Pediatric xiao chai hu granule and preparation method thereof

Abstract

The invention provides a common goldenrop granule for children and a preparation method thereof. The common goldenrop granule is prepared from the following raw materials: traditional Chinese medicine composition dry paste powder, cane sugar, soluble starch and essence, the ratio of the total weight of the cane sugar and the soluble starch to the weight of the traditional Chinese medicine composition dry paste powder is (2-5): 1, the weight ratio of the cane sugar to the soluble starch is (1: 1.5)-(1.5: 1), and the weight ratio of the essence to the traditional Chinese medicine composition dry paste powder is (0-5): (100-500); the dry paste powder of the traditional Chinese medicine composition is prepared by extracting active ingredients of raw materials to obtain clear paste and then drying the clear paste. According to the common goldenrop granules disclosed by the invention, by optimizing a formula, after the total amount of auxiliary materials and the dosage of cane sugar are greatly reduced, a good taste can be kept, meanwhile, the prepared common goldenrop granules are uniform and proper in looseness, and the medication compliance and safety of children can be improved; and the risk of inactive auxiliary material intake during clinical medication of child patients and excessive sucrose intake of child groups in a development period are reduced.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202411997447.0 (22) Application Date 2024.12.31 (71) Applicant Guangzhou Baiyunshan Guanghua Pharmaceutical Co., Ltd. Address 510285 No. 1, Nanshi Road, Haizhu District, Guangzhou City, Guangdong Province (72) Inventors Zeng Chengfang, Bi Cong, Zhang Junhua, Liang Xiaowen, He Min'er, Situ Wenhui, Du Haiyong (74) Patent Agency Guangzhou Guangdian Intellectual Property Agency (General Partnership) 44365 Patent Attorney Tuo Jiuling, Wan Zhixiang (51) Int.Cl. A61K 36 / 9068 (2006.01) A61K 9 / 16 (2006.01) A61K 47 / 26 (2006.01) A61K 47 / 36 (2006.01) A61P 11 / 00 (2006.01) A61P 29 / 00 (2006.01) A61P 31 / 12 (2006.01) A61P 1 / 14 (2006.01) A61P 1 / 00 ​​(2006.01) A61P 37 / 04 (2006.01) (54) Invention Title: A Child-Friendly Xiao Chai Hu Granule and Its Preparation Method (57) Abstract: This invention provides a child-friendly Xiao Chai Hu granule and its preparation method. The Xiao Chai Hu granule is prepared from a traditional Chinese medicine composition dry extract powder, 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 traditional Chinese medicine composition dry extract powder is (2-5):1, and the weight ratio of sucrose to soluble starch is 1:1.5-1. The weight ratio of the fragrance 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 paste. Through formula optimization, the Xiaochaihu granules of this invention maintain a good taste while significantly reducing the total amount of excipients and sucrose. Simultaneously, it ensures that the prepared Xiaochaihu granules are uniform in size and appropriately firm. Furthermore, it improves medication adherence and safety in children, reducing the risk of inactive excipient intake and excessive sucrose intake in children during clinical medication use. Claims 2 pages, Description 18 pages, CN 122297626 A 2026.06.30 CN 1 22 29 76 26 A 1. A Xiaochaihu granule, characterized in that the Xiaochaihu granule is 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 flavoring and the traditional Chinese medicine composition...The weight ratio of the dry extract powder of the herbal composition is (0-5):(100-500); the dry extract powder of the herbal composition is prepared by extracting the active ingredients and then drying the resulting extract. 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 dry extract powder of the traditional Chinese medicine composition is (3-4):1; and / or, the weight ratio of the sucrose to the soluble starch is 1:1.5-1:1; and / or, the weight ratio of the flavoring to the dry extract 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 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 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 Xiao Chai Hu granules as described in claim 1 or 2, characterized in that the Xiao Chai Hu granules are prepared from a traditional Chinese medicine composition dry extract powder, sucrose, soluble starch, and flavoring as raw materials according to the following method: the sucrose, the traditional Chinese medicine composition dry extract powder, and the soluble starch are fed into a one-step granulation device, and the inlet air temperature is set to 70℃-100℃ for preheating; a wetting agent is sprayed in for atomized granulation, drying, sieving, adding flavoring, and mixing to obtain the Xiao Chai Hu granules. 5. The Xiao Chai Hu granules as described in claim 4, characterized in that the preheating temperature is 40℃-60℃, preferably 45℃-55℃. 6. The Xiao Chai Hu granules as described in claim 4 or 5, characterized in that the atomization pressure is 2.0 bar-4.0 bar, preferably 2.0 bar-3.0 bar. 7. The method for preparing Xiaochaihu granules according to any one of claims 1 to 6, characterized in that it includes the following steps: ① Preheating: taking the sucrose, the dry extract powder of the traditional Chinese medicine composition and soluble starch, and putting them into a one-step granulation device, controlling the boiling fluidization of the materials to preheat the materials; ② Granulation: after the materials are preheated, controlling the boiling fluidization of the materials, uniformly spraying a wetting agent for atomized granulation, and drying after granulation to obtain dry granules; ③ Sieving: the dry granules are sieved through a vibrating sieve.④ Total Mixing: Add flavoring to the dry granules obtained by sieving, mix, and the Xiaochaihu granules are obtained. 8. The preparation method according to claim 7, characterized in that the inlet air 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 the atomization pressure in step ② is 2.0 bar-4.0 bar, preferably 2.0 bar-3.0 bar. 11. The preparation method according to claim 7, characterized in that the wetting agent in step ② is selected from water or ethanol with a concentration not exceeding 30%; preferably, the wetting agent is water. Claims 1 / 2 Page 2 CN 122297626 A 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 flow rate of the granulation equipment is set to 1000M3 / h-2000M3 / h; and / or, the flow rate of the wetting agent in step ② is 2kg / min-6kg / min; and / or, the granulation time is 5min-15min; and / or, the drying is boiling drying. Claims 2 / 2 Page 3 CN 122297626 A Pediatric Xiaochaihu Granules and Their Preparation Method Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a pediatric Xiaochaihu granules and their preparation method. Background Art

