Traditional Chinese medicine granules and preparation method thereof

Abstract

The invention relates to the field of traditional Chinese medicine preparations, and particularly provides traditional Chinese medicine granules and a preparation method thereof.The preparation method comprises the steps that lauryl sodium sulfate, stearic acid, Eudragit EPO and water are mixed to prepare an aqueous dispersion, the pH value of a traditional Chinese medicine extraction concentrated solution is adjusted to 7.5-10, the aqueous dispersion and the pH-value-adjusted traditional Chinese medicine extraction concentrated solution are heated to 50-70 DEG C and then mixed, and the traditional Chinese medicine granules are prepared. The method has the advantages that the taste masking effect is good, the dosage of the auxiliary materials is small, the preparation process is simple, the bitterness of the medicine can be effectively masked, the medicine can be uniformly dispersed in water, foreign body sensation cannot be generated when the medicine is taken by a patient, and meanwhile, the release and absorption of the medicine are not influenced.

Description

Technical Field

[0001] The present invention relates to the field of Chinese medicine preparations, and in particular to Chinese medicine granules and a preparation method thereof. Background Art

[0002] Chinese medicine granules are granules for clinical prescriptions of traditional Chinese medicine, which are prepared from single or multiple Chinese medicine slices according to traditional standards, and then extracted, concentrated, dried, etc. It is a new type of prescription medicine with unified specifications, unified dosage and unified quality standards, which is made from traditional Chinese medicine slices through production processes such as extraction, separation, concentration, drying, granulation and packaging. It is recognized and accepted by clinical patients and doctors for its stable quality, accurate dosage, convenient administration, safety and hygiene.

[0003] However, due to the high drug concentration and poor taste of Chinese herbal granules, they often have unpleasant tastes such as bitterness, astringency, and sourness, which cause taste discomfort or even vomiting in patients when using them. Children in particular have poor compliance, and treatment is often delayed because children refuse to cooperate with the medication, which limits their use in pediatric patients. Therefore, it is necessary to conduct research on the taste correction of Chinese herbal granules to improve patient compliance.

[0004] At present, the commonly used methods for drug flavor correction include film coating technology, molecular inclusion technology, resin adsorption technology, wax material coating technology, emulsion coating technology, effervescent technology, and the simple use of sweeteners or edible flavors. Among them, molecular inclusion technology is to encapsulate the drug in the cavity of the main molecule such as cyclodextrin, which can reduce the contact between the drug and the taste buds and achieve the purpose of flavor correction. However, due to the large amount of cyclodextrin and other substances used in molecular inclusion technology, the ratio with the drug is usually above 1:1, so it is not suitable for the flavor correction of Chinese medicine granules. Resin adsorption technology has been less studied in China, and there are also fewer ion exchange resin materials that can be used for medicinal purposes. The preparation process is complicated and the cost is high. Wax material coating technology, emulsion coating technology, and effervescent technology are complex and have high operating requirements. The simple use of sweeteners or edible flavors has limited flavor correction effects, and the simple use of a certain sweetener or edible flavor cannot achieve a good taste masking effect. Film coating technology is often used to mask the taste of tablets. However, for Chinese herbal granules that need to be taken with hot water, the effect of the solubility of the granules on the taste must be considered. Therefore, conventional film coating is not suitable for masking the taste of Chinese herbal granules.

[0005] In addition, organic solvents are not allowed to be used in the preparation process of Chinese herbal granules. Therefore, there is an urgent need for a preparation method for Chinese herbal granules that uses a small amount of auxiliary materials, has a simple preparation process, has a good taste-masking effect, and does not use organic solvents. Summary of the invention

[0006] Therefore, the object of the present invention is to provide a method for preparing Chinese medicine granules which has a small amount of auxiliary materials, a simple preparation process, good taste-masking effect, and does not use organic solvents.

[0007] To this end, the present invention provides a method for preparing Chinese medicine granules, comprising the following steps:

[0008] Preparation of aqueous dispersion: Sodium lauryl sulfate, stearic acid, Eudragit EPO and water are mixed to prepare aqueous dispersion;

[0009] Preparation of Chinese medicine granules: adjust the pH value of the Chinese medicine extract concentrate to 7.5-10 with an alkaline solution, heat the water dispersion and the Chinese medicine extract concentrate after the pH value is adjusted to 50-70°C respectively and then mix them, dry them, add or not add auxiliary materials, and granulate them to obtain Chinese medicine granules.

