Child-type Xiaochaihu granules and a preparation method thereof

Abstract

This invention provides a pediatric Xiaochaihu granule and its preparation method. The Xiaochaihu granules are prepared from a dry extract powder of a traditional Chinese medicine composition, sucrose, soluble starch, and flavoring as raw materials. The weight ratio of the total weight of sucrose and soluble starch to the weight of the dry extract powder of the traditional Chinese medicine composition is (2-5):1, the weight ratio of sucrose to soluble starch is 1:1.5-1.5:1, and the weight ratio of flavoring to the dry extract powder of the traditional Chinese medicine composition is (0-5):(100-500). The dry extract powder of the traditional Chinese medicine composition is prepared by extracting the active ingredients from the raw materials and then drying the resulting extract. Through optimized formulation, this invention's Xiaochaihu granules maintain a good taste while significantly reducing the total amount of excipients and sucrose. It also ensures that the prepared Xiaochaihu granules are uniform in size and appropriately firm, improving children's medication adherence and safety, and reducing the risk of inactive excipient intake and excessive sucrose intake in children during clinical medication use.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a children's type of Xiaochaihu granules and its preparation method. Background Technology

[0002] Xiao Chai Hu Granules are a traditional Chinese medicine developed based on the famous formula Xiao Chai Hu Tang from the "Treatise on Cold Damage" written by Zhang Zhongjing, the "Sage of Medicine." The original formula, Xiao Chai Hu Tang, is traditionally summarized in Chinese medicine as follows: "Xiao Chai Hu Tang harmonizes and resolves, with Pinellia, Ginseng, and Licorice as adjuncts; further enhanced with Scutellaria, Ginger, and Jujube, this formula is the foundation for Shao Yang syndrome." In the 1990s, Guangzhou Baiyunshan Guanghua Pharmaceutical Co., Ltd. improved Xiao Chai Hu Tang into Xiao Chai Hu Granules. Composed of Bupleurum, Scutellaria, Ginger-processed Pinellia, Codonopsis, Ginger, Licorice, and Jujube, these granules benefit from a scientifically sound formula. They can relieve exterior symptoms, clear heat, soothe the liver, and harmonize the stomach. They are used for exogenous diseases, specifically Shao Yang syndrome, characterized by alternating chills and fever, fullness and discomfort in the chest and ribs, loss of appetite, irritability, nausea, bitter taste in the mouth, and dry throat.

[0003] Xiao Chai Hu Tang is a frequently used prescription in clinical practice, with an extremely wide range of applications. Xiao Chai Hu Granules, derived from it, have become a widely used and highly praised cold and fever remedy among ordinary people in my country today. Besides treating colds and fevers, Xiao Chai Hu Granules also have antiviral effects, regulate the spleen and stomach, and enhance the body's immune function, showing broad clinical application prospects.

[0004] However, Xiao Chai Hu granules, a traditional Chinese medicine formula passed down through generations, currently lack a dosage form specifically developed for children. Children's medicines refer to medicines specifically for use by minors under the age of 14. Currently, the excipients used in commercially available Xiao Chai Hu granules fall into three categories: First, sucrose, which can easily cause tooth decay in children with high doses and frequent use; second, lactose, as some children are lactose intolerant; and third, other excipients such as dextrin and mannitol, as mannitol has a potential laxative effect in children. Excessive intake of any of these excipients is not advisable for children who are still developing.

[0005] In addition, most current methods for preparing Chinese medicine granules involve wet granulation of Chinese medicine extract followed by boiling and drying. This method relies heavily on manual operation and subjective judgment of the soft material's state. While it has high operational adaptability, it is not very stable and suffers from problems such as difficulty in granulation and drying, uneven particle size, large content differences, and the need for high-concentration ethanol to assist in granulation.

[0006] Therefore, it is necessary to develop a children's version of Xiaochaihu granules specifically for children, and to improve the granule production process, simplify production operations, and improve the quality, efficiency, and stability of granule production. Summary of the Invention

[0007] Based on this, the purpose of the present invention is to provide a Xiaochaihu granule and its preparation method; the Xiaochaihu granule can maintain a good taste after greatly reducing the total amount of excipients and sucrose, while ensuring that the prepared Xiaochaihu granules are uniform, loose and suitable, and can also improve children's medication compliance and safety.

[0008] In a first aspect, the present invention provides a Xiaochaihu granule, wherein the Xiaochaihu granule is prepared from a dry extract powder of a traditional Chinese medicine composition, sucrose, soluble starch and flavoring as raw materials; wherein the total weight ratio of sucrose and soluble starch to the weight ratio of the dry extract powder of the traditional Chinese medicine composition is (2-5):1, the weight ratio of sucrose to soluble starch is 1:1.5-1.5:1, and the weight ratio of flavoring to the dry extract powder of the traditional Chinese medicine composition is (0-5):(100-500);

[0009] The herbal composition dry powder is prepared by extracting the active ingredients and then drying the resulting clear paste. The active ingredients are extracted from the following raw materials in parts by weight: Bupleurum chinense 100-200 parts, Scutellaria baicalensis 40-70 parts, Pinellia ternata 40-70 parts, Codonopsis pilosula 40-70 parts, fresh ginger 40-70 parts, licorice root 40-70 parts, and jujube 40-70 parts.

[0010] In some embodiments, the total weight ratio of the sucrose and soluble starch to the weight ratio of the dry extract powder of the traditional Chinese medicine composition is (3-4):1.

[0011] In some embodiments, the weight ratio of sucrose to soluble starch is 1:1.5 to 1:1.

[0012] In some embodiments, the weight ratio of the fragrance to the dry powder of the traditional Chinese medicine composition is (1-5):(100-500), more preferably (1-2):(100-300); and even more preferably (1-2):(100-200).

[0013] In some embodiments, the active ingredients are extracted from the following raw materials in parts by weight: Bupleurum chinense 150-200 parts, Scutellaria baicalensis 56-70 parts, Pinellia ternata 56-70 parts, Codonopsis pilosula 56-70 parts, fresh ginger 56-70 parts, licorice 56-70 parts, and jujube 56-70 parts; preferably, the active ingredients of the dry extract powder of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: Bupleurum chinense 150±5 parts, Scutellaria baicalensis 56±5 parts, Pinellia ternata 56±5 parts, Codonopsis pilosula ±5 parts, fresh ginger 56±5 parts, licorice 56±5 parts, and jujube 56±5 parts.

[0014] In some embodiments, the Xiaochaihu granules are prepared from the following raw materials: a dry extract of traditional Chinese medicine composition, sucrose, soluble starch, and flavoring. The sucrose, the dry extract of traditional Chinese medicine composition, and the soluble starch are fed into a one-step granulation device, and the air inlet temperature is set to 70℃-100℃ for preheating. A wetting agent is sprayed in for atomized granulation, followed by drying, sieving, adding flavoring, and mixing to obtain the Xiaochaihu granules.

[0015] In some embodiments, the inlet air temperature of the granulation equipment is set to 80°C-90°C.

[0016] In some embodiments, the temperature is preheated to 40°C-60°C, preferably 45°C-55°C.

[0017] In some embodiments, the atomization pressure is 2.0 bar to 4.0 bar, preferably 2.0 bar to 3.0 bar.