[0002] Xiaochaihu granules are a traditional Chinese medicine preparation developed based on the famous prescription Xiaochaihu Decoction in "Treatise on Febrile Diseases" written by Zhang Zhongjing, the Sage of Medicine, combined with modern Chinese medicine extraction and preparation technology. The original formula, Xiao Chai Hu Tang, is summarized by traditional Chinese medicine as follows: Xiao Chai Hu Tang has a harmonizing effect, with Pinellia, Ginseng, and Licorice as adjuncts; with the addition of 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, which are composed of Bupleurum, Scutellaria, Ginger-processed Pinellia, Codonopsis, Ginger, Licorice, Jujube, and other medicinal materials. Thanks to its scientific and reasonable combination structure, it can relieve exterior heat, soothe the liver and harmonize the stomach, and is used for exogenous diseases, Shao Yang syndrome, with symptoms such as 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 prescription that is frequently used in clinical practice, and its application range is extremely wide. Xiao Chai Hu Granules, inherited from this formula, have become a widely used and highly praised cold and fever medicine among ordinary people in my country today. In addition to treating colds and fevers, Xiao Chai Hu Granules also have antiviral, spleen and stomach regulating, and immune function enhancement effects, and have broad clinical application prospects.

[0004] However, as a traditional Chinese medicine formula, there are currently no Xiao Chai Hu Granules available on the market specifically for children.Dosage form. Pediatric medicines refer to medicines specifically for minors under the age of 14. Currently, the excipients used in commercially available Xiaochaihu granules are divided into three categories: the first category is sucrose, which can easily cause tooth decay in children if used frequently in large doses; the second category is lactose, as some children are lactose intolerant; the third category is dextrin, mannitol, and other excipients. Mannitol has a potential laxative effect in children. The above excipients are not suitable for children in the developmental stage to ingest too much.

[0005] In addition, the current preparation method of Chinese medicine granules mostly uses wet granulation of Chinese medicine extract followed by boiling and drying. This preparation method is mainly based on manual operation control and subjective judgment of the soft material state. It has high operational adaptability but poor stability, and has problems such as difficulty in granulation and drying, uneven particle size, large content differences, and the need to use high-concentration ethanol to assist in granulation.

[0006] Therefore, it is necessary to develop a pediatric Xiaochaihu granule that meets the characteristics of children's medication, and to improve the granule production process, simplify production operations, and improve the quality, efficiency, and stability of granule production.

[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 the compliance and safety of children's medication.

[0008] In a first aspect, the present invention provides a small bupleurum granule, wherein the small bupleurum granule is 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);

[0009] The dry extract powder of the traditional Chinese medicine composition is prepared by extracting the active ingredients and then drying the resulting extract, wherein the active ingredients are extracted from the following raw materials in parts by weight: 100-200 parts of Bupleurum chinense, 40-70 parts of Scutellaria baicalensis, 40-70 parts of Pinellia ternata, 40-70 parts of Codonopsis pilosula, 40-70 parts of fresh ginger, 40-70 parts of licorice, and 40-70 parts of jujube. Instructions for Use, Page 1 / 18, CN 122297626 A

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

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

[0012] In some embodiments, the weight ratio of the flavoring to the dry extract powder of the traditional Chinese medicine composition is (1-5):(100-500), more preferably (1-2):(100-300); 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 a traditional Chinese medicine composition dry extract powder, sucrose, soluble starch, and flavoring as raw materials according to the following method: the sucrose, the traditional Chinese medicine composition dry extract powder, and the soluble starch are fed into a one-step granulation device, and the inlet air temperature is set to 70℃-100℃ for preheating; a wetting agent is sprayed in for atomization granulation, drying, sieving, adding flavoring, and mixing to obtain the Xiaochaihu granules.

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

[0016] In some embodiments, the preheating is set to 40℃-60℃, preferably 45℃-55℃.

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

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

[0019] ① Preheating: taking the sucrose, the dry extract powder of the traditional Chinese medicine composition and soluble starch, and putting them into a one-step granulation device, controlling the boiling fluidization of the materials, and preheating the materials;

[0020] ② Granulation: after the materials are preheated, controlling the boiling fluidization of the materials, uniformly spraying a wetting agent for atomized granulation, and drying after granulation to obtain dry granules;

[0021] ③ Sieving: the dry granules are passed through a vibrating sieve;

[0022] ④ Mixing: adding fragrance to the sieved dry granules and mixing to obtain the Xiaochaihu granules.

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

[0024] In some embodiments, in step ①, the materials are preheated to 40℃-60℃, preferably 45℃-55℃.

[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 to 2000 m³ / h.