[0010] In the present invention, the Chinese medicine granules can be compound granules or Chinese medicine formula granules.

[0011] In the present invention, the term Chinese medicine extract concentrate refers to a concentrate prepared from Chinese medicinal materials or Chinese medicinal pieces according to conventional methods in the art. For example, the Chinese medicinal pieces are boiled in water, filtered, and the filtrate is concentrated. The number of decoctions is at least 1 time (e.g., 1-3 times), and water is added at least 2 times (e.g., 5-20 times) of the amount of the medicinal pieces each time, and the decoction time is at least 1 hour (e.g., 1-3 hours).

[0012] Furthermore, the mass ratio of Eudragit EPO, sodium lauryl sulfate and stearic acid is 60-80:10-20:10-20.

[0013] Furthermore, in the aqueous dispersion, the mass percentage of Eudragit EPO to the mass of water is 5-10%.

[0014] Furthermore, in the process of preparing the aqueous dispersion, sodium lauryl sulfate, stearic acid and Eudragit® EPO are added to water while stirring, and stirring is continued for more than 1 hour (eg, 1 hour or 2 hours) after the addition.

[0015] Furthermore, the Chinese medicine extract concentrate further comprises a step of adding water to dilute the concentrate to a relative density of 1.04-1.1 at 50-70° C. before adjusting the pH value.

[0016] In the preparation process of the Chinese medicine granules, an alkaline solution is used to adjust the pH value of the Chinese medicine extract concentrate;

[0017] Preferably, the alkaline solution is selected from one or more of NaOH solution, Na2CO3 solution, KOH solution, and NaHCO3 solution;

[0018] Preferably, the mass concentration of the alkaline solution is 1-5%.

[0019] Furthermore, the granulation is dry granulation; and / or the Chinese medicine extract concentrate is selected from at least one of Houttuynia cordata extract concentrate, Pheretima extract concentrate, and Lotus leaf extract concentrate.

[0020] Furthermore, the auxiliary material is one or more of dextrin, lactose, and maltodextrin; the preferred auxiliary material is maltodextrin; preferably, the ratio of the mass of dry matter in the Chinese medicine extract concentrate to the mass of the auxiliary material is 180-250:40.

[0021] Furthermore, during the preparation of the Chinese medicine granules, the ratio of the mass of dry matter in the Chinese medicine extract concentrate to the total mass of sodium dodecyl sulfate, stearic acid and Eudragit® EPO in the aqueous dispersion is 1.2:1 to 2:1.

[0022] Adding more than 2 times the amount of water to the medicinal pieces means that the mass of the added water is more than twice the mass of the medicinal pieces.

[0023] Furthermore, the method further includes the step of sieving and taking the sieve material before drying.

[0024] Furthermore, the drying is spray drying. Preferably, the inlet air temperature of the spray drying is 140-170°C, and the outlet air temperature is maintained at 75-90°C.

[0025] The present invention also provides Chinese medicine granules prepared by any of the above-mentioned preparation methods. Preferably, the Chinese medicine granules are selected from at least one of Houttuynia cordata formula granules, Pheretima formula granules, and Lotus leaf formula granules.

[0026] The technical solution of the present invention has the following advantages:

[0027] 1. The preparation method of the traditional Chinese medicine granules provided by the present invention comprises the following steps: mixing sodium dodecyl sulfate, stearic acid, Eudragit® EPO and water to prepare an aqueous dispersion, adjusting the pH value of the traditional Chinese medicine extract concentrate to 7.5-10, heating the aqueous dispersion and the traditional Chinese medicine extract concentrate after the pH value is adjusted to 50-70°C respectively and then mixing them, drying, adding or not adding auxiliary materials, and granulating to obtain the traditional Chinese medicine granules, which have good taste-masking effect, small amount of auxiliary materials, simple preparation process, can effectively mask the bitterness of the medicine, and can be evenly dispersed in water, so that the patient will not have a foreign body sensation when taking the medicine, and at the same time will not affect the release and absorption of the medicine.