[0018] A second aspect of the present invention provides a method for preparing Xiaochaihu granules as described above, comprising the following steps:

[0019] ① Preheating: Take the sucrose, the dry extract powder of the traditional Chinese medicine composition and the soluble starch, put them into the one-step granulation equipment, control the boiling fluidization of the materials, and preheat the materials;

[0020] ② Granulation: After the material is preheated, control the material to boil and fluidize, and spray the wetting agent evenly for atomization granulation. After granulation, dry to obtain dry granules.

[0021] ③ Screening: The dry particles are screened by a vibrating screener;

[0022] ④Total mixing: Add flavoring to the dry granules obtained by sieving and mix to obtain the Xiaochaihu granules.

[0023] In some embodiments, the inlet air temperature of the granulation equipment is set to 70℃-100℃, preferably 80℃-90℃.

[0024] In some embodiments, in step ① the material is preheated to 40°C-60°C, preferably 45°C-55°C.

[0025] In some embodiments, the atomization pressure in step ② is 2.0 bar to 4.0 bar, preferably 2.0 bar to 3.0 bar.

[0026] In some embodiments, the wetting agent in step ② is selected from water or ethanol with a concentration not exceeding 30%; preferably, the wetting agent is water.

[0027] In some embodiments, the airflow distribution plate of the granulation equipment is a cyclone sintering plate.

[0028] In some embodiments, the air inlet volume of the granulation equipment is set to 1000 m³ / h. 3 / h-2000M 3 / h.

[0029] In some embodiments, the flow rate of the wetting agent in step ② is 2 kg / min to 6 kg / min.

[0030] In some embodiments, the granulation time in step ② is 5 min to 15 min.

[0031] In some embodiments, the drying in step ② is boiling drying.

[0032] This invention provides a Xiaochaihu granule that is highly suitable for pediatric patients. Addressing the need for children to avoid excessive excipient intake and their requirement for a pleasant taste, this invention involves extensive research into the formulation. The process involves preparing a dry extract powder from the active ingredients extracted from traditional Chinese medicine raw materials, compounding it with suitable excipients sucrose and soluble starch, and further optimizing the total amount of the dry extract powder and excipients, as well as the ratio of sucrose and soluble starch, to obtain the final Xiaochaihu granule formulation. The addition of a suitable amount of flavoring not only acts as a taste enhancer to improve the palatability of the medicine, but also, together with sucrose and soluble starch, acts as an excipient in the dry extract powder. Together, these three elements further ensure the quality of subsequent granulation of the dry extract powder, resulting in Xiaochaihu granules that are uniform, compact, and have good solubility.

[0033] Meanwhile, this invention also optimizes the preparation method of Xiao Chai Hu granules. The preparation method described in this invention enables one-step granulation, continuous, and automated production of Xiao Chai Hu granules. In the preparation of Xiao Chai Hu granules, this invention uses dry extract powder instead of traditional extract for granulation. The extract obtained after extracting the active ingredients from the Chinese herbal raw materials is spray-dried to obtain dry extract powder. Spray drying enables automated feeding and continuous production. Furthermore, the optimized formula simplifies the raw materials for preparing Xiao Chai Hu granules. The mixing, granulation, and drying processes can be completed in one step by adding the dry extract powder, sucrose, and soluble starch, greatly simplifying production operations and improving efficiency. Moreover, the entire process from raw material feeding to granule production is carried out in a closed system, better meeting GMP requirements.

[0034] Furthermore, this invention optimizes the one-step granulation method. By controlling the inlet air temperature of the granulation equipment, the material is preheated to a suitable temperature before being sprayed with a wetting agent under appropriate pressure for atomized granulation. This ensures easy granulation, uniform particle size, suitable density, narrow particle size distribution, good repeatability between different batches of Xiaochaihu granules, and high granule yield. Based on this, further control of the type of wetting agent can avoid an excessive amount of fine powder or coarse particles due to material stickiness during granulation, further improving particle uniformity and yield.

[0035] The preparation method of Xiaochaihu granules of the present invention effectively solves the problems of difficult granulation and drying, uneven particle size, large differences in the content of effective ingredients and poor repeatability, the need for high concentration of ethanol to assist granulation and low yield by continuously controlling multiple key related parameters.

[0036] This invention, through further improvements in both the formulation and preparation method, results in Xiaochaihu granules with uniform particle size and good formability. It also improves medication adherence in children while effectively reducing the risk of inactive excipient intake and excessive sucrose intake in children during clinical medication use, thus increasing safety. The Xiaochaihu granules possess antipyretic, anti-inflammatory, analgesic, and gastrointestinal regulating effects, making them highly suitable for treating diseases including childhood gastroenteritis. Detailed Implementation

[0037] Unless otherwise specified, the experimental methods described in the following embodiments of the present invention are generally performed under conventional conditions or as recommended by the manufacturer. All commonly used chemical reagents used in the embodiments are commercially available products.

[0038] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to limit the invention.

[0039] The terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion. For example, a process, method, apparatus, product, or device that includes a series of steps is not limited to the steps or modules listed, but may optionally include steps not listed, or may optionally include other steps inherent to such process, method, product, or device.

[0040] In this invention, the term "and / or" describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent three cases: A existing alone, A and B existing simultaneously, and B existing alone. The character " / " generally indicates that the preceding and following related objects have an "or" relationship.

[0041] One embodiment of the present invention relates to a Xiaochaihu granule, which is prepared from a dry extract of a traditional Chinese medicine composition, sucrose, soluble starch, and flavoring as raw materials; the weight ratio of the total weight of sucrose and soluble starch to the weight of the dry extract of the traditional Chinese medicine composition is (2-5):1, the weight ratio of sucrose to soluble starch is 1:1.5-1.5:1, and the weight ratio of flavoring to the dry extract of the traditional Chinese medicine composition is (0-5):(100-500).

[0042] The herbal composition dry powder is prepared by extracting the active ingredients and then drying the resulting clear paste. The active ingredients are extracted from the following raw materials in parts by weight: Bupleurum chinense 100-200 parts, Scutellaria baicalensis 40-70 parts, Pinellia ternata 40-70 parts, Codonopsis pilosula 40-70 parts, fresh ginger 40-70 parts, licorice root 40-70 parts, and jujube 40-70 parts.

[0043] Considering that children should not consume excessive amounts of excipients and their need for a good taste, the inventors of this invention have optimized the formula based on years of clinical experience and extensive research. The formula involves preparing a dry extract powder from the active ingredients extracted from traditional Chinese medicine raw materials, then compounding it with suitable excipients sucrose and soluble starch. The total amount of the dry extract powder and excipients, as well as the ratio of sucrose and soluble starch, are further optimized to obtain the preparation formula for Xiao Chai Hu granules. In this formula, the addition of an appropriate amount of flavoring not only acts as a flavoring agent to enhance the taste of the medicine, but also, together with sucrose and soluble starch, acts as an excipient in the dry extract powder. Together, these three ingredients further ensure the quality of subsequent granulation, resulting in Xiao Chai Hu granules that are uniform, compact, and have good solubility.

[0044] In some embodiments, the total weight ratio of sucrose and soluble starch to the dry extract powder of the traditional Chinese medicine composition is (3-4):1; the weight ratio of sucrose to soluble starch is 1:1.5-1:1. The inventors have found that the total weight ratio of excipients (sucrose and soluble starch) to the dry extract powder of the traditional Chinese medicine composition, as well as the weight ratio of excipients to sucrose and soluble starch, significantly affects the uniformity of the granules and the yield. When the proportion of dry extract powder of the traditional Chinese medicine composition is too high, the material becomes sticky during granulation, resulting in more coarse particles and a decreased yield. When the proportion of sucrose in the excipients is too high, the material becomes sticky during granulation, resulting in more coarse particles and a decreased yield; when the proportion of soluble starch in the excipients is too high, the granules are loose and brittle, and the amount of fine powder increases.

[0045] In some embodiments, the preparation method of the dry extract powder of the traditional Chinese medicine composition is as follows: obtaining an extract of the active ingredients of the raw materials, concentrating, filtering, and drying to obtain the dry extract powder of the traditional Chinese medicine composition.

[0046] In some preferred embodiments, the method for preparing the dry extract powder of the traditional Chinese medicine composition includes the following steps:

[0047] (1) Add the Bupleurum, Scutellaria baicalensis, Codonopsis pilosula, jujube and licorice to extraction solvent A, extract 1 to 3 times, combine the extracts, concentrate, filter, and obtain filtrate A;

[0048] (2) Add the ginger-processed Pinellia ternata and fresh ginger to extraction solvent B, soak, percolate, concentrate, filter, and obtain filtrate B;

[0049] (3) Combine the filtrate A and filtrate B, concentrate, filter, and obtain a clear paste;

[0050] (4) The ointment is dried to obtain the dry powder of the traditional Chinese medicine composition.

[0051] In some embodiments, the extraction solvent A in step (1) is water, and the extraction is a decoction extraction.

[0052] In some embodiments, step (1) includes the following steps: decocting Bupleurum, Scutellaria baicalensis, Codonopsis pilosula, Jujube and Glycyrrhiza uralensis with water to extract 1-3 times, preferably 2-3 times; the weight ratio of the medicinal materials extracted in the first decoction to the weight of water is 1:(8-12), and the weight ratio of the medicinal materials extracted in the second and third decoctions to the weight of water is 1:(6-10), with each decoction taking 1-3 hours; combining the decoctions, filtering, concentrating the filtrate under reduced pressure to a concentration with a relative density of 1.00-1.20, filtering, and obtaining filtrate A.

[0053] In some embodiments, the extraction solvent B in step (2) is ethanol, preferably 50%-90% ethanol.

[0054] In some embodiments, step (2) includes the following steps: adding 50%-90% ethanol to Pinellia ternata and ginger, soaking for 12-36 hours, with the weight ratio of the soaked medicinal materials to the 50%-90% ethanol being 1:(4-8); after soaking, adding 50%-90% ethanol for percolation, with the weight ratio of the percolated medicinal materials to the added 50%-90% ethanol being 1:(2-6); combining the percolates, reducing the pressure to recover ethanol to a relative density of 1.00-1.20, filtering, and obtaining filtrate B.

[0055] In some embodiments, in step (3), the concentration is reduced to a relative density of 1.10-1.30.

[0056] In some embodiments, the concentration is vacuum concentration; preferably, the vacuum degree of vacuum concentration is -0.02 MPa to -0.09 MPa, and the temperature is <95°C.

[0057] In some embodiments, the ointment is spray-dried in step (4). Preferably, the inlet air temperature of the spray dryer is 110℃-170℃, the outlet air temperature is 70℃-100℃, and the liquid inlet rate is 50mL / min-300mL / min.

[0058] In some embodiments, the loss on drying in step (4) is ≤10%.

[0059] In some embodiments, the Xiaochaihu granules are prepared from the following raw materials: a dry extract of traditional Chinese medicine composition, sucrose, soluble starch, and flavoring. The sucrose, the dry extract of traditional Chinese medicine composition, and the soluble starch are fed into a one-step granulation device, and the air inlet temperature is set to 70℃-100℃ for preheating. A wetting agent is sprayed in for atomized granulation, followed by drying, sieving, adding flavoring, and mixing to obtain the Xiaochaihu granules.

[0060] In some preferred embodiments, the temperature is preheated to 40°C-60°C, preferably 45°C-55°C.

[0061] In some preferred embodiments, the atomization pressure is 2.0 bar to 4.0 bar, preferably 2.0 bar to 3.0 bar.

[0062] The inventors discovered that the inlet air temperature of the granulation equipment has no significant effect on the particle content, but it does have a significant impact on particle uniformity and yield. At lower inlet air temperatures (60℃), the material exhibits stickiness during granulation, resulting in more coarse particles and a lower yield. At higher inlet air temperatures (100℃), the wetting agent dries too quickly during granulation, failing to fully wet the material and resulting in more fine powder particles. Simultaneously, the higher the inlet air temperature, the shorter the drying time. In this invention, the preferred inlet air temperature is 70℃-100℃, more preferably 80℃-90℃, which results in uniform particle size, higher yield, and shorter drying time, thus improving both production efficiency and product quality. In addition to controlling the inlet air temperature, it is necessary to further control the temperature of the material used for granulation within a suitable range. Granulation at different material temperatures did not result in significant differences in particle moisture content. However, at lower material temperatures (40-45℃), the material exhibited stickiness during granulation, leading to a higher proportion of coarse particles. At higher material temperatures (55-60℃), the wetting agent dried rapidly during granulation, resulting in insufficient wetting of the material and a higher proportion of fine powder particles. A material temperature of 45-55℃ was preferred as the preheating endpoint temperature and the starting temperature for granulation spraying. After preheating the granulating material to a suitable temperature, appropriate granulation atomization pressure was crucial for ensuring particle uniformity and yield. At lower atomization pressures (1.0 bar), the granulation droplets were larger, causing material stickiness and agglomeration, resulting in "bed collapse." At higher atomization pressures (5.0 bar), the granulation droplets were smaller, resulting in faster drying, insufficient wetting of the material, finer particles, and a decreased yield. A preferred atomization pressure was 2.0 bar-4.0 bar, more preferably 2.0 bar-3.0 bar, to achieve good atomization effects and ensure particle uniformity and yield. By controlling the inlet air temperature of the granulation equipment, the material is preheated to a suitable temperature and then atomized and granulated under a specific pressure. This ensures easy granulation, uniform particle size, suitable density, narrow particle size distribution, good repeatability between different batches of Xiaochaihu granules, and a high particle yield.

[0063] In some preferred embodiments, the wetting agent is selected from water or ethanol with a concentration not exceeding 30%; preferably, the wetting agent is water. The inventors have found that, based on the above operations, further controlling the type of wetting agent can avoid an excessive amount of fine powder or coarse particles due to material stickiness during granulation, thereby further improving particle uniformity and yield.

[0064] One embodiment of the present invention relates to a method for preparing Xiaochaihu granules as described above, comprising the following steps:

[0065] ① Preheating: Take the sucrose, the dry extract powder of the traditional Chinese medicine composition and the soluble starch, put them into the one-step granulation equipment, control the boiling fluidization of the materials, and preheat the materials;

[0066] ② Granulation: After the material is preheated, control the material to boil and fluidize, and spray the wetting agent evenly for atomization granulation. After granulation, dry to obtain dry granules.

[0067] ③ Screening: The dry particles are screened by a vibrating screener;

[0068] ④Total mixing: Add flavoring to the dry granules obtained by sieving and mix to obtain the Xiaochaihu granules.