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

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

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

[0032] This invention provides a Xiaochaihu granule that is very suitable for pediatric patients. Considering that children should not ingest too many excipients and have a need for good taste, this invention has conducted extensive research on the formulation. The clear extract obtained after extracting active ingredients from traditional Chinese medicine raw materials is dried into a dry powder, and suitable excipients sucrose and soluble starch are compounded. The total amount of the dry powder and excipients, as well as the ratio of sucrose and soluble starch, are further optimized to obtain the preparation formula of the Xiaochaihu granule (see page 2 / 18 of the instruction manual, CN 122297626 A). In the formula, adding an appropriate amount of flavoring can not only act as a flavoring agent to enhance the taste of the medicine, but also, together with sucrose and soluble starch, serve as excipients and are compounded with the active ingredient dry extract powder. Together, these three ingredients can 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] At the same time, the present invention also optimizes the preparation method of Xiaochaihu granules. The preparation method described in the present invention can realize one-step granulation, continuous, and automated production of Xiaochaihu granules. In the raw materials for preparing Xiaochaihu granules of the present invention, dry extract powder is used 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 can realize automatic feeding and continuous production. Moreover, the raw materials for preparing Xiaochaihu granules after the formula optimization are simple. After adding the dry extract powder, sucrose, and soluble starch, the mixing, granulation, and drying processes can be completed in one go, greatly simplifying the production operation and improving production efficiency. Furthermore, the entire process from raw material input to granulation is carried out in a closed system, which better meets GMP requirements.

[0034] In addition, the present invention has optimized the one-step granulation method. By controlling the air inlet temperature of the granulation equipment, the material is preheated to a suitable temperature and then sprayed with a wetting agent under a suitable pressure for atomization granulation. This ensures easy granulation, uniform granules, suitable density, narrow particle size distribution, good repeatability between different batches of Xiaochaihu granules, and high granule yield. On this basis, further control of the type of wetting agent can avoid a large amount of fine powder or a large amount of 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 effective ingredient content and poor repeatability, the need for high-concentration ethanol to assist granulation, and low yield by continuously controlling multiple key related parameters.

[0036] The present invention further improves the formulation and preparation method, making the prepared Xiaochaihu granules uniform in size.It is uniform and has good formability. While improving children's medication adherence, it can effectively reduce the risk of inactive excipient intake and excessive sucrose intake in children during clinical medication use, thus increasing safety. The Xiaochaihu granules have antipyretic, anti-inflammatory, analgesic, and gastrointestinal regulating effects, making them very suitable for treating diseases including childhood gastroenteritis. Detailed Embodiments

[0037] Experimental methods in the following embodiments of the present invention, unless otherwise specified, 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 listed steps or modules, but may optionally include steps not listed, or may optionally include other steps inherent to these processes, methods, products, or devices.

[0040] The term "and / or" mentioned in this invention describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: 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 powder of a traditional Chinese medicine composition, 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 powder of the traditional Chinese medicine composition as described on page 3 / 18 of the specification (CN 122297626 A) 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);

[0042] The dry extract powder of the traditional Chinese medicine composition is prepared by extracting the active ingredients and then drying the resulting extract. 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 parts- 70 parts, Codonopsis pilosula 40-70 parts, ginger 40-70 parts, licorice 40-70 parts, jujube 40-70 parts.

[0043] Considering that children should not consume too many excipients and have a need for good taste, the inventors of this invention have optimized the formula based on their many years of clinical experience and extensive research. This is achieved by extracting the active ingredients from the Chinese herbal raw materials...The obtained extract is dried to prepare a dry extract powder, and then compounded with appropriate 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 of the Xiaochaihu granules. In the formula, the addition of an appropriate amount of flavoring can not only act as a flavoring agent to enhance the taste of the medicine, but also, together with sucrose and soluble starch, act as excipients compounded with the active ingredient dry extract powder. The three together can further ensure the quality of subsequent granulation of the dry extract powder, and the Xiaochaihu granules obtained are uniform, compact, and have good solubility.

[0044] In some embodiments, the total weight of sucrose and soluble starch to the weight ratio of 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 discovered that the total weight ratio of the excipients (sucrose and soluble starch) to the weight of the dry extract powder of the traditional Chinese medicine composition, as well as the weight ratio of the excipients to sucrose and soluble starch, significantly affect the uniformity of the granules and the yield. When the proportion of the 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 preparation method of 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 Glycyrrhiza uralensis to extraction solvent A, extract 1 to 3 times, combine the extracts, concentrate, filter, and obtain filtrate A;

[0048] (2) Add the 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 clear extract;

[0050] (4) Dry the clear extract to obtain the dry extract 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: Bupleurum, Scutellaria, Codonopsis, Jujube, and Licorice are decocted and extracted with water 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; the decoctions are combined, filtered, and the filtrate is concentrated under reduced pressure to a concentration with a relative density of 1.00-1.20, then filtered again to obtain 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, the weight ratio of the soaked medicinal materials to the weight of 50%-90% ethanol is 1:(4-8); after soaking, adding 50%-90% ethanol for percolation, the weight ratio of the percolated medicinal materials to the added 50%-90% ethanol is 1:(2-6), combining the percolates, recovering ethanol under reduced pressure to a relative density of 1.00-1.20, filtering, and obtaining filtrate B.

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

[0056] In some embodiments, the concentration is made under reduced pressure; preferably, the vacuum degree of the reduced pressure concentration is -0.02Mpa to -0.09Mpa, and the temperature is <95℃. Instructions 4 / 18 pages 7 CN 122297626 A

[0057] In some embodiments, the extract is spray-dried in step (4). Preferably, the inlet air temperature of the spray drying 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 drying weight loss in step (4) is ≤10%.

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

[0060] In some preferred embodiments, the preheating temperature is 40℃-60℃, preferably 45℃-55℃.

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

[0062] The inventors have found that the inlet air temperature of the granulation equipment has no significant effect on the particle content, but it has a significant effect on particle uniformity and yield. When the inlet air temperature is low (60℃), the material is sticky during granulation, there are more coarse particles, and the yield decreases; when the inlet air temperature is high (100℃), the wetting agent dries faster during granulation, and the material is not fully wetted, resulting in more fine powder particles; at the same time, 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 can make the particles uniform, the yield higher, and the drying time shorter, 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 to be within a suitable range. Granulation at different material temperatures will result in different granulation temperatures.There was no significant difference in moisture content and particle size. However, when the material temperature was low (40-45℃), the material exhibited stickiness during granulation, resulting in more coarse particles. When the material temperature was high (55-60℃), the wetting agent dried quickly during granulation, failing to fully wet the material, resulting in more fine powder particles. A material temperature of 45-55℃ was preferred as the preheating endpoint temperature and the starting temperature for granulation spraying. After the granulated material was preheated to a suitable temperature, an appropriate granulation atomization pressure was crucial for ensuring particle uniformity and yield. At a low atomization pressure (1.0 bar), the granulation droplets were large, causing the material to stick and clump, leading to "bed collapse." At a high atomization pressure (5.0 bar), the granulation droplets were small, resulting in rapid drying, insufficient wetting of the material, finer particles, and a decreased yield. An atomization pressure of 2.0 bar to 4.0 bar, and more preferably 2.0 bar to 3.0 bar, was preferred to achieve good atomization 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 a large amount of fine powder or a large amount of 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 a one-step granulation device, control the boiling fluidization of the materials, and preheat the materials;

[0066] ② Granulation: After the materials are preheated, control the boiling fluidization of the materials, uniformly spray the wetting agent for atomized granulation, and after granulation, dry to obtain dry granules;

[0067] ③ Sieving: The dry granules are passed through a vibrating sieve;

[0068] ④ Mixing: Add fragrance to the dry granules obtained by sieving, mix, and obtain the Xiaochaihu granules.

[0069] The present invention also optimizes the preparation method of Xiaochaihu granules. The preparation method of the present invention can realize one-step granulation of Xiaochaihu granules, continuous and automated production. In this invention, the raw materials for preparing Xiaochaihu granules are dry extract powder instead of traditional extract for granulation. The extract obtained after extracting the active ingredients from the traditional Chinese medicine raw materials is spray-dried to obtain dry extract powder. Spray drying allows for automated feeding and continuous production. Furthermore, the optimized formula for preparing Xiaochaihu granules simplifies the raw material preparation process; mixing, granulation, and drying can be completed in one step by simply adding the dry extract powder, sucrose, and soluble starch.This invention greatly simplifies production operations and improves production efficiency. Furthermore, the entire process, from raw material input to granulation output, is conducted in a closed system, better meeting GMP requirements.

[0070] This invention, through continuous control of multiple key related parameters, produces Xiaochaihu granules with high yield, uniform particle size, suitable density, and narrow particle size distribution, effectively solving existing problems such as difficulty in granulation and drying, uneven particle size, large differences in effective ingredient content and poor repeatability, the need for high-concentration ethanol to assist in granulation, and low yield.

[0071] This invention further improves both the formulation and preparation method, resulting in Xiaochaihu granules with uniform particle size and good formability. It also improves children's medication adherence 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 have antipyretic, anti-inflammatory, analgesic, and gastrointestinal function regulating effects, making them very suitable for treating diseases including childhood gastroenteritis.

[0072] The following describes specific embodiments.

[0073] Example 1

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

[0075] Part 1: Preparation of dry powder

[0076] ① Prescription composition: Bupleurum 150kg, Pinellia ternata 56kg, Scutellaria baicalensis 56kg, Codonopsis pilosula 56kg, Glycyrrhiza uralensis 56kg, fresh ginger 56kg, jujube 56kg.

[0077] ② Processing of medicinal materials: Bupleurum chinense, Codonopsis pilosula, Glycyrrhiza uralensis and Scutellaria baicalensis are selected, washed and cut into sections; fresh ginger and Pinellia ternata are selected, washed and coarsely crushed.

[0078] ③ Water extraction: Bupleurum, Scutellaria baicalensis, Codonopsis pilosula, jujube and licorice are decocted with water three times. The weight ratio of the medicinal materials to water in the first decoction is 1:10, and the weight ratio of the medicinal materials to water in the second and third decoctions is 1:8. Each decoction is 2 hours. The decoctions are combined and filtered. The filtrate is concentrated under reduced pressure at a vacuum degree of -0.04Mpa to -0.08Mpa and a temperature of 60 to 90℃ 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 them 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 them 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 extract C;

[0081] ⑥ Spray drying: Clear extract C is spray dried with an inlet air temperature of 140°C, an outlet air temperature of 80°C, and a liquid inlet rate of200mL / min, about 100kg of Xiaochaihu granules dry extract powder was obtained (with a drying loss of about 5%).

[0082] Part Two: Granule Preparation

[0083] The granulation process can be carried out in an "automatic operation" mode. The automatic operation parameters are set as shown in Table 1 below:

[0084] Table 1 Instruction Manual 6 / 18 Page 9 CN 122297626 A

[0085]

[0086] ① Formula composition: 100kg of Xiaochaihu granules dry extract powder, 150kg of sucrose, 150kg of soluble starch, 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 extract powder are ground together through a 60-mesh sieve to obtain the processed raw and auxiliary materials.

[0088] ③ Preheating: Take the processed raw and auxiliary materials and put them 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 volume is 1500M3 / h and the air temperature is 85℃. The material is preheated to 50℃ for 10 minutes.