[0028] The inventors have found that when the aqueous dispersion and the concentrated Chinese herbal extract with adjusted pH value are mixed and then heated to 50-70°C, more film-forming materials are precipitated, resulting in poor taste-masking effect. However, by heating the aqueous dispersion with the above-mentioned specific composition and the concentrated Chinese herbal extract with pre-adjusted pH value to 7.5-10 to 50-70°C and then mixing, drying and granulating, not only the taste-masking effect of the particles is significantly improved, but also less precipitation is produced during the preparation process, so that the solubility (or water solubility) of the particles is good and the dispersibility is significantly improved.

[0029] In addition, the drying of the extract concentrate and the preparation of the microcapsule taste-masking process are completed through one drying process, saving process steps and avoiding losses and energy consumption.

[0030] 2. The preparation method of the traditional Chinese medicine granules provided by the present invention controls the ratio of the mass of the dry matter in the traditional Chinese medicine extract concentrate to the total mass of sodium lauryl sulfate, stearic acid and Eudragit® EPO in the aqueous dispersion to be 1.2:1 to 2:1, thereby minimizing the amount of auxiliary materials used and exerting a better taste-masking effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0032] Figure 1 This is a photograph of the sample after sieving in step (3) of Example 1 of the present invention;

[0033] Figure 2 This is a photograph of the sample after sieving in step (3) of Example 3 of the present invention;

[0034] Figure 3 This is a photo of the sample after sieving in step (3) of comparative example 2 of the present invention;

[0035] Figure 4 This is a photograph of the water dispersion and lotus leaf extract concentrate mixed in Comparative Example 3 of the present invention. DETAILED DESCRIPTION

[0036] The following examples are provided for a better understanding of the present invention, but are not intended to limit the best mode of implementation, nor to limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention.

[0037] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be purchased commercially.

[0038] Example 1 Houttuynia cordata formula granules

[0039] This embodiment provides a method for preparing houttuynia cordata formula granules, comprising the following steps:

[0040] (1) Weigh 100 g of Eudragit EPO, 20 g of sodium lauryl sulfate, and 20 g of stearic acid, add them to 1500 ml of purified water while stirring, and continue stirring and dispersing for 1.0 h after the addition to prepare an aqueous dispersion.

[0041] (2) Weigh 2 kg of Houttuynia cordata slices, add water and boil twice, add 18 times the amount of the slices of water to the first decoction and boil for 2 h, add 15 times the amount of the slices of water to the second decoction and boil for 1.5 h, filter the filtrate with a 150-mesh filter, and concentrate the filtrate at 65° C. to obtain a concentrated solution, dilute the concentrated solution with purified water to a relative density of 1.05 (60° C.), adjust the pH value to 8.5 with a 2% by mass NaOH solution, and obtain a Houttuynia cordata extract concentrate with a pH value of 8.5.

[0042] (3) The aqueous dispersion obtained in step (1) is heated to 68°C for standby use. Weigh 200g of Houttuynia cordata extract concentrate with a pH value of 8.5 and heat it to 68°C. Slowly add it to the 68°C aqueous dispersion while stirring. After mixing evenly, pass through an 80-mesh sieve and spray dry. The inlet air temperature is 150°C. Adjust the injection speed so that the outlet air temperature is maintained at 85°C to obtain Houttuynia cordata spray-dried powder. Weigh 40g of maltodextrin and mix evenly with the Houttuynia cordata spray-dried powder and perform dry granulation to obtain Houttuynia cordata formula granules.

[0043] Figure 1 This is a photo of the sample after sieving in step (3) of this embodiment. It can be seen from the photo that only a small amount of film-forming material is precipitated. Compared with Comparative Example 2 ( Figure 3 ) and Comparative Example 3 ( Figure 4 )’s dispersibility was significantly improved.