[0069] This invention also optimizes the preparation method of Xiao Chai Hu granules. The preparation method described in this invention enables one-step granulation of Xiao Chai Hu granules, achieving continuous and automated production. In the preparation of Xiao Chai Hu granules, this invention uses dry extract powder instead of traditional extract for granulation. The extract obtained after extracting the active ingredients from the Chinese herbal raw materials is spray-dried to obtain dry extract powder. Spray drying enables automated feeding and continuous production. Furthermore, the optimized formula simplifies the raw materials for preparing Xiao Chai Hu granules. The mixing, granulation, and drying processes can be completed in one step by adding the dry extract powder, sucrose, and soluble starch, greatly simplifying production operations and improving efficiency. Moreover, the entire process from raw material feeding to granule production is carried out in a closed system, better meeting GMP requirements.

[0070] This invention achieves high yield, uniform particle size, suitable density, and narrow particle size distribution of the prepared Bupleurum chinense granules through continuous control of multiple key related parameters. It effectively solves the problems of existing granulation and drying processes, such as uneven particle size, large differences in the content of effective ingredients, poor repeatability, the need for high-concentration ethanol to assist in granulation, and low yield.

[0071] This invention, through further improvements in both the formulation and preparation method, results in Xiaochaihu granules with uniform particle size and good formability. It also improves medication adherence in children while effectively reducing the risk of inactive excipient intake and excessive sucrose intake in children during clinical medication use, thus increasing safety. The Xiaochaihu granules possess antipyretic, anti-inflammatory, analgesic, and gastrointestinal regulating effects, making them highly suitable for treating diseases including childhood gastroenteritis.

[0072] The following description is based on specific implementation methods.

[0073] Example 1

[0074] This embodiment provides a children's type of Xiaochaihu granules, which are prepared by the following method:

[0075] Part 1: Preparation of Dry Powder

[0076] ①Prescription composition: Bupleurum 150kg, Pinellia ternata 56kg, Scutellaria baicalensis 56kg, Codonopsis pilosula 56kg, Glycyrrhiza uralensis 56kg, Zingiber officinale 56kg, Ziziphus jujuba 56kg.

[0077] ② Processing of medicinal materials: Select and wash Bupleurum, Codonopsis, Licorice, and Scutellaria, then cut them into sections; Select and wash fresh ginger and ginger-processed Pinellia, then coarsely crush them.

[0078] ③ Water extraction: Bupleurum, Scutellaria baicalensis, Codonopsis pilosula, jujube, and licorice are decocted three times with water. The weight ratio of the herbs to water in the first decoction is 1:10, and the weight ratio of the herbs to water in the second and third decoctions is 1:8. Each decoction is 2 hours long. The decoctions are combined and filtered. The filtrate is concentrated under reduced pressure at a vacuum of -0.04 MPa to -0.08 MPa and a temperature of 60 to 90°C until the relative density is 1.10. After standing and cooling, it is filtered to obtain filtrate A.

[0079] ④ Alcohol extraction: Add ginger, Pinellia ternata and fresh ginger to 70% ethanol as solvent and soak for 24 hours. The weight ratio of the soaked medicinal materials to the solvent is 1:6. After soaking, add 70% ethanol for percolation. The weight ratio of the percolated medicinal materials to the added solvent is 1:4. Combine the percolates and filter under reduced pressure at a vacuum of -0.04 MPa to -0.08 MPa and a temperature of 60 to 80°C to recover ethanol until the relative density is 1.10 to obtain filtrate B.

[0080] ⑤ Concentration: Combine filtrate A and filtrate B, and concentrate under reduced pressure at a vacuum of -0.04 MPa to -0.08 MPa and a temperature of 60 to 90°C until the relative density is 1.15. Filter to obtain clear paste C.

[0081] ⑥ Spray drying: The extract C was spray dried with an inlet air temperature of 140℃, an outlet air temperature of 80℃, and a liquid inlet rate of 200mL / min, yielding approximately 100kg of Xiaochaihu granules dry extract powder (with a drying loss of approximately 5%).

[0082] Part Two: Particle Preparation

[0083] The granulation process of the one-step granulation equipment can adopt the "automatic operation" mode. The automatic operation parameters are set as shown in Table 1 below:

[0084] Table 1

[0085]

[0086] ①Prescription composition: 100kg of Xiaochaihu granules dry extract powder, 150kg of sucrose, 150kg of soluble starch, and 1.2kg of orange flavoring (in this embodiment, the weight ratio of sucrose to soluble starch is 1:1, and the weight ratio of excipients to dry extract powder is 3:1).

[0087] ② Raw material processing: sucrose is ground through a 60-mesh sieve, and soluble starch and dry powder are ground together through a 60-mesh sieve to obtain the processed raw and auxiliary materials.

[0088] ③ Preheating: The processed raw and auxiliary materials are fed into the one-step granulation equipment. The airflow distribution plate is a cyclone sintering plate. According to the set "automatic operation" mode parameters, the air inlet volume is 1500M. 3 / h, inlet air temperature 85℃, preheat the material to 50℃, preheating time 10min.

[0089] ④ Granulation: Based on the set "automatic operation" mode parameters, when the material is preheated to 50℃, the air inlet volume is 1500M. 3 The process involves spraying purified water evenly at a flow rate of 4 kg / min, with an inlet air temperature of 85℃, an atomization pressure of 3.0 bar, and a wetting agent flow rate of 4 kg / min for granulation. The granulation time is 10 min, followed by boiling and drying until the moisture content of the dry granules is ≤2.0%. The drying time is 40 min to obtain the dry granules.

[0090] ⑤ The dry granules are passed through a vibrating screen to remove coarse particles above sieve No. 1 and fine powder below sieve No. 5.

[0091] ⑥ General mixing: After sieving, add the dried granules to the orange flavoring and put them into the mixer. Set the speed of the general mixer to 10 rpm and mix for 5 minutes.

[0092] ⑦ Inner packaging: After the granules pass the inspection, they are repackaged using a polyester / aluminum / polyethylene pharmaceutical packaging composite film.

[0093] Example 2

[0094] Part 1: Preparation of Dry Powder

[0095] Same as Example 1.

[0096] Part Two: Particle Preparation

[0097] ①Prescription composition: 100kg of Xiaochaihu granules dry extract powder, 220kg of sucrose, 180kg of soluble starch, and 1.5kg of orange flavoring (in this embodiment, the weight ratio of sucrose to soluble starch is 1.22:1, and the weight ratio of excipients to dry extract powder is 4:1).

[0098] ② Raw material processing: sucrose is ground through a 60-mesh sieve, and soluble starch and dry powder are ground together through a 60-mesh sieve to obtain the processed raw and auxiliary materials.

[0099] ③ Preheating: The processed raw and auxiliary materials are fed into the one-step granulation equipment. The airflow distribution plate is a cyclone sintering plate. According to the set "automatic operation" mode parameters, the air inlet volume is 1500M. 3 / h, inlet air temperature 85℃, preheat the material to 50℃, preheating time 10min.