[0089] ④ Granulation: According to the set "automatic operation" mode parameters, when the material is preheated to 50℃, the air volume is 1500M3 / h, the air temperature is 85℃, the atomization pressure is 3.0 bar, and the wetting agent flow rate is 4kg / min. Purified water is sprayed evenly for granulation. The granulation time is 10 minutes. After granulation, the dry particles are boiled and dried until the moisture content of the dry particles is ≤2.0%. The drying time is 40 minutes to obtain dry particles.

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

[0091] ⑥ Total Mixing: After sieving, the dry granules are added to the orange flavoring and put into a mixer. The speed of the mixer is set to 10 rpm, and the mixture is mixed for 5 minutes.

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

[0093] Example 2

[0094] Part 1: Preparation of Dry Extract Powder

[0095] Same as Example 1.

[0096] Part 2: Granule Preparation

[0097] ① Formula Composition: 100kg of Xiaochaihu Granule Dry Extract Powder, 220kg of sucrose, 180kg of soluble starch, and 1.5kg of orange flavoring (in this example, 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: The sucrose is ground and sieved to 60 mesh, and the soluble starch and dry extract powder are ground together to 60 mesh to obtain the processed raw and auxiliary materials.

[0099] ③ Preheating: The processed raw and auxiliary materials are put 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 1500 m3 / h and the air inlet temperature is 85℃. The material is preheated to 50℃ for 10 minutes.

[0100] ④ Granulation: According to the set "automatic operation" mode parameters, when the material is preheated to 50℃, the air inlet volume is 1500M3 / h, the air inlet temperature is 85℃, the atomization pressure is 3.0 bar, and the wetting agent flow rate is 4kg / min. Purified water is sprayed evenly for granulation. The granulation time is 10min. After granulation, the dry particles are boiled and dried until the moisture content of the dry particles is ≤2.0%. The drying time is 40min to obtain dry particles.

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

[0102] ⑥ Mixing: Orange flavoring is added to the sieved dry particles and put into a mixer. The speed of the mixer is set to 10 rpm and the mixing time is 5 minutes.

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

[0104] Example 3

[0105] Part 1: Dry Extract Powder Preparation Instructions 7 / 18 pages 10 CN 122297626 A

[0106] Same as Example 1.

[0107] Part 2: Granule Preparation

[0108] ① Formula Composition: 100kg of Xiaochaihu granule dry extract powder, 150kg of sucrose, 150kg of soluble starch, 1.2kg of orange flavoring (in this example, 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 and sieved through a 60-mesh sieve, and soluble starch and dry extract powder are ground together through a 60-mesh sieve to obtain the processed raw and auxiliary materials.

[0110] ③ Preheating: Take the processed raw and auxiliary materials and put them into the one-step granulation equipment. The air distribution plate is a cyclone sintering plate. According to the set "automatic operation" mode parameters, the air volume is 1200M3 / h and the air temperature is 90℃. The material is preheated to 50℃ for 10min.

[0111] ④ Granulation: According to the set "automatic operation" mode parameters, when the material is preheated to 50℃, the air volume is 1200M3 / h, the air temperature is 90℃, the atomization pressure is 2.0bar, and the wetting agent flow rate is 3kg / min. Purified water is sprayed evenly for granulation. The granulation time is 13min. After granulation, the dry particles are boiled and dried until the moisture content of the dry particles is ≤2.0%. The drying time is 50min to obtain dry particles.

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

[0113] ⑥ Total Mixing: After sieving, the dry granules are added to an orange flavoring mixer. The mixer speed is set to 10 rpm, and the mixture is mixed for 5 minutes.

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

[0115] Comparative Example 1

[0116] Part 1: Preparation of Dry Extract Powder

[0117] Same as Example 1.

[0118] Part 2: Granule Preparation

[0119] ① Formula Composition: 200 kg of Xiaochaihu granule dry extract powder, 130 kg of sucrose, 70 kg of soluble starch, orange flavoring1.2kg (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 extract powder are ground together through a 60-mesh sieve to obtain processed raw and auxiliary materials.

[0121] ③ Preheating: The processed raw and auxiliary materials are put into a one-step granulation device. The airflow distribution plate is a cyclone sintering plate. According to the set "automatic operation" mode parameters, the air inlet volume is 1500M3 / h and the air inlet temperature is 85℃. The material is preheated to 50℃ for 10 minutes.

[0122] ④ Granulation: According to the set "automatic operation" mode parameters, when the material is preheated to 50℃, the air inlet volume is 1500 m3 / h, the air inlet temperature is 85℃, the atomization pressure is 3.0 bar, and the wetting agent flow rate is 4 kg / min. Purified water is sprayed evenly for granulation. The granulation time is 10 min. After granulation, the dry particles are boiled and dried until the moisture content of the dry particles is ≤2.0%. The drying time is 40 min to obtain dry particles.

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

[0124] ⑥ Mixing: Orange flavoring is added to the sieved dry particles and put into a mixer. The speed of the mixer is set to 10 rpm and the mixture is mixed for 5 minutes.

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

[0126] Example 4

[0127] Part 1: Preparation of Dry Extract Powder

[0128] Same as Example 1.

[0129] Part 2: Granule Preparation

[0130] ① Formula Composition: 100kg of Xiaochaihu Granule Dry Extract Powder, 150kg of sucrose, 150kg of soluble starch, 1.2kg of orange flavoring (in this example, 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 and sieved through a 60-mesh sieve, and soluble starch and dry extract powder are ground together through a 60-mesh sieve to obtain the processed raw and auxiliary materials. Instruction manual, page 8 / 18, CN 122297626 A

[0132] ③ Preheating: Take the processed raw and auxiliary materials and put them into the one-step granulation equipment. The airflow distribution plate is a cyclone sintering plate. Set the airflow rate to 1500 m3 / h and the airflow temperature to 65℃. Preheat the material to 50℃ for 20 min.

[0133] ④ Granulation: When the material is preheated to 50℃, set the airflow rate to 1500 m3 / h and the airflow temperature to 65℃. Set the atomization pressure to 3.0 bar and the wetting agent flow rate to 4 kg / min. Spray purified water evenly for granulation. Granulation time is 10 min. After granulation, boil dry until the moisture content of the dry particles is ≤2.0%. Drying time is 60 min to obtain dry particles.

[0134] ⑤ The dry particles 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, the dry granules are added to the orange flavoring and put into the mixer. The speed of the general mixer is set to 10 rpm and the mixture is mixed for 5 minutes.

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

[0137] Example 5

[0138] Part 1: Preparation of dry extract powder

[0139] Same as Example 1.

[0140] Part 2: Granule preparation

[0141] ① Formula composition: 100kg of Xiaochaihu granule dry extract powder, 150kg of sucrose, 150kg of soluble starch, 1.2kg of orange flavoring (in this example, 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: The sucrose is ground and sieved to 60 mesh, and the soluble starch and dry extract powder are ground together to 60 mesh to obtain the processed raw and auxiliary materials.

[0143] ③ Preheating: Take the processed raw and auxiliary materials and put them 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 volume is 1500M3 / h and the air temperature is 85℃. The material is preheated to 50℃ for 10min.

[0144] ④ Granulation: According to the set "automatic operation" mode parameters, when the material is preheated to 50℃, the air volume is 1500M3 / h, the air temperature is 85℃, the atomization pressure is 1.0bar, and the wetting agent flow rate is 1kg / min. Purified water is sprayed evenly for granulation. The granulation time is 40min. After granulation, the dry particles are boiled and dried until the moisture content of the dry particles is ≤2.0%. The drying time is 40min to obtain dry particles.

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

[0146] ⑥ Total Mixing: After sieving, the dry granules are added to the orange flavoring and put into a mixer. The speed of the mixer is set to 10 rpm, and the mixture is mixed for 5 minutes.

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

[0148] The quality of the granules prepared in the above examples and comparative examples is tested, including taste, granule characteristics, granule yield, and component content.

[0149] Taste: Taste and smell.

[0150] Granule characteristics: Visual inspection.

[0151] Granule yield: Granule yield = Total weight of dry granules after granulation (kg) ÷ [Weight of Xiaochaihu granules dry extract powder (kg) × (1 - Moisture content of dry extract powder (%)) + 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 test: Octadecylsilane-bonded silica gel was used as the packing material (column length 250 mm, inner...The diameter is 4.6 mm and the particle size is 5 μm; acetonitrile is used as mobile phase A and 0.2% phosphoric acid solution is used as mobile phase B, and gradient elution is performed according to the specifications in Table 2; the detection wavelength is 315 nm (for baicalin detection) and 252 nm (for glycyrrhizic acid detection); the column temperature is 25 ℃; the flow rate is 0.8 ml per minute. The theoretical plate number calculated based on the baicalin peak should not be less than 10000.

[0155] Table 2 Specification 9 / 18 pages 12 CN 122297626 A

[0156]

[0157] Preparation of reference solution Take appropriate amounts of baicalin and ammonium glycyrrhizate reference standards, accurately weigh them, add 70% ethanol to prepare a mixed solution containing 250 μg of baicalin and 40 μg of ammonium glycyrrhizate per 1 ml, which is obtained (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, replenish the lost weight with 70% ethanol, shake well, filter, and take the filtrate to obtain the test solution.

[0159] Assay: Accurately pipette 10μl each of the reference solution and the test solution, inject into the liquid chromatograph, and determine to obtain the test solution.

[0160] The results are entered in Table 3:

[0161] Table 3

[0162]

[0163]

[0164] As can be seen from 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 with Example 1, in the preparation process of Xiaochaihu granules in Example 4, the granulation equipment was set with a lower inlet air temperature (65 ℃), which led to an increase in coarse particles during the granulation process, a decrease in particle yield, a slight decrease in the content of baicalin and glycyrrhizic acid, and a worse repeatability 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 the present invention. Setting the inlet air temperature of the granulation equipment to 70℃-100℃ is more conducive to the preparation of Xiaochaihu granules of the present invention and improves the quality of Xiaochaihu granules.

[0166] Compared with Example 1, in the preparation process of Xiaochaihu granules in Example 5, the atomization pressure was too low (1.0 bar), resulting in fine granules, more fine powder, decreased granule yield, slightly decreased content of baicalin and glycyrrhizic acid, and poorer repeatability of the preparation process. This indicates that the atomization pressure during the granulation process will significantly affect the granule properties and yield of the prepared Xiaochaihu granules, and the preferred atomization pressure is 2.0 bar-4.0 bar.

[0167] Compared with Example 1, in the preparation of Xiaochaihu granules in Comparative Example 1, the weight ratio of sucrose to soluble starch was too high (1.86:1), and the weight ratio of excipients to dry extract powder was too low (1:1), resulting in a reduced granule taste, material stickiness and clumping during granulation, difficulty in granulation, and a significant decrease in granule yield. The repeatability of the preparation process was also significantly worse. This shows that the ratio of raw materials used in the preparation of Xiaochaihu granules in this invention has a very important influence on the taste, granule quality, and ease of granulation of the prepared Xiaochaihu granules. In this invention, the preferred 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 can ensure easy granulation, uniform granules, high granule yield, and good granulation repeatability.

[0168] Example 6

[0169] Part 1: Screening of prescription composition

[0170] In the following studies, granules were prepared according to the preparation method described in Example 1.

[0171] ① Survey of commonly used diluents for granules

[0172] The survey of commonly used diluents for granules includes sucrose, dextrin, mannitol, soluble starch, lactose, etc. The advantages and disadvantages of each diluent were compared, and diluents were initially screened for prescription screening and investigation. See Table 4 below for details:

[0173] Table 4

[0174]

[0175]

[0176] Based on their own experience, combined with the situation of 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 in children, and microcrystalline cellulose is often used in suspension granules. Sucrose, dextrin, soluble starch, and corn starch were further selected for prescription 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, different excipients were mixed with dry extract powder and ground to 60 mesh for one-step granulation. Granule yield, granule properties, solubility, and taste were used as evaluation indicators. See Table 5 below for details: Instruction Manual 11 / 18 pages 14 CN 122297626 A

[0179] Table 5

[0180]

[0181] Under the premise that the weight ratio of excipients to dry extract powder is 5:1, sucrose granulation has good formability and uniform granules, and also acts as a flavoring agent; soluble starch, corn starch and dextrin granules are fine, but there is room for further reduction of excipient dosage, and the taste is poor; in view of the above, in order to reduce the amount of excipients while ensuring granule formability and taste, it is preferable to use sucrose in combination with other excipients for formulation investigation.

[0182] ③ Comparison of Granulation Effects with Different Excipient Combinations

[0183] To investigate the effect of sucrose combined with different excipients and dry extract powder on granulation, sucrose was combined 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 subjected to granulation.Granulation was performed step by step, with granule yield, granule characteristics, solubility, and taste 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 which sucrose combined with dextrin produces more fine powder; the solubility and taste were examined, among which sucrose combined with corn starch had poor solubility, and sucrose combined with dextrin had a slightly astringent taste. The preferred combination was sucrose combined with soluble starch for formulation evaluation.

[0187] ④ Comparison of Granulation Effects with Different Auxiliary Material Ratios

[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 auxiliary materials. The sucrose was ground to 60 mesh, and the soluble starch and dry extract powder were ground to 60 mesh and then granulated in one step. Granulation yield, granule characteristics, solubility, and taste were used as evaluation indicators. See Table 7 below for details:

[0189] Table 7 Instruction Manual 12 / 18 pages 15 CN 122297626 A

[0190]

[0191] Under the premise that the weight ratio of auxiliary materials to dry extract powder is 5:1, the ratios of sucrose to soluble starch are 2:1, 1.5:1, 1:1, 1:1.5, Both a 1:2 ratio can be used for granulation. However, when the sucrose content is higher (2:1), the material becomes sticky during granulation, resulting in more coarse particles and a lower yield. When the soluble starch content is higher (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 of Different Ratios of Excipients and Dry Extracts

[0193] To investigate the effect of different ratios of excipients and dry extracts on granulation, one-step granulation was carried out using different ratios of excipients and extracts. Granulation yield, granule characteristics, solubility, and taste 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 ratios of excipient to dry extract of 5:1, 4:1, 3:1, 2:1, and 1:1 can all be used for granulation. When the proportion of dry extract is high (1:1), the material is sticky during granulation, there are more coarse particles, and the yield decreases. The preferred weight ratio of excipient to dry extract is 5:1-2:1, with a weight ratio of 3:1 being the best. The granulation yield is high, the amount of excipient is small, and the solubility and taste meet the requirements.

[0197] Part Two: Selection of Airflow Distribution Plate

[0198] To investigate the effect of airflow distribution plate on granulation, different airflow distribution plates were tested separately, with particle yield and particle properties as evaluation indicators, as detailed in Table 9 below:

[0199] Table 9 Specification 13 / 18 pages 16 CN 122297626 A

[0200]

[0201] Under the premise that the amount of excipients and dry powder is the same, the use of cyclone sintering plate can more effectively fluidize materials and improve granulation efficiency.The result is better, and the loss of fine powder through the airflow distribution plate is reduced, which can further improve the particle yield. The airflow distribution plate is preferably a cyclone sintering plate.

[0202] Part 3: Investigation of key process parameters

[0203] The following study uses the formulation described in Example 1 for granulation.

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

[0205] In order to investigate the effect of different inlet air temperatures on granulation, the same formulation material was used, and one-step granulation was carried out at different inlet air temperatures. The particle yield, particle properties, drying time and content were used as evaluation indicators, as detailed in Table 10 below:

[0206] Table 10

[0207]

[0208] There was no significant difference in particle content when granulating at each inlet air temperature. The inlet air temperature had little effect on the content. However, when the inlet air temperature is low (60℃), the material becomes sticky during granulation, resulting in more coarse particles and a lower yield. When the inlet air temperature is high (100℃), the wetting agent dries too quickly during granulation, failing to fully wet the material and resulting in more fine powder particles. Furthermore, the higher the inlet air temperature, the shorter the drying time. An inlet air temperature of 70-100℃ is preferred, with 80-90℃ being optimal, resulting in uniform particles, high yield, and short drying time, thus 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 granulation was performed in one step at different material temperatures. The granule yield, granule properties, moisture content, and content were used as evaluation indicators, as detailed in Table 11 below:

[0211] Table 11 Instruction Manual 14 / 18 pages 17 CN 122297626 A

[0212]

[0213] There was no significant difference in granule moisture content and content at different material temperatures. However, when the material temperature was low (40-45 ℃), the material exhibited stickiness during granulation, resulting in more coarse particles; when the material temperature was high (55-60 ℃), the wetting agent dried faster during granulation, failing to fully wet the material, resulting in more fine powder particles; the preferred material temperature was 45-55 ℃, and 50 ℃ was selected as the preheating endpoint temperature and the granulation spray start temperature.

[0214] ③ Comparison of Granulation Effects under Different Atomization Pressures

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

[0216] Table 12

[0217]

[0218] There was no significant difference in particle moisture content and content under different atomization pressures. However, at lower atomization pressures (1.0 bar), the granulation droplets were larger, the material became sticky and agglomerated, and "bed collapse" occurred; at higher atomization pressures (5.0 bar), the granulation droplets were smaller, the drying speed was faster, the material was not fully wetted, the particles were finer, and the yield decreased; the preferred atomization pressure was 2.0 bar to 4.0 bar, which had a good atomization effect, 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 material was used, and one-step granulation was carried out using different wetting agents. The particle yield, particle properties, drying time, and content were used as evaluation indicators, as detailed in Table 13 below:

[0221] Table 13 Instruction Manual 15 / 18 pages 18 CN 122297626 A

[0222]

[0223] There was no significant difference in particle content when using different wetting agents for granulation. However, when the ethanol concentration was high (50% ethanol), the wetting agent dried faster and did not fully wet the material, resulting in finer particles and a decrease in yield. It is preferable to use purified water as a wetting agent, which can improve the yield and reduce the use of organic solvents, thereby improving the convenience of production operations.

[0224] ⑤ Comparison of different total mixing times

[0225] In order to investigate the effect of different total mixing times on product quality, the same formula materials were granulated and then the mixing uniformity was investigated. See Table 14 below for details:

[0226] Table 14

[0227]

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

[0229] ⑥ Comparison of preferred processes

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

[0231] Table 15 Specification 16 / 18 pages 19 CN 122297626 A

[0232]

[0233]

[0234] As can be seen from 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 2.0bar-3.0bar, material temperature control 45℃-55℃ (preheating endpoint temperature 50℃), and the wetting agent is purified water, which can ensure easy granulation and make the obtained Xiaochaihu granules uniform and have 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 Xiaochaihu granules of the present invention first optimize the formula by drying the extract obtained after extracting the active ingredients from the raw materials of traditional Chinese medicine into a dry powder, and then compounding it with appropriate excipients sucrose and soluble starch. Furthermore, the total amount of the dry powder and excipients, as well as the ratio of the amount of excipients sucrose and soluble starch, are controlled to obtain the preparation formula of the Xiaochaihu granules. In the formula, the addition of an appropriate amount of flavoring can not only act as a flavoring agent to increase the taste of the medicine, but also, together with sucrose and soluble starch, act as excipients compounded with the active ingredient dry powder. Together, the three can further ensure the quality of the subsequent granulation of the dry powder. The Xiaochaihu granules obtained are uniform, compact, and have good solubility. Specification 17 / 18 pages 20 CN 122297626 A

[0239] The present invention further optimizes the preparation method of Xiaochaihu granules. The preparation method of the present invention can realize one-step granulation, continuous and automated production of Xiaochaihu granules. The preparation method of the present invention, through continuous control of multiple key related parameters, makes the prepared Xiaochaihu granules have a high yield, uniform granules, suitable looseness, narrow particle size distribution, and good repeatability between different batches of products.

[0240] The present invention further improves the formulation and preparation method, making the prepared Xiaochaihu granules uniform and well-formed. Moreover, it can improve the medication compliance of children, effectively reduce the risk of inactive excipient intake and excessive sucrose intake in children during clinical medication, and increase safety. The Xiaochaihu granules have antipyretic, anti-inflammatory, analgesic and gastrointestinal regulating effects, and are very suitable for treating diseases including gastroenteritis in children.

[0241] The technical features of the above embodiments can be combined arbitrarily. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as the combination of these technical features does not contradict each other, it should be considered as within the scope of this specification.

[0242] The above embodiments only illustrate several implementation methods of the present invention, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the present invention. It should be noted that for those skilled in the art, several modifications and improvements can be made without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of the present invention should be determined by the appended claims. Specification 18 / 18 Page 21 CN 122297626 A Abstract The present invention provides a pediatric Xiao Chai Hu (Bupleurum) Granule and the preparation method thereof. The Xiao Chai Hu Granule is prepared from the raw materials of dry extract powder of a traditional Chinese medicine (TCM) composition, sucrose, soluble starch, and essence. The weight ratio of the total weight of sucrose and soluble starch to the dry extract powder of the TCMcomposition is (2-5):1; the weight ratio of sucrose to soluble starch ranges from 1:1.5 to 1.5:1; and the weight ratio of essence to the dry extract powder of the TCM composition is (0-5):(100-500). The dry extract powder of the TCM composition is prepared by drying a clear extract obtained after extracting active ingredients from raw materials. By optimizing the formula, the Xiao Chai Hu Granule of the present invention can maintain a good taste while significantly reducing the total amount of excipients and the dosage of sucrose. Meanwhile, it ensures that the prepared Xiao Chai Hu Granule has uniform particles with appropriate tightness, improves the compliance and safety of pediatric medication, and reduces the risks of inactive excipient intake during clinical medication for pediatric patients and excessive sucrose intake for children in the developmental stage.

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.