[0044] Embodiment 2 earthworm formula granules

[0045] This embodiment provides a method for preparing earthworm formula granules, comprising the following steps:

[0046] (1) Weigh 100 g of Eudragit EPO, 20 g of sodium lauryl sulfate, and 20 g of stearic acid, add them to 2000 ml of purified water while stirring, and continue stirring and dispersing for 1 hour after the addition to prepare an aqueous dispersion.

[0047] (2) Weigh 1 kg of earthworm slices, add water and boil twice, add 12 times the amount of the slices of water for the first decoction and boil for extraction for 1 hour, add 10 times the amount of the slices of water for the second decoction and boil for extraction for 1 hour, filter the filtrate with a 150-mesh filter, and concentrate the filtrate at 65° C. to obtain a concentrated solution, dilute the concentrated solution with purified water to a relative density of 1.06 (60° C.), adjust the pH value to 7.8 with a 2% by mass NaOH solution, and obtain an earthworm extract concentrate with a pH value of 7.8.

[0048] (3) The aqueous dispersion obtained in step (1) is heated to 50°C for standby use. Weigh 180g of the dry matter mass of the earthworm extract concentrate with a pH value of 7.8, heat it to 50°C, slowly add it to the 50°C aqueous dispersion while stirring, mix well, pass through an 80-mesh sieve, and spray dry. The inlet air temperature is 163°C. Adjust the injection speed so that the outlet air temperature is maintained at 80°C to obtain earthworm spray-dried powder. Weigh 40g of maltodextrin and mix well with the earthworm spray-dried powder, then dry granulate it to obtain earthworm formula granules.

[0049] Example 3 Lotus leaf formula granules

[0050] This embodiment provides a method for preparing lotus leaf formula granules, comprising the following steps:

[0051] (1) Weigh 100 g of Eudragit EPO, 20 g of sodium lauryl sulfate, and 20 g of stearic acid, add them to 1200 ml of purified water while stirring, and continue stirring and dispersing for 1 hour after the addition to prepare an aqueous dispersion.

[0052] (2) Weigh 2.5 kg of lotus leaf slices, add water and boil twice, add 14 times the amount of slices of water for the first decoction and boil for extraction for 1.5 h, add 11 times the amount of slices of water for the second decoction and boil for extraction for 1 h, filter with a 150-mesh filter, concentrate at 65° C. to obtain a concentrate, dilute the concentrate with purified water to a relative density of 1.04 (60° C.), adjust the pH value to 9.0 with a 2% by mass NaOH solution, and obtain a lotus leaf extract concentrate with a pH value of 9.0.

[0053] (3) The aqueous dispersion obtained in step (1) is heated to 65°C for standby use. Weigh 250g of lotus leaf extract concentrate with a pH value of 7.8 and heat it to 65°C. Slowly add it to the 65°C aqueous dispersion while stirring. After mixing evenly, pass it through an 80-mesh sieve and spray dry it. The inlet air temperature is 163°C. Adjust the injection speed so that the outlet air temperature is maintained at 85°C to obtain lotus leaf spray-dried powder. Weigh 40g of maltodextrin and mix it evenly with the lotus leaf spray-dried powder, then dry granulate it to obtain lotus leaf formula granules.

[0054] Figure 2This is a photo of the sample after sieving in step (3) of this embodiment. It can be seen from the photo that only a small amount of film-forming material is precipitated. Compared with Comparative Example 2 ( Figure 3 ) and Comparative Example 3 ( Figure 4 )’s dispersibility was significantly improved.

[0055] Comparative Example 1

[0056] This comparative example provides a method for preparing houttuynia cordata formula granules, which is different from Example 1 only in that no taste masking treatment is performed, and specifically comprises the following steps:

[0057] (1) Weigh 2 kg of Houttuynia cordata slices, add 18 times the amount of water to the slices for the first decoction and boil for extraction for 2 h, add 15 times the amount of water to the slices for the second decoction and boil for extraction for 1.5 h, filter the filtrate with a 150-mesh filter, concentrate the filtrate at 65° C. to obtain a concentrated solution, dilute the concentrated solution with purified water to a relative density of 1.05 (60° C.), adjust the pH value to 8.5 with a 2% by mass NaOH solution, and obtain a Houttuynia cordata extract concentrated solution with a pH value of 8.5.

[0058] (2) Weigh 200 g of Houttuynia cordata extract concentrate with a pH value of 8.5, heat it to 68°C, pass it through an 80-mesh sieve, and spray dry it. The inlet air temperature is 150°C, and the feed rate is adjusted to maintain the outlet air temperature at 85°C to obtain Houttuynia cordata spray-dried powder. Weigh 40 g of maltodextrin and mix it evenly with the Houttuynia cordata spray-dried powder, and then dry granulate it to obtain Houttuynia cordata formula granules.

[0059] Comparative Example 2

[0060] This comparative example provides a method for preparing houttuynia cordata formula granules, which is basically the same as the preparation method of Example 1, except that the pH value of the houttuynia cordata extract concentrate in step (2) is not adjusted by an alkaline solution, and the houttuynia cordata extract concentrate diluted with purified water (the pH value is 6.46 after detection) is directly used in step (3), and the water dispersion and the houttuynia cordata extract concentrate are not heated. After the two are evenly mixed, a large amount of film-forming material is precipitated (see Figure 3 As shown in the figure, more precipitates could not pass through the sieve, and after sieving, spray drying was performed, the inlet air temperature was 150°C, and the feed rate was adjusted to maintain the outlet air temperature at 85°C to obtain Houttuynia cordata spray-dried powder. 40 g of maltodextrin was weighed and mixed evenly with Houttuynia cordata spray-dried powder, and then dry granulation was performed to obtain Houttuynia cordata formula granules.

[0061] Comparative Example 3

[0062] This comparative example provides a method for preparing lotus leaf formula granules, which is basically the same as the preparation method of Example 3, except that the lotus leaf extract concentrate in step (2) is not adjusted with an alkaline solution to adjust the pH value, and step (3) directly uses the lotus leaf extract concentrate diluted with purified water (the pH value is 5.39 after detection).

[0063] According to step (3) of Example 3, the aqueous dispersion and the lotus leaf extract concentrate were heated and mixed separately, and a large amount of precipitation was found to appear (see Figure 4 The mixture was sieved and spray dried, the inlet air temperature was 163°C, and the feed rate was adjusted to maintain the outlet air temperature at 85°C to obtain Houttuynia cordata spray dried powder. 40 g of maltodextrin was weighed and mixed evenly with Houttuynia cordata spray dried powder, and then dry granulated to obtain Houttuynia cordata formula granules.

[0064] Experimental Example 1 Sensory Evaluation

[0065] The formula granules prepared in each embodiment and comparative example were used as experimental objects to conduct taste tests, and the corresponding scoring criteria are shown in Table 1 below:

[0066] Table 1 Test scoring criteria

[0067]

[0068] A total of 10 people participated in the sensory test. All the participants had been engaged in the R&D of traditional Chinese medicine for more than 2 years. The scores were averaged. The test results are shown in the following table:

[0069] The corresponding evaluation results are shown in Table 2 below.

[0070] Table 2 Sensory evaluation results

[0071] project Taste (points) Flavor (points) Comprehensive evaluation Example 1 7.6 7.9 8.0 Example 2 7.4 7.1 7.7 Example 3 7.3 8.1 7.9 Comparative Example 1 4.5 6.9 5.7 Comparative Example 2 4.3 6.5 5.4 Comparative Example 3 4.3 6.6 5.5

[0072] It can be seen from the results in the above table that, compared with Comparative Examples 1-3, the taste masking effect of the particles obtained by the preparation methods provided in the embodiments of the present invention is significantly improved.

[0073] Experimental Example 2: Solubility Investigation

[0074] Take 10g of the granules of Example 1 and Comparative Example 1 respectively, add 200ml of hot water, stir for 5 minutes, and observe immediately, it can be seen that both groups of granules are completely dissolved. The results show that the taste masking treatment by the method of the present invention does not have an adverse effect on the solubility of the granules, and still meets the requirements of the pharmacopoeia.

[0075] Experimental Example 3 Dissolution

[0076] The formulated granules prepared in Example 1 and Comparative Example 1 were used as experimental objects for dissolution test. According to the dissolution determination method (Appendix XC Method 2 of Part II of the 2020 Edition of the Chinese Pharmacopoeia), an appropriate amount of formulated granules was taken, and 900 ml of 0.1 mol / L hydrochloric acid solution was used as the solvent. The speed was 50 r / min, and the samples were filtered at 5 min, 10 min and 20 min. The subsequent filtrate was taken as the test solution, and the content of quercetin in the test solution was determined by referring to the method under the content determination item in the Houttuynia cordata formula granules (for specific methods, see the National Drug Standard YBZ-PFKL-2021145 of the State Food and Drug Administration), and the dissolution was calculated. Six groups were tested in parallel in Example 1 and Comparative Example 1, and the average value and RSD value were calculated. The results are as follows:

[0077] Table 3 Average dissolution test results

[0078] Sample name 5min 10min 20min Example 1 62％ 87％ 98％ Comparative Example 1 61％ 89％ 99％ RSD% 0.81 1.14 0.51

[0079] The above results indicate that the taste masking treatment using the method of the present invention has no adverse effect on the dissolution rate of the granules, and the granules still meet the requirements of the pharmacopoeia and have good dissolution performance.

[0080] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the invention.

Claims

1. A method for preparing Chinese medicine granules, characterized in that: The steps include: Preparation of aqueous dispersion: Sodium lauryl sulfate, stearic acid, Eudragit EPO and water are mixed to prepare aqueous dispersion; Preparation of Chinese medicine granules: adjust the pH value of the Chinese medicine extract concentrate to 7.5-10, heat the water dispersion and the Chinese medicine extract concentrate after pH adjustment to 50-70°C respectively and then mix them, dry, add or not add auxiliary materials, and granulate to obtain Chinese medicine granules.

2. The method for preparing the Chinese medicine granules according to claim 1, characterized in that: The mass ratio of the Eudragit EPO, sodium lauryl sulfate and stearic acid is 60-80:10-20:10-20.

3. The method for preparing the Chinese medicine granules according to claim 1 or 2, characterized in that: In the aqueous dispersion, the mass percentage of Eudragit EPO to the mass of water is 5-10%.

4. The method for preparing the Chinese medicine granules according to any one of claims 1 to 3, characterized in that: During the preparation of the aqueous dispersion, sodium lauryl sulfate, stearic acid and Eudragit EPO were added into water while stirring, and stirring was continued for more than 1 hour after the addition.

5. The method for preparing the Chinese medicine granules according to any one of claims 1 to 4, characterized in that: The Chinese medicine extract concentrate further comprises the step of adding water to dilute the concentrate to a relative density of 1.04-1.1 at 50-70° C. before adjusting the pH value.

6. The method for preparing the Chinese medicine granules according to any one of claims 1 to 5, characterized in that: In the preparation process of the Chinese medicine granules, an alkaline solution is used to adjust the pH value of the Chinese medicine extract concentrate; Preferably, the alkaline solution is selected from one or more of NaOH solution, Na2CO3 solution, KOH solution, and NaHCO3 solution; Preferably, the mass concentration of the alkaline solution is 1-5%.

7. The method for preparing the Chinese medicine granules according to any one of claims 1 to 6, characterized in that: The granulation is dry granulation; and / or the Chinese medicine extract concentrate is selected from at least one of Houttuynia cordata extract concentrate, Pheretima extract concentrate, and Lotus leaf extract concentrate.

8. The method for preparing the Chinese medicine granules according to any one of claims 1 to 7, characterized in that: The auxiliary material is one or more of dextrin, lactose and maltodextrin; the preferred auxiliary material is maltodextrin.

9. The method for preparing the Chinese medicine granules according to any one of claims 1 to 8, characterized in that: During the preparation of the Chinese medicine granules, the ratio of the mass of dry matter in the Chinese medicine extract concentrate to the total mass of sodium dodecyl sulfate, stearic acid and Eudragit® EPO in the water dispersion is 1.2:1 to 2:

1.

10. A Chinese medicine granule obtained by the preparation method according to any one of claims 1 to 9, preferably, the Chinese medicine granule is selected from at least one of Houttuynia cordata formula granules, Pheretima formula granules, and Lotus leaf formula granules.

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