced the nephrotoxicity of Gantong tablets but also improved the antipyretic effect of Gantong tablets. Detailed Implementation

[0018] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0019] Example 1: Toxicity study of the active ingredient in GanTong tablets on human kidney cells (HEK293).

[0020] (I) Based on the results of previous literature review and the preparation method of Gantong tablets, this invention divides Gantong tablets into the following active components for human renal cell toxicity investigation, as follows:

[0021] The prescription for Gantong tablets is as follows: honeysuckle 185.2g, gardenia 92.6g, isatis root 111.1g, licorice 37g, indigo leaf 111.1g, acetaminophen 125g, and amantadine hydrochloride 50g.

[0022] Component 1) Honeysuckle volatile oil: Take 18.52g of honeysuckle, add 10 times the amount of water, extract the volatile oil, and extract for 6 hours to obtain 15.6mg of volatile oil.

[0023] Component 2) Aqueous extract: The aqueous solution after distillation of honeysuckle was collected separately; 8.61g of Isatis root, 9.26g of gardenia, 3.7g of licorice, and 11.11g of Isatis leaf were combined and decocted three times with water, each time adding 8 times the amount of water, for 1.5 hours. The decoctions were combined and filtered. The filtrate was combined with the above aqueous solution and filtered again. The filtrate was concentrated to a relative density of 1.13-1.15 (60℃), and ethanol was added to a concentration of 60%. The mixture was allowed to stand for 24 hours, filtered, and the ethanol was recovered from the filtrate. The filtrate was then concentrated to a thick paste with a relative density of 1.30-1.35 (60℃), dried, and 5.37g of aqueous extract was obtained.

[0024] Component 3) Isatis root raw material: Take 2.5g of Isatis root, crush it into fine powder, extract it with 4 times the amount of water at 37℃ for 12h, filter it, recover the solvent from the filtrate, and dry it to obtain 0.13g of Isatis root raw material extract.

[0025] Component 4) Acetaminophen 12.5g.

[0026] Component 5) Amantadine 5g.

[0027] (II) Cell Culture: HEK293 cells were used to prepare a cell suspension in MEM medium containing 10% FBS, with a concentration of 5 × 10⁻⁶ cells / mL. 4 Cells were cultured at a density of 200 μl / ml in 96-well plates, and incubated in a 5% CO2 incubator at 37°C. The medium was changed every 24 hours. After 3 days of culture, relevant tests were performed.

[0028] (III) Detection method: The above components 1-5 or combinations thereof were prepared into solutions of different concentrations using MEM medium, and then added to 96-well plates containing HEK293 cells (the control group was added with an equal amount of MEM medium). Each group had 6 replicates. After incubation for 24 hours, cell viability was measured by the MTT assay. The cell viability rate of each group was calculated as: absorbance of the drug group / absorbance of the control group × 100%.

[0029] (iv) Grouping and Results:

[0030] 1) The single component of the sensory tablet has an IC50 effect on HEK293 cells. 50 The median lethal concentration (IC50) was determined by preparing solutions of components 1-5 at different concentrations, calculating the cell viability of each group, and then calculating the IC50 value for each component. 50 The values ​​are as follows:

[0031] Component 1 >100mg / ml Component 2 58.42 mg / ml Component 3 14.57mg / ml Component 4 0.51mg / ml Component 5 >100mg / ml

[0032] To evaluate the nephrotoxicity of Isatis root raw material in Gantong tablets, this invention used simulated in vivo temperature to extract Isatis root and then conducted nephrotoxicity tests. The results show that honeysuckle volatile oil and amantadine have relatively weak toxicity to renal cells; while water extract component 2 containing Isatis root and Daqing leaf, component 3 of Isatis root raw material, and component 4 of acetaminophen all have significant toxicity to renal cells, with component 4 being the most toxic.

[0033] 2) Based on the above results, in order to further investigate the cause of the nephrotoxicity of Gantong tablets, the present invention conducted IC50 assay using a mixture of components. 50 The testing method is the same as above. The mixing weight ratio of each component shall strictly follow the weight ratio of the extract or raw material obtained from each component in Part (I). The specific grouping is as follows:

[0034] Group 1: Component 1 (15.6 mg) + Component 2 (5.37 g) + Component 3 (0.13 g) + Component 4 (12.5 g) + Component 5 (5 g)

[0035] Group 2: Component 2 (5.37g) + Component 4 (12.5g)

[0036] Group 3: Component 3 (0.13g) + Component 4 (12.5g)

[0037] ICs in each group 50 The values ​​are shown in the table below:

[0038] Group 1 8.77mg / ml Group 2 0.45mg / ml Group 3 0.07mg / ml

[0039] The results show that when the nephrotoxicity of the whole active component of Gantong tablets (i.e., group 1) was investigated, its toxicity was significantly reduced compared with the acetaminophen group, but the toxicity was still relatively strong; the nephrotoxicity of the mixed group of water-soluble extract and acetaminophen was not much different from that of the acetaminophen alone group; and the toxicity of the mixed group of Banlangen raw material and acetaminophen was significantly higher than that of the acetaminophen alone group. This suggests that the Banlangen raw material group may have a synergistic effect with the acetaminophen group in terms of nephrotoxicity, which will be the key to improving the nephrotoxicity of Gantong tablets.

[0040] Example 2: Effects of different processing methods on nephrotoxicity of Isatis indigotica raw material

[0041] The raw material of Isatis indigotica was pretreated without solvent, and then processed according to the method of component 3 in Example 1. The obtained extract was mixed with the acetaminophen group of component 4 in Example 1 according to the weight ratio, and the IC50 of each group was tested according to the method of Example 1. 50 value.

[0042] Petroleum ether group: The raw material of Isatis indigotica was soaked in 2 times the amount of petroleum ether for 4 hours, then filtered and the solvent was discarded. The raw material was dried to evaporate the solvent, and then extracted with 4 times the amount of water at 37°C for 12 hours. After filtration, the solvent was recovered from the filtrate and dried to obtain the raw material of Isatis indigotica. Then it was mixed with component 4, acetaminophen, according to the proportion principle of Example 1, and diluted with culture medium to obtain multiple concentrations.

[0043] Ethyl acetate group: Replace petroleum ether with an equal volume of ethyl acetate, and other treatment methods are the same as for the petroleum ether group.

[0044] 15% (by weight) alum aqueous solution group: Replace petroleum ether with an equal volume of 15% (by weight) alum aqueous solution, and other treatment methods are the same as those for the petroleum ether group.

[0045] 15% (volume) acetic acid aqueous solution group: Replace petroleum ether with an equal volume of 15% (volume) acetic acid aqueous solution group, and other treatment methods are the same as petroleum ether group.

[0046] 60% ethanol group: Replace petroleum ether with an equal volume of 60% ethanol group, and other treatment methods are the same as petroleum ether group.

[0047] 1) IC50 of each group on HEK293 cells 50 The values ​​are shown in the table below:

[0048] Petroleum ether group 0.05mg / ml Ethyl acetate group 0.19mg / ml 15% (by weight) alum aqueous solution group 0.09mg / ml 15% (volume) acetic acid aqueous solution group 0.31mg / ml 60% ethanol solution group 0.28mg / ml

[0049] The results show that the nephrotoxicity of Isatis indigotica mixed with acetaminophen was further aggravated after treatment with petroleum ether, the alum aqueous solution treatment had little effect on nephrotoxicity, and the nephrotoxicity of the acetic acid aqueous solution treatment group and the ethanol treatment group was significantly improved.

[0050] 2) Treatment of HEK293 cells with mixed solvents to reduce IC50 50 The influence of value

[0051] 15% (volume) aqueous acetic acid and 60% ethanol were mixed at different volume ratios, and then the raw material of Isatis indigotica was treated according to the above method. The IC50 of each group was then determined. 50 The values ​​are shown in the table below:

[0052]

[0053]

[0054] The above results indicate that the mixed toxicity of the treated Isatis indigotica raw material and acetaminophen is lowest when the volume ratio of 15% (volume) aqueous acetic acid and 60% ethanol is 1:2 or 1:1.

[0055] 3) HEK293 cell IC50 containing the complete component group of the induction tablet treated with mixed solvent 50 value

[0056] The raw material of Isatis indigotica was treated with a volume ratio of 15% (volume) acetic acid aqueous solution and 60% ethanol of 1:2 or 1:1 as described in 2). Then, components 1-5 were mixed according to the weight ratio principle of Example 1, and dissolved in MEM medium. The IC50 of HEK293 cells was determined according to the method of Example 1. 50 The values ​​and results are as follows:

[0057]

[0058] The results in the table above indicate that the nephrotoxicity of the entire Gantong tablet was significantly reduced after the synergistic nephrotoxicity of Isatis root and acetaminophen was improved.

[0059] Example 3: Effect of the new preparation process on the heat dissipation effect of the induction plate

[0060] One hundred SPF-grade SD rats, weighing approximately 200g, with half males and half females, were used and housed under standard photoperiod conditions. They were randomly assigned to groups. Rectal temperature was measured in each rat three times prior to modeling, and this was used as the basal body temperature. Specific grouping and drug dosages are as follows;

[0061] 1) Blank control group: Administered an equal volume of normal saline via gavage;

[0062] 2) Model group: Administered an equal volume of physiological saline via gavage;

[0063] 3) Group 1: The active ingredient of Yuan Gan Tong tablets was administered by gavage at a dose of 100 mg / kg. The preparation method was as follows: 185.2 g of honeysuckle, 92.6 g of gardenia, 111.1 g of isatis root, 37 g of licorice, 111.1 g of indigo leaf, 125 g of acetaminophen, and 50 g of amantadine hydrochloride. For the above seven ingredients, honeysuckle was mixed with 10 times the amount of water, and the volatile oil was extracted for 6 hours. The distilled aqueous solution was collected separately. 25 g of isatis root was crushed into a fine powder for later use. The remaining isatis root was combined with gardenia, licorice, and indigo leaf, and decocted with water. Three times, each time adding 8 times the amount of water, decocting for 1.5 hours, combining the decoctions, filtering, combining the filtrate with the above aqueous solution, filtering, concentrating the filtrate to a relative density of 1.13-1.15 (60℃), adding ethanol to a 60% alcohol content, letting stand for 24 hours, filtering, recovering the ethanol from the filtrate, and concentrating to a thick paste with a relative density of 1.30-1.35 (60℃), mixing with the above fine powder, drying, pulverizing into a fine powder, mixing with acetaminophen and amantadine hydrochloride, making granules, spraying with volatile oil to obtain the final product; then administering it as a suspension in 1% CMC-Na physiological saline.

[0064] 4) Group 2: The active ingredient of the new process GanTong tablets was administered by gavage at a dose of 100 mg / kg. The preparation method is as follows:

[0065] Honeysuckle 185.2g, Gardenia 92.6g, Isatis root 111.1g, Licorice 37g, Isatis leaf 111.1g, Acetaminophen 125g, and Amantadine hydrochloride 50g; Take the above seven ingredients, add 10 times the amount of water to honeysuckle, extract the volatile oil for 6 hours, and collect the distilled aqueous solution separately;

[0066] Take another 25g of Isatis root, soak it in twice the amount of 15% (volume) acetic acid aqueous solution and 60% ethanol solution (volume ratio of the two is 1:2) at room temperature for 4 hours, filter and discard the solvent, dry the medicinal material to evaporate the solvent, and then pulverize it into fine powder for later use;

[0067] The remaining Isatis root, gardenia, licorice, and indigo leaves were combined and decocted three times with water, each time adding 8 times the amount of water and decocting for 1.5 hours. The decoctions were combined and filtered. The filtrate was combined with the above aqueous solution and filtered again. The filtrate was concentrated to a relative density of 1.13-1.15 (60℃), and ethanol was added to a concentration of 60%. The mixture was allowed to stand for 24 hours, filtered, and the ethanol was recovered from the filtrate. The filtrate was then concentrated to a thick paste with a relative density of 1.30-1.35 (60℃). This paste was mixed with the above fine powder, dried, and pulverized into a fine powder. The powder was then mixed with acetaminophen, amantadine hydrochloride, and appropriate excipients to form granules. The volatile oil was sprayed into the granules, mixed, and then administered as a suspension in 1% CMC-Na physiological saline.

[0068] 5) Group 3: The active ingredient of the new process GanTong tablets was administered by gavage at a dose of 100 mg / kg. The preparation method is as follows:

[0069] Honeysuckle 185.2g, Gardenia 92.6g, Isatis root 111.1g, Licorice 37g, Isatis leaf 111.1g, Acetaminophen 125g, and Amantadine hydrochloride 50g; Take the above seven ingredients, add 10 times the amount of water to honeysuckle, extract the volatile oil for 6 hours, and collect the distilled aqueous solution separately;

[0070] Take another 25g of Isatis root, soak it in twice the amount of 15% (volume) acetic acid aqueous solution and 60% ethanol solution (volume ratio of the two is 1:1) at room temperature for 4 hours, filter and discard the solvent, dry the medicinal material to evaporate the solvent, and then pulverize it into fine powder for later use;

[0071] The remaining Isatis root, gardenia, licorice, and indigo leaves were combined and decocted three times with water, each time adding 8 times the amount of water and decocting for 1.5 hours. The decoctions were combined and filtered. The filtrate was combined with the above aqueous solution and filtered again. The filtrate was concentrated to a relative density of 1.13-1.15 (60℃), and ethanol was added to a concentration of 60%. The mixture was allowed to stand for 24 hours, filtered, and the ethanol was recovered from the filtrate. The filtrate was then concentrated to a thick paste with a relative density of 1.30-1.35 (60℃). This paste was mixed with the above fine powder, dried, and pulverized into a fine powder. The powder was then mixed with acetaminophen, amantadine hydrochloride, and appropriate excipients to form granules. The volatile oil was sprayed into the granules, mixed, and then administered as a suspension in 1% CMC-Na physiological saline.

[0072] After grouping, except for the blank control group, rats in the other groups were subcutaneously injected with 20% dry yeast suspension in their backs at a dose of 10 ml / kg. Six hours after modeling, rats with a body temperature increase of 0.8℃ were selected as model animals, and each group of animals was then administered the drug once. The rectal temperature of rats in each group was measured at 4 and 8 hours after drug administration, and the temperature difference (Δt = real-time body temperature - basal body temperature) was calculated. SPSS 20.0 software was used to analyze the data of each group.

[0073] The results are as follows:

[0074] Blank control group -0.42±0.11 0.14±0.06 Model group 1.27±0.22 2.38±0.29 Group 1 <![CDATA[0.73±0.14 a ]]> <![CDATA[0.94±0.18 a ]]> Group 2 <![CDATA[0.51±0.09 a ]]> <![CDATA[0.63±0.15 a ]]> Group 3 <![CDATA[0.78±0.16 a ]]> <![CDATA[1.02±0.21 a ]]>

[0075] 'a' represents the result compared to the model group; according to the Oneway-ANOVA test, p < 0.01.

[0076] To examine the efficacy of the modified Gantong tablets, the antipyretic effect, a key therapeutic function of Gantong tablets, was used as the evaluation index. The results showed that although both process improvement groups (drug groups 2 and 3) exhibited significant reductions in nephrotoxicity, effectively mitigating the risk of acute nephrotoxicity from acetaminophen in clinical practice, the activity of Gantong tablets needed to be re-evaluated. After all, treatment with acetic acid and ethanol solutions may lead to the loss of active ingredients in Isatis indigotica root. In this study, drug group 2 was found to be significantly superior to the original formulation group (drug group 1) and drug group 3 in terms of antipyretic effect. Therefore, considering both toxicity reduction and activity evaluation, the preferred method for processing Isatis indigotica root raw materials is soaking in twice the volume of 15% (volume) acetic acid aqueous solution and 60% ethanol solution (volume ratio 1:2) at room temperature for 4 hours.

[0077] Example 4: Preparation of the Sensing Sheet

[0078] Honeysuckle 185.2g, Gardenia 92.6g, Isatis root 111.1g, Licorice 37g, Isatis leaf 111.1g, Acetaminophen 125g, and Amantadine hydrochloride 50g; the above seven ingredients,

[0079] Take honeysuckle, add 10 times the amount of water, extract the volatile oil, and extract for 6 hours. Collect the distilled aqueous solution separately.

[0080] Take another 25g of Isatis root, soak it in twice the amount of 15% (volume) acetic acid aqueous solution and 60% ethanol solution (volume ratio of the two is 1:2) at room temperature for 4 hours, filter and discard the solvent, dry the medicinal material to evaporate the solvent, and then pulverize it into fine powder for later use;

[0081] The remaining Isatis root, gardenia, licorice, and indigo leaves are combined and decocted three times with water, each time adding 8 times the amount of water, for 1.5 hours. The decoctions are combined and filtered. The filtrate is combined with the above aqueous solution and filtered again. The filtrate is concentrated to a relative density of 1.13-1.15 (60℃), and ethanol is added to a concentration of 60%. The mixture is allowed to stand for 24 hours, filtered, and the ethanol is recovered from the filtrate. The filtrate is then concentrated to a thick paste with a relative density of 1.30-1.35 (60℃). This paste is mixed with the above fine powder, dried, and pulverized into a fine powder. It is then mixed with acetaminophen, amantadine hydrochloride, and an appropriate amount of starch to form granules. The volatile oil is sprayed into the granules, mixed, and pressed into 1000 tablets. The tablets are then coated with a thin film to obtain the final product.

Claims

1. A method for preparing a sensor sheet, comprising: Prescription composition: Honeysuckle 185.2g, Gardenia 92.6g, Isatis root 111.1g, Licorice 37g, Isatis leaf 111.1g, Acetaminophen 125g and Amantadine hydrochloride 50g; 1) Add 10 times the amount of water to honeysuckle to extract the volatile oil; collect the distilled aqueous solution separately. 2) Take 25g of Isatis root, soak it in 1-4 times the amount of solvent at room temperature, filter it after soaking, dry the soaked medicinal material and grind it into fine powder for later use; the solvent is composed of 15% acetic acid aqueous solution and 60% ethanol solution; the volume ratio of 15% acetic acid aqueous solution to 60% ethanol solution is 1:

2. 3) Combine the remaining Isatis root with Gardenia, Licorice, and Isatis leaf, add water and decoct three times, adding 8 times the amount of water each time, decoct for 1.5 hours each time, combine the decoctions, filter, combine the filtrate with the aqueous solution in step 1 above, filter, concentrate the filtrate to a relative density of 1.13-1.15 at 60℃, add ethanol to a concentration of 60%, let stand for 24 hours, filter, recover the ethanol from the filtrate, and concentrate to a thick paste with a relative density of 1.30-1.35 at 60℃; 4) Mix the thick paste with the above fine powder, dry it, pulverize it into fine powder, mix it with acetaminophen, amantadine hydrochloride and appropriate excipients, make it into granules, spray in the above volatile oil, mix it, press it into 1000 tablets, and coat it with a film to obtain the final product.

2. The preparation method according to claim 1, characterized in that, In step 2), the Isatis root is treated with twice the amount of solvent.

3. The preparation method according to claim 1, characterized in that, The soaking time at room temperature in step 2) is 4 hours.

4. The sensor sheet product prepared by the preparation method according to any one of claims 1-3.

5. The use of the Gantong tablet as described in claim 4 in the preparation of medicines for treating colds and fever.

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