[0100] ④ Granulation: Based on the set "automatic operation" mode parameters, when the material is preheated to 50℃, the air inlet volume is 1500M. 3 The process involves spraying purified water evenly at a flow rate of 4 kg / min, with an inlet air temperature of 85℃, an atomization pressure of 3.0 bar, and a wetting agent flow rate of 4 kg / min for granulation. The granulation time is 10 min, followed by boiling and drying until the moisture content of the dry granules is ≤2.0%. The drying time is 40 min to obtain the dry granules.

[0101] ⑤ The dry granules are passed through a vibrating screen to remove coarse particles above sieve No. 1 and fine powder below sieve No. 5.

[0102] ⑥ General mixing: After sieving, add the dried granules to the orange flavoring and put them into the mixer. Set the speed of the general mixer to 10 rpm and mix for 5 minutes.

[0103] ⑦ Inner packaging: After the granules pass the inspection, they are repackaged using a polyester / aluminum / polyethylene pharmaceutical packaging composite film.

[0104] Example 3

[0105] Part 1: Preparation of Dry Powder

[0106] Same as Example 1.

[0107] Part Two: Particle Preparation

[0108] ①Prescription composition: 100kg of Xiaochaihu granules dry extract powder, 150kg of sucrose, 150kg of soluble starch, and 1.2kg of orange flavoring (in this embodiment, the weight ratio of sucrose to soluble starch is 1:1, and the weight ratio of excipients to dry extract powder is 3:1).

[0109] ② Raw material processing: sucrose is ground through a 60-mesh sieve, and soluble starch and dry powder are ground together through a 60-mesh sieve to obtain the processed raw and auxiliary materials.

[0110] ③ Preheating: The processed raw and auxiliary materials are fed into the one-step granulation equipment. The airflow distribution plate is a cyclone sintering plate. According to the set "automatic operation" mode parameters, the air inlet volume is 1200M. 3 / h, inlet air temperature 90℃, preheat the material to 50℃, preheating time 10min.

[0111] ④ Granulation: Based on the set "automatic operation" mode parameters, when the material is preheated to 50℃, the air inlet volume is 1200M. 3 The process involves spraying purified water evenly at a flow rate of 3 kg / min, with an inlet air temperature of 90℃, an atomization pressure of 2.0 bar, and a wetting agent flow rate of 3 kg / min. Granulation is carried out for 13 min, followed by boiling and drying until the moisture content of the dry granules is ≤2.0%. The drying time is 50 min to obtain the dry granules.

[0112] ⑤ The dry granules are passed through a vibrating screen to remove coarse particles above sieve No. 1 and fine powder below sieve No. 5.

[0113] ⑥ General mixing: After sieving, add the dried granules to the orange flavoring and put them into the mixer. Set the speed of the general mixer to 10 rpm and mix for 5 minutes.

[0114] ⑦ Inner packaging: After the granules pass the inspection, they are repackaged using a polyester / aluminum / polyethylene pharmaceutical packaging composite film.

[0115] Comparative Example 1

[0116] Part 1: Preparation of Dry Powder

[0117] Same as Example 1.

[0118] Part Two: Particle Preparation

[0119] ①Prescription composition: 200kg of Xiaochaihu granules dry extract powder, 130kg of sucrose, 70kg of soluble starch, and 1.2kg of orange flavoring (in this comparative example, the weight ratio of sucrose to soluble starch is 1.86:1, and the weight ratio of excipients to dry extract powder is 1:1).

[0120] ② Raw material processing: sucrose is ground through a 60-mesh sieve, and soluble starch and dry powder are ground together through a 60-mesh sieve to obtain the processed raw and auxiliary materials.

[0121] ③ Preheating: The processed raw and auxiliary materials are fed into the one-step granulation equipment. The airflow distribution plate is a cyclone sintering plate. According to the set "automatic operation" mode parameters, the air inlet volume is 1500M. 3 / h, inlet air temperature 85℃, preheat the material to 50℃, preheating time 10min.

[0122] ④ Granulation: Based on the set "automatic operation" mode parameters, when the material is preheated to 50℃, the air inlet volume is 1500M. 3The process involves spraying purified water evenly at a flow rate of 4 kg / min, with an inlet air temperature of 85℃, an atomization pressure of 3.0 bar, and a wetting agent flow rate of 4 kg / min for granulation. The granulation time is 10 min, followed by boiling and drying until the moisture content of the dry granules is ≤2.0%. The drying time is 40 min to obtain the dry granules.

[0123] ⑤ The dry granules are passed through a vibrating screen to remove coarse particles above sieve No. 1 and fine powder below sieve No. 5.

[0124] ⑥ General mixing: After sieving, add the dried granules to the orange flavoring and put them into the mixer. Set the speed of the general mixer to 10 rpm and mix for 5 minutes.

[0125] ⑦ Inner packaging: After the granules pass the inspection, they are repackaged using a polyester / aluminum / polyethylene pharmaceutical packaging composite film.

[0126] Example 4

[0127] Part 1: Preparation of Dry Powder

[0128] Same as Example 1.

[0129] Part Two: Particle Preparation

[0130] ①Prescription composition: 100kg of Xiaochaihu granules dry extract powder, 150kg of sucrose, 150kg of soluble starch, and 1.2kg of orange flavoring (in this embodiment, the weight ratio of sucrose to soluble starch is 1:1, and the weight ratio of excipients to dry extract powder is 3:1).

[0131] ② Raw material processing: sucrose is ground through a 60-mesh sieve, and soluble starch and dry powder are ground together through a 60-mesh sieve to obtain the processed raw and auxiliary materials.

[0132] ③ Preheating: The processed raw and auxiliary materials are fed into the one-step granulation equipment. The airflow distribution plate is a cyclone sintering plate, and the inlet air volume is set to 1500M. 3 / h, inlet air temperature 65℃, preheat material to 50℃, preheating time 20min.

[0133] ④ Granulation: When the material is preheated to 50℃, set the air inlet volume to 1500M. 3 The process involves spraying purified water evenly at a flow rate of 4 kg / min, with an inlet air temperature of 65℃, an atomization pressure of 3.0 bar, and a wetting agent flow rate of 4 kg / min for granulation. The granulation time is 10 min, followed by boiling and drying until the moisture content of the dry granules is ≤2.0%. The drying time is 60 min to obtain the dry granules.

[0134] ⑤ The dry granules are passed through a vibrating screen to remove coarse particles above sieve No. 1 and fine powder below sieve No. 5.

[0135] ⑥ General mixing: After sieving, add the dried granules to the orange flavoring and put them into the mixer. Set the speed of the general mixer to 10 rpm and mix for 5 minutes.

[0136] ⑦ Inner packaging: After the granules pass the inspection, they are repackaged using a polyester / aluminum / polyethylene pharmaceutical packaging composite film.

[0137] Example 5

[0138] Part 1: Preparation of Dry Powder

[0139] Same as Example 1.

[0140] Part Two: Particle Preparation

[0141] ①Prescription composition: 100kg of Xiaochaihu granules dry extract powder, 150kg of sucrose, 150kg of soluble starch, and 1.2kg of orange flavoring (in this embodiment, the weight ratio of sucrose to soluble starch is 1:1, and the weight ratio of excipients to dry extract powder is 3:1).

[0142] ② Raw material processing: sucrose is ground through a 60-mesh sieve, and soluble starch and dry powder are ground together through a 60-mesh sieve to obtain the processed raw and auxiliary materials.

[0143] ③ Preheating: The processed raw and auxiliary materials are fed into the one-step granulation equipment. The airflow distribution plate is a cyclone sintering plate. According to the set "automatic operation" mode parameters, the air inlet volume is 1500M. 3 / h, inlet air temperature 85℃, preheat the material to 50℃, preheating time 10min.

[0144] ④ Granulation: Based on the set "automatic operation" mode parameters, when the material is preheated to 50℃, the air inlet volume is 1500M. 3 The process involves spraying purified water evenly at a flow rate of 1 kg / min, with an inlet air temperature of 85℃, an atomization pressure of 1.0 bar, and a wetting agent flow rate of 1 kg / min. Granulation is carried out for 40 min, followed by boiling and drying until the moisture content of the dry granules is ≤2.0%. The drying time is 40 min to obtain the dry granules.

[0145] ⑤ The dry granules are passed through a vibrating screen to remove coarse particles above sieve No. 1 and fine powder below sieve No. 5.

[0146] ⑥ General mixing: After sieving, add the dried granules to the orange flavoring and put them into the mixer. Set the speed of the general mixer to 10 rpm and mix for 5 minutes.

[0147] ⑦ Packaging: After the granules pass the inspection, they are repackaged using a polyester / aluminum / polyethylene pharmaceutical packaging composite film.

[0148] The quality of the samples prepared in the above examples and comparative examples was tested, including taste, particle shape, particle yield, and component content.

[0149] Taste: taste and smell.

[0150] Particle characteristics: visual inspection.

[0151] Granule yield: Granule yield = Total weight of dry granules after granulation (kg) ÷ [Weight of dry extract of Xiaochaihu granules (kg) × (1 - Moisture content of dry extract (%)) + Weight of sucrose (kg) + Weight of soluble starch (kg) + Weight of orange flavoring (kg)] × 100%.

[0152] Detection of baicalin and glycyrrhizic acid content:

[0153] Determined by high performance liquid chromatography (General Chapter 0512, Part IV, Chinese Pharmacopoeia 2020 Edition).

[0154] Chromatographic conditions and system suitability tests were performed using octadecylsilane-bonded silica gel as the packing material (column length 250 mm, inner diameter 4.6 mm, particle size 5 μm); acetonitrile was used as mobile phase A, and 0.2% phosphoric acid solution was used as mobile phase B, with gradient elution performed according to the specifications in Table 2; detection wavelengths were 315 nm (for baicalin detection) and 252 nm (for glycyrrhizic acid detection); column temperature was 25 °C; flow rate was 0.8 mL / min. The theoretical plate number, calculated based on the baicalin peak, should not be less than 10,000.

[0155] Table 2

[0156]

[0157] Preparation of reference solution: Take appropriate amounts of baicalin and ammonium glycyrrhizate reference standards, accurately weigh them, and add 70% ethanol to prepare a mixed solution containing 250 μg of baicalin and 40 μg of ammonium glycyrrhizate per 1 ml, which is the result of (weight of glycyrrhizic acid = weight of ammonium glycyrrhizate / 1.0207).

[0158] Preparation of the test solution: Take this product, mix well, take an appropriate amount, grind finely, take about 0.75g, accurately weigh, place in a stoppered conical flask, accurately add 10ml of 70% ethanol, stopper tightly, weigh, sonicate (power 250W, frequency 50kHz) for 30 minutes, cool, weigh again, make up the lost weight with 70% ethanol, shake well, filter, and take the filtrate to obtain the test solution.

[0159] The assay involves precisely pipetting 10 μl each of the reference solution and the test solution into a liquid chromatograph and measuring the results.

[0160] The results are entered into Table 3:

[0161] Table 3

[0162]

[0163]

[0164] As shown in Table 3, the Xiaochaihu granules of the present invention (Examples 1-5) are uniform in size, have a high yield, good taste, and good repeatability. In particular, the preparation methods of Examples 1-3 are easier to granulate and can greatly improve the uniformity and yield of granules. At the same time, the RSD between the test results is lower, indicating that the preparation process has high precision and better repeatability.

[0165] Compared to Example 1, in Example 4, the granulation equipment was set to a lower inlet air temperature (65°C) during the preparation of Xiaochaihu granules. This resulted in an increase in coarse particles, a decrease in particle yield, a slight decrease in the content of baicalin and glycyrrhizic acid, and poorer reproducibility of the preparation process. This indicates that the inlet air temperature affects the particle characteristics, yield, and component content of the Xiaochaihu granules prepared by this invention. Setting the inlet air temperature of the granulation equipment to 70°C-100°C is more conducive to the preparation of Xiaochaihu granules of this invention and improves the quality of the Xiaochaihu granules.

[0166] Compared to Example 1, in Example 5, the atomization pressure was too low (1.0 bar) during the preparation of Xiaochaihu granules, resulting in finer granules, more fine powder, a lower granule yield, a slight decrease in the content of baicalin and glycyrrhizic acid, and poorer reproducibility of the preparation process. This indicates that the atomization pressure during granulation significantly affects the granule properties and yield of the prepared Xiaochaihu granules, and the preferred atomization pressure is 2.0 bar to 4.0 bar.

[0167] Compared to Example 1, in Comparative Example 1, the weight ratio of sucrose to soluble starch in the raw materials for preparing Xiaochaihu granules was too high (1.86:1), and the weight ratio of excipients to dry extract powder was too low (1:1). This resulted in a reduced granule texture, material stickiness and clumping during granulation, making granulation difficult, significantly reducing granule yield, and noticeably worse repeatability of the preparation process. This indicates that the ratio of raw materials used in the preparation of Xiaochaihu granules in this invention has a very important impact on the texture, granule quality, and ease of granulation of the prepared Xiaochaihu granules. Preferably, the weight ratio of the total weight of sucrose to soluble starch to the weight of the dry extract powder is (2-5):1, and the weight ratio of sucrose to soluble starch is 1:1.5-1.5:1, which ensures easy granulation, uniform granules, high granule yield, and good granulation repeatability.

[0168] Example 6

[0169] Part 1: Prescription Composition Screening

[0170] In the following studies, particle granulation was performed according to the preparation method described in Example 1.

[0171] ① Survey of commonly used diluents for granules

[0172] Commonly used diluents for granules include sucrose, dextrin, mannitol, soluble starch, and lactose. The advantages and disadvantages of each diluent were compared, and a preliminary screening of diluents was conducted for formulation consideration. See Table 4 below for details.

[0173] Table 4

[0174]

[0175]

[0176] Based on their own experience, combined with the common diluents for granules and the characteristics of this product for children, the inventors found that mannitol has a potential diarrheal effect in children, lactose has lactose intolerance issues, and microcrystalline cellulose is commonly used in suspension granules. They further selected sucrose, dextrin, soluble starch, and corn starch for formulation screening and investigation.

[0177] ② Comparison of granulation effects of different excipients

[0178] To investigate the effects of using different excipients alone and in combination with dry extract powder on granulation, quantitative amounts of different excipients and dry extract powder were ground to 60 mesh and then subjected to one-step granulation. Granule yield, granule characteristics, solubility, and taste were used as evaluation indicators, as detailed in Table 5 below:

[0179] Table 5

[0180]

[0181] With an excipient to dry powder weight ratio of 5:1, sucrose exhibits good granulation properties, producing uniform granules and also functioning as a flavoring agent. Soluble starch, corn starch, and dextrin produce fine granules, but there is room for further reduction in excipient usage, resulting in poorer taste. Considering the above, to reduce excipient usage while ensuring granule shape and taste, it is preferable to use sucrose in combination with other excipients for formulation evaluation.

[0182] ③ Comparison of granulation effects with different excipient combinations

[0183] To investigate the effects of sucrose combined with different excipients and dry extract powder on granulation, sucrose was used in combination with different excipients as a diluent. The sucrose was ground to 60 mesh, and the soluble starch (or corn starch or dextrin) and dry extract powder were ground to 60 mesh and then granulated separately in one step. Granulation yield, granule characteristics, solubility, and taste were used as evaluation indicators, as detailed in Table 6 below:

[0184] Table 6

[0185]

[0186] Under the premise that the weight ratio of excipients to dry powder is 5:1, all three combination schemes can be granulated. Among them, sucrose combined with dextrin produces more fine powder. When examining solubility and taste, sucrose combined with corn starch has poor solubility, and sucrose combined with dextrin has a slightly astringent taste. The preferred combination is sucrose combined with soluble starch for formulation evaluation.

[0187] ④ Comparison of granulation effects with different proportions of excipients

[0188] To investigate the effect of different ratios of sucrose and soluble starch on granulation, different ratios of sucrose and soluble starch were used as excipients. The sucrose was ground to 60 mesh, and the soluble starch and dry extract powder were ground to 60 mesh and then granulated separately in one step. Granulation yield, granule characteristics, solubility, and taste were used as evaluation indicators, as detailed in Table 7 below:

[0189] Table 7

[0190]

[0191] Under the premise that the weight ratio of excipients to dry powder is 5:1, granulation can be carried out with sucrose:soluble starch ratios of 2:1, 1.5:1, 1:1, 1:1.5, and 1:2. Among these, when the sucrose content is high (2:1), the material becomes sticky during granulation, with more coarse particles and a lower yield. When the soluble starch content is high (1:2), the granules are loose and brittle, with more fine powder and a lower yield. The preferred weight ratio of sucrose to soluble starch is 1:1.5-1.5:1, with a weight ratio of 1:1 being the best, resulting in a high granule yield and meeting the requirements for solubility and taste.

[0192] ⑤ Comparison of granulation effects with different proportions of excipient dry powder

[0193] To investigate the effect of different ratios of excipients and dry extract on granulation, one-step granulation was performed using different ratios of excipients and extract. Granulation yield, granule characteristics, solubility, and mouthfeel were used as evaluation indicators, as detailed in Table 8 below:

[0194] Table 8

[0195]

[0196] Under the premise that the weight ratio of sucrose to soluble starch is 1:1, the ratio of excipient to dry extract powder can be 5:1, 4:1, 3:1, 2:1, and 1:1 for granulation. When the proportion of dry extract powder is relatively high (1:1), the material will stick during granulation, resulting in more coarse particles and a lower yield. The preferred weight ratio of excipient to dry extract powder is 5:1-2:1, with a weight ratio of 3:1 being the best. This results in a high granule yield, low excipient usage, and satisfactory solubility and taste.

[0197] Part Two: Selection of Airflow Distribution Plate

[0198] To investigate the effect of airflow distribution plates on granulation, tests were conducted using different airflow distribution plates, with particle yield and particle properties used as evaluation indicators. See Table 9 below for details:

[0199] Table 9

[0200]

[0201] Under the premise that the amount of auxiliary materials and dry powder is the same, the use of cyclone sintering plate can more effectively fluidize the material and achieve better granulation effect. At the same time, it can reduce the loss of fine powder through the airflow distribution plate and further improve the particle yield. The cyclone sintering plate is preferred for the airflow distribution plate.

[0202] Part Three: Investigation of Key Process Parameters

[0203] The formulation described in Example 1 was used for granulation in the following studies.

[0204] ① Comparison of granulation effects at different inlet air temperatures

[0205] To investigate the effect of different inlet air temperatures on granulation, the same formulation material was used, and one-step granulation was performed with different inlet air temperatures. Granule yield, granule properties, drying time, and content were used as evaluation indicators, as detailed in Table 10 below:

[0206] Table 10

[0207]

[0208] Granulation at various inlet air temperatures showed no significant difference in particle content, indicating that inlet air temperature had a relatively small impact on the content. However, at lower inlet air temperatures (60℃), the material exhibited stickiness during granulation, resulting in more coarse particles and a decreased yield. At higher inlet air temperatures (100℃), the wetting agent dried too quickly during granulation, failing to fully wet the material and resulting in more fine powder particles. Furthermore, higher inlet air temperatures led to shorter drying times. An inlet air temperature of 70-100℃, with 80-90℃ being optimal, resulted in uniform particle size, high yield, and shorter drying time, simultaneously improving both production efficiency and product quality.

[0209] ② Comparison of granulation effects at different material temperatures

[0210] To investigate the effect of different material temperatures on granulation, the same formulation materials were used, and one-step granulation was performed using different material temperatures. Granule yield, granule properties, moisture content, and other parameters were used as evaluation indicators, as detailed in Table 11 below:

[0211] Table 11

[0212]

[0213] Granulation at various material temperatures showed no significant differences in particle moisture content. However, at lower material temperatures (40-45℃), the material exhibited stickiness during granulation, resulting in more coarse particles; at higher material temperatures (55-60℃), the wetting agent dried faster during granulation, failing to fully wet the material, leading to more fine powder particles. The preferred material temperature was 45-55℃, with 50℃ being a suitable material temperature for both preheating and granulation spray initiation.

[0214] ③ Comparison of granulation effects under different atomization pressures

[0215] To investigate the effect of different atomization pressures on granulation, the same formulation materials were used, and one-step granulation was performed under different atomization pressures. Granule yield, granule properties, moisture content, and other parameters were used as evaluation indicators, as detailed in Table 12 below:

[0216] Table 12

[0217]

[0218] Granulation at various atomization pressures showed no significant differences in particle moisture content. However, at lower atomization pressures (1.0 bar), the granulation droplets were larger, causing material adhesion and agglomeration, resulting in "bed collapse." At higher atomization pressures (5.0 bar), the granulation droplets were smaller, leading to faster drying, insufficient wetting of the material, finer particles, and a decrease in yield. The optimal atomization pressure range was 2.0 bar to 4.0 bar, resulting in good atomization, uniform particles, and a high yield.

[0219] ④ Comparison of granulation effects of different wetting agents

[0220] To investigate the effect of different wetting agents on granulation, the same formulation materials were used, and one-step granulation was carried out using different wetting agents. Granule yield, granule properties, drying time, and content were used as evaluation indicators, as detailed in Table 13 below:

[0221] Table 13

[0222]

[0223] Granulation with different wetting agents showed no significant difference in particle content. However, at higher ethanol concentrations (50% ethanol), the wetting agent dried faster, failing to fully wet the material, resulting in finer particles and a lower yield. Using purified water as the preferred wetting agent can improve the yield, reduce the use of organic solvents, and enhance the ease of production operations.

[0224] ⑤ Comparison of different total mixing times

[0225] To investigate the effect of different total mixing times on product quality, the same formulation materials were granulated and then subjected to total mixing to examine the mixing uniformity. See Table 14 below for details:

[0226] Table 14

[0227]

[0228] The particle mixing uniformity was good at different total mixing times (3, 5, 10 minutes), with no obvious differences observed. The preferred total mixing time is 3-10 minutes to ensure the mixing effect.

[0229] ⑥ Comparison of Optimal Processes

[0230] The parameters affecting the one-step granulation effect of this invention are summarized in Table 15 below:

[0231] Table 15

[0232]

[0233]

[0234] As shown in Table 15 above, multiple continuous parameters jointly affect the one-step granulation effect of the present invention. The preferred main technical parameters are: air inlet temperature 80-90℃, spray (granulation) atomization pressure 2.0 bar-3.0 bar, material temperature control 45℃-55℃ (preheating endpoint temperature 50℃), and purified water as wetting agent, which can ensure easy granulation and make the obtained Xiaochaihu granules uniform and with a higher yield.

[0235] Comparison of the one-step granulation preparation method of the present invention with the existing wet granulation combined with fluidized bed drying granulation (Table 16):

[0236] Table 16

[0237]

[0238] In summary, the present invention's Xiaochaihu granules first optimize the formula by drying the extract obtained from the active ingredients of traditional Chinese medicine raw materials into a dry powder, then compounding it with suitable excipients sucrose and soluble starch, and further controlling the total amount of the dry powder and excipients, as well as the ratio of sucrose and soluble starch, to obtain the preparation formula for the Xiaochaihu granules. The addition of an appropriate amount of flavoring not only acts as a flavoring agent to enhance the taste of the medicine, but also, together with sucrose and soluble starch, acts as an excipient compounded with the active ingredient dry powder. Together, these three elements further ensure the quality of the subsequent granulation of the dry powder, resulting in Xiaochaihu granules that are uniform, compact, and have good solubility.

[0239] This invention further optimizes the preparation method of Xiaochaihu granules. The preparation method described in this invention enables one-step granulation, continuous, and automated production of Xiaochaihu granules. Through continuous control of multiple key related parameters, the preparation method of this invention results in Xiaochaihu granules with high yield, uniform particle size, suitable density, narrow particle size distribution, and good repeatability between different batches.

[0240] This invention, through further improvements in both the formulation and preparation method, results in Xiaochaihu granules with uniform particle size and good formability. It also improves medication adherence in children while effectively reducing the risk of inactive excipient intake and excessive sucrose intake in children during clinical medication use, thus increasing safety. The Xiaochaihu granules possess antipyretic, anti-inflammatory, analgesic, and gastrointestinal regulating effects, making them highly suitable for treating diseases including childhood gastroenteritis.

[0241] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0242] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A type of Xiaochaihu granules, characterized in that, The Xiaochaihu granules are prepared from a dry extract of traditional Chinese medicine, sucrose, soluble starch and flavoring as raw materials; the total weight ratio of sucrose and soluble starch to the weight ratio of the dry extract of traditional Chinese medicine is (2-5):1, the weight ratio of sucrose to soluble starch is 1:1.5-1.5:1, and the weight ratio of flavoring to the dry extract of traditional Chinese medicine is (0-5):(100-500). The herbal composition dry powder is prepared by extracting the active ingredients and then drying the resulting clear paste. The active ingredients are extracted from the following raw materials in parts by weight: Bupleurum chinense 100-200 parts, Scutellaria baicalensis 40-70 parts, Pinellia ternata 40-70 parts, Codonopsis pilosula 40-70 parts, fresh ginger 40-70 parts, licorice root 40-70 parts, and jujube 40-70 parts.

2. The Xiaochaihu granules as described in claim 1, characterized in that, The total weight ratio of the sucrose and soluble starch to the weight ratio of the dry extract powder of the traditional Chinese medicine composition is (3-4):1; and / or, The weight ratio of sucrose to soluble starch is 1:1.5 to 1:1; and / or, The weight ratio of the fragrance to the dry powder of the traditional Chinese medicine composition is (1-5):(100-500), preferably (1-2):(100-300); more preferably (1-2):(100-200).

3. The Xiaochaihu granules as described in claim 1 or 2, characterized in that, The active ingredients are extracted from the following raw materials in parts by weight: Bupleurum chinense 150-200 parts, Scutellaria baicalensis 56-70 parts, Pinellia ternata 56-70 parts, Codonopsis pilosula 56-70 parts, fresh ginger 56-70 parts, licorice 56-70 parts, and jujube 56-70 parts; preferably, the active ingredients of the dry extract powder of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: Bupleurum chinense 150±5 parts, Scutellaria baicalensis 56±5 parts, Pinellia ternata 56±5 parts, Codonopsis pilosula ±5 parts, fresh ginger 56±5 parts, licorice 56±5 parts, and jujube 56±5 parts.

4. The Xiaochaihu granules as described in claim 1 or 2, characterized in that, The Xiaochaihu granules are prepared from the following raw materials: a dry extract of traditional Chinese medicine composition, sucrose, soluble starch, and flavoring. The sucrose, the dry extract of traditional Chinese medicine composition, and the soluble starch are fed into a one-step granulation device, and the air inlet temperature is set to 70℃-100℃ for preheating. A wetting agent is sprayed in for atomized granulation, followed by drying, sieving, adding flavoring, and mixing to obtain the Xiaochaihu granules.

5. The Xiaochaihu granules as described in claim 4, characterized in that, Preheat to 40℃-60℃, preferably 45℃-55℃.

6. The Xiaochaihu granules as described in claim 4 or 5, characterized in that, The atomization pressure is 2.0 bar to 4.0 bar, preferably 2.0 bar to 3.0 bar.

7. The method for preparing Xiaochaihu granules according to any one of claims 1 to 6, characterized in that, Includes the following steps: ① Preheating: Take the sucrose, the dry extract powder of the traditional Chinese medicine composition and the soluble starch, put them into the one-step granulation equipment, control the boiling fluidization of the materials, and preheat the materials; ② Granulation: After the material is preheated, control the material to boil and fluidize, and spray the wetting agent evenly for atomization granulation. After granulation, dry to obtain dry granules. ③ Screening: The dry particles are screened by a vibrating screener; ④Total mixing: Add flavoring to the dry granules obtained by sieving and mix to obtain the Xiaochaihu granules.

8. The preparation method according to claim 7, characterized in that, The air inlet temperature of the granulation equipment is set to 70℃-100℃, preferably 80℃-90℃.

9. The preparation method according to claim 7 or 8, characterized in that, In step ①, the material is preheated to 40℃-60℃, preferably 45℃-55℃.

10. The preparation method according to claim 9, characterized in that, In step ②, the atomization pressure is 2.0 bar to 4.0 bar, preferably 2.0 bar to 3.0 bar.

11. The preparation method according to claim 7, characterized in that, The wetting agent mentioned in step ② is selected from water or ethanol with a concentration not exceeding 30%; preferably, the wetting agent is water.

12. The preparation method according to any one of claims 7 to 11, characterized in that, The airflow distribution plate of the granulation equipment is a cyclone sintering plate; and / or... The air inlet volume of the granulation equipment is set to 1000 m³ / h. 3 / h-2000M 3 / h; and / or, The flow rate of the wetting agent in step ② is 2 kg / min-6 kg / min; and / or the granulation time is 5 min-15 min; and / or the drying is fluidized bed drying.

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