Lucxian granules as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a poria cocos and herba epimedii granule as well as a preparation method and application thereof. The raw materials of the Lingxian granules comprise traditional Chinese medicine components and auxiliary materials, the traditional Chinese medicine components comprise rhizoma smilacis glabrae, radix clematidis, plantain herb, polygonum cuspidatum, rhizoma dioscoreae hypoglaucae, cortex phellodendri and rhizoma atractylodis; the auxiliary materials comprise starch sodium octenylsuccinate, sulfobutyl ether-beta-cyclodextrin, soybean phospholipid, ethyl cellulose and isomaltitol. Specific auxiliary materials and a preparation process are selected, so that the finally prepared Lingxian granules have good forming rate, moisture absorption rate and dissolution rate.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a Lingxian granule, its preparation method, and its application. Background Technology

[0002] Hyperuricemia and gout are common metabolic diseases, and traditional Chinese medicine (TCM) has unique advantages and potential in treating them. Lingxian Granules are known to consist of seven herbs: Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense, and Atractylodes lancea. Smilax glabra is the principal herb, clearing turbidity and resolving stagnation, eliminating dampness and detoxifying, and promoting joint mobility. Clematis chinensis dispels wind and dampness, promotes menstruation, and Plantago asiatica clears heat, resolves phlegm, promotes urination, and detoxifies; these are the assistant herbs. Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense, and Atractylodes lancea serve as adjuvant herbs, enhancing the formula's effects of clearing dampness and detoxifying, resolving phlegm and removing blood stasis, and strengthening the spleen and regulating qi. The entire formula works synergistically to clear dampness and turbidity, promote qi circulation and remove blood stasis, strengthen the spleen and relieve numbness, making it particularly effective in treating hyperuricemia caused by phlegm-dampness obstruction and internal damp-heat.

[0003] However, existing Lingxian granules have some shortcomings in production and clinical use: for example, poor granule uniformity leads to differences in drug content between single doses, affecting the stability of efficacy; unsatisfactory solubility or dispersibility affects the absorption rate and bioavailability of the drug; or during the preparation process, some active ingredients may be lost or destroyed due to process problems, affecting the final efficacy. In addition, different excipient selections and their ratios directly affect the granule's formability, flowability, hygroscopicity, stability, and taste, thus affecting the overall quality of the product and patient compliance.

[0004] For example, patent CN102078543A discloses a traditional Chinese medicine for treating gout and its preparation method. The components and weight proportions of the raw materials in this traditional Chinese medicine preparation are: 8 parts Smilax glabra, 6 parts Alisma plantago-aquatica, 6 parts Salvia miltiorrhiza, 6 parts Dioscorea hypoglauca, 2 parts Cornus officinalis, 2 parts Rheum palmatum, 6 parts Celastrus orbiculatus, and 2 parts Citrus aurantium. The dosage forms of this traditional Chinese medicine preparation include oral liquid, tablets, capsules, and granules. This traditional Chinese medicine preparation has the functions of clearing heat and dampness, promoting blood circulation and unblocking collaterals, reducing swelling and relieving pain, and can significantly alleviate the clinical symptoms of gout patients and reduce recurrence, as well as lower blood uric acid, blood lipid levels, and serum creatinine. However, the granules obtained by this invention have poor taste and poor solubility.

[0005] For example, the literature "Pharmacodynamic Study of Lingxian Jiangsuan Granules in the Treatment of Hyperuricemia," a master's thesis from Shanghai University of Traditional Chinese Medicine, explored the pharmacodynamic effects and mechanism of action of Lingxian Jiangsuan Granules in treating hyperuricemia, providing preliminary theoretical basis for new drug development. Although this study confirmed that medium and high doses of Lingxian Jiangsuan Granules could effectively reduce serum UA levels in hyperuricemic mice, the medium and high doses of Lingxian Jiangsuan Granules significantly reduced serum UA, BUN, Cr, TG, TC, and liver ADA levels in rats with hyperuricemia and renal failure, improving renal function in rats while lowering uric acid. Its mechanism of lowering uric acid and improving renal function was not related to XOD enzyme activity, but may be related to increased uric acid excretion. However, this invention did not investigate the effect of preparing Lingxian granules into a granule form.

[0006] Therefore, there is an urgent need to develop a Lingxian granule formulation with good particle uniformity, rapid dissolution, stable efficacy, and suitable taste. Summary of the Invention

[0007] The purpose of this invention is to provide: a Lingxian granule, its preparation method and application, and related technologies, to solve technical problems such as poor particle uniformity, poor solubility, poor taste, or combinations thereof.

[0008] Terminology Explanation:

[0009] Unless otherwise defined, all technical terms in this document have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter of the claims pertains. Unless otherwise stated, all patents, patent inventions, and publications cited in this document are incorporated herein by reference in their entirety. If multiple definitions exist for terms in this document, the definitions in this chapter shall prevail.

[0010] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0011] The definition of standard chemical terms can be found in the reference "Pharmacopoeia of the People's Republic of China (2025 Edition), China Medical Science and Technology Press, March 2025".

[0012] Unless specifically defined herein, the use of all commercially available products herein employs standard techniques. For example, it may be carried out using the manufacturer's instructions for use with the kit, or in accordance with methods known in the art or the description of this invention. The techniques and methods described herein can generally be implemented according to conventional methods well known in the art, based on the descriptions in the various summary and more specific documents cited and discussed in this specification.

[0013] In a first aspect, the present invention provides Lingxian granules, wherein the raw materials of Lingxian granules include traditional Chinese medicine ingredients and excipients; the traditional Chinese medicine ingredients are composed of Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense and Atractylodes lancea; the excipients include sodium octenyl succinate starch, sulfobutyl ether-β-cyclodextrin, soybean lecithin, ethyl cellulose and isomaltitol.

[0014] Preferably, the mass ratio of sodium octenyl succinate starch, sulfobutyl ether-β-cyclodextrin, soybean lecithin, ethyl cellulose and isomaltitol is 3-5:7-12:5-10:4-6:30-40.

[0015] More preferably, the mass ratio of sodium octenyl succinate starch, sulfobutyl ether-β-cyclodextrin, soybean lecithin, ethyl cellulose and isomaltitol is 5:10:8:5:32.

[0016] Preferably, the mass ratio of the traditional Chinese medicine ingredients to the excipients is 30-50:50-80.

[0017] More preferably, the mass ratio of the traditional Chinese medicine ingredients to the excipients is 30-50:56-71.

[0018] Preferably, the mass ratio of Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense, and Atractylodes lancea is 6-8:2-4:6-8:3-5:3-5:2-4:1-2.

[0019] More preferably, the mass ratio of Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense, and Atractylodes lancea is 7:3:7:4:4:3:2.

[0020] Preferably, the ingredients, by weight, include the following: 30-50 parts of traditional Chinese medicine ingredients, 3-10 parts of sodium octenyl succinate starch, 7-12 parts of sulfobutyl ether-β-cyclodextrin, 5-10 parts of soybean lecithin, 4-6 parts of ethyl cellulose, and 30-40 parts of isomaltitol.

[0021] Preferably, the raw material further includes a solvent, wherein the solvent is water.

[0022] Preferably, the water is selected from deionized water, pure water, or distilled water.

[0023] More preferably, the water is pure water.

[0024] Secondly, the present invention provides a method for preparing the above-mentioned Lingxian granules, comprising the following steps: S1: Powder Atractylodes lancea and Clematis chinensis, add water, extract by steam distillation, and collect the volatile oil and residue; S2: The residue from step S1, Smilax glabra, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca and Phellodendron chinense are mixed and extracted with an ethanol solution containing 0.2-0.8 wt% hydrochloric acid 1-3 times, each time for 1-2 hours. The extracts are combined and concentrated under reduced pressure at 55-65℃ to obtain the Chinese herbal extract. S3: Add ethanol to the Chinese herbal extract to a final concentration of 70-78% (v / v), let it stand at 0-5℃ for 20-26 hours, take the supernatant to recover the ethanol until there is no alcohol taste, add soybean lecithin and mix, homogenize and disperse and then dry to obtain phospholipid complex Chinese herbal extract powder. S4: Sulfobutyl ether-β-cyclodextrin is mixed with water to obtain an inclusion solution; S5: Mix the volatile oil from step S1 with the inclusion solution from step S4, shear emulsify for 3-6 minutes, stir and include for 5-7 hours, and freeze dry to obtain volatile oil microcapsule powder. S6: The phospholipid compound Chinese herbal extract powder, isomaltitol, and sodium octenyl succinate starch from step S3 are added to a fluidized bed and mixed. Then, 25wt%-35wt% ethyl cellulose aqueous dispersion is used as a binder for spray granulation and granulation to obtain granules. S7: The volatile oil microcapsule powder from step S5 is mixed with the raw granules from step S6 and granulated to obtain the final product.

[0025] Preferably, in step S1, the Atractylodes lancea and Clematis chinensis powder needs to be passed through a 40-60 mesh sieve.

[0026] Preferably, in step S1, the total mass of Atractylodes lancea and Clematis chinensis is in a liquid-to-water ratio of 1g:5-10mL.

[0027] Preferably, in step S2, the Smilax glabra, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, and Phellodendron chinense are pulverized and passed through a 40-60 mesh sieve.

[0028] Preferably, in step S2, the total mass of the medicinal residue, Smilax glabra, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, and Phellodendron chinense is in a material-to-liquid ratio of 1g:10-20mL to the ethanol solution.

[0029] Preferably, in step S2, the mass fraction of ethanol in the ethanol solution is 55%-65%.

[0030] Preferably, in step S2, the relative density of the herbal extract is 1.10-1.15 (60℃).

[0031] Preferably, in step S4, the mass-to-volume ratio of the sulfobutyl ether-β-cyclodextrin to water is 1g:3-5mL; Preferably, in step S5, the temperature of the stirring and encapsulation is 35-40°C.

[0032] Preferably, in step S6, the parameters for spray granulation are: inlet air temperature 65-70℃, material temperature 45-50℃, and drying to a moisture content ≤3.0%.

[0033] Preferably, in step S7, the mixing and granulation time is 10-20 minutes.

[0034] Thirdly, the present invention provides the application of the above-mentioned Lingxian granules in the preparation of a drug for treating gout.

[0035] The present invention has the following beneficial effects: (1) This invention solves the problem of high hygroscopicity of Lingxian granules obtained by traditional process: the macromolecular polysaccharides and mucilage in the medicinal materials are removed by a specific preparation method, reducing hygroscopicity from the source. Furthermore, ethyl cellulose aqueous dispersion is used as a binder for granulation. After drying, a continuous hydrophobic polymer network skeleton is formed inside and on the surface of the granules, blocking the water channels. Combined with the hydrophobic micro-region barrier effect of sodium octenyl succinate starch (OSA) and the low hygroscopicity of isomaltitol, the critical relative humidity (CRH) of the finished product is increased from 65% of traditional granules to more than 90%.

[0036] (2) This invention significantly reduces the degradation of active ingredients through multiple stabilization mechanisms: soybean phospholipids and extracts form phospholipid complexes, and the phospholipid bilayer encapsulates resveratrol (Polygonum cuspidatum) and berberine (Phellodendron amurense), isolating them from oxygen and light and preventing oxidative degradation; sulfobutyl ether-β-cyclodextrin is used to encapsulate volatile oils, and freeze-drying process is combined to avoid damage to volatile oils caused by high temperature; the volatile oil microencapsulation method is used to avoid heat loss and shear damage during granulation; and extraction with hydrochloric acid-containing ethanol is used to stabilize alkaloids by salt formation, inhibit enzymatic hydrolysis, and further improve chemical stability.

[0037] (3) The present invention significantly improves the bioavailability of the product through specific excipients and preparation methods. Isomaltitol is used to replace traditional sucrose or dextrin, which has a very low glycemic index and does not participate in insulin metabolism, making it particularly suitable for the target patient group of Lingxian Granules (patients with gout and hyperuricemia often have metabolic syndrome or diabetes risk). Furthermore, the inclusion of phospholipid complex and cyclodextrin effectively masks the bitterness of Phellodendron bark and the pungent taste of Atractylodes lancea, while isomaltitol provides a mild sweetness, significantly improving patient compliance and taste. Detailed Implementation

[0038] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention. Unless otherwise specified, the materials and reagents used are commercially available.

[0039] Example 1 A type of Lingxian granules Based on mass parts, it consists of the following ingredients: 40 parts of traditional Chinese medicine ingredients, 5 parts of sodium octenyl succinate starch, 10 parts of sulfobutyl ether-β-cyclodextrin, 8 parts of soybean lecithin, 5 parts of ethyl cellulose and 32 parts of isomaltitol.

[0040] The herbal ingredients consist of the following components in a mass ratio of 7:3:7:4:4:3:2: Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense, and Atractylodes lancea.

[0041] The preparation method of the Lingxian granules is as follows: S1: After crushing Atractylodes lancea and Clematis chinensis into powder, sieve them through a 60-mesh sieve. Add water at a material-to-liquid ratio of 1g:8mL and extract by steam distillation. Collect the volatile oil and residue. S2: Smilax glabra, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca and Phellodendron chinense are pulverized and passed through a 40-mesh sieve. They are then mixed with the residue from step S1. A 60wt% ethanol solution containing 0.5wt% hydrochloric acid is added at a material-to-liquid ratio of 1g:15mL. The mixture is heated and refluxed twice, each time for 1.5h. The extracts are combined and concentrated under reduced pressure at 60℃ to obtain a traditional Chinese medicine extract. S3: Add ethanol to the Chinese herbal extract to a final concentration of 75%, let it stand at 0℃ for 24 hours, take the supernatant to recover the ethanol until there is no alcohol odor, add soybean lecithin and mix, homogenize and disperse, and then dry to obtain phospholipid complex Chinese herbal extract powder; the relative density is 1.10-1.15 (60℃); S4: Sulfobutyl ether-β-cyclodextrin and water were mixed at a mass-volume ratio of 1 g: 4 mL to obtain an inclusion solution; S5: Mix the volatile oil from step S1 with the inclusion solution from step S4, shear emulsify for 5 min, stir and include at 35°C for 6 h, freeze dry to obtain volatile oil microcapsule powder. S6: The phospholipid compound Chinese herbal extract powder, isomaltitol, and sodium octenyl succinate starch from step S3 are added to a fluidized bed and mixed. Then, 30 wt% ethyl cellulose aqueous dispersion is used as a binder for spray granulation. The inlet air temperature is 70℃, the material temperature is 45℃, and the material is dried until the moisture content is ≤3.0%. The granules are then sized to obtain the granules. S7: The volatile oil microcapsule powder from step S5 is mixed with the raw material particles from step S6 and granulated for 15 minutes to obtain the final product.

[0042] Example 2 A type of Lingxian granules Based on mass parts, it consists of the following ingredients: 30 parts of traditional Chinese medicine ingredients, 10 parts of sodium octenyl succinate starch, 12 parts of sulfobutyl ether-β-cyclodextrin, 5 parts of soybean lecithin, 4 parts of ethyl cellulose, and 40 parts of isomaltitol.

[0043] The herbal ingredients consist of the following components in a mass ratio of 6:4:6:5:3:4:1: Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense, and Atractylodes lancea.

[0044] The preparation method of the Lingxian granules is as follows: S1: After crushing Atractylodes lancea and Clematis chinensis into powder, sieve them through a 60-mesh sieve. Add water at a material-to-liquid ratio of 1g:5mL and extract by steam distillation. Collect the volatile oil and the residue. S2: Smilax glabra, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca and Phellodendron chinense are pulverized and passed through a 40-mesh sieve. They are then mixed with the residue from step S1. A 55wt% ethanol solution containing 0.2wt% hydrochloric acid is added at a material-to-liquid ratio of 1g:20mL. The mixture is heated and refluxed once for 2 hours each time. The extracts are combined and concentrated under reduced pressure at 55℃ to obtain a traditional Chinese medicine extract. S3: Add ethanol to the Chinese herbal extract to a final concentration of 70%, let it stand at 5℃ for 20 hours, take the supernatant to recover the ethanol until there is no alcohol odor, add soybean lecithin and mix, homogenize and disperse, and then dry to obtain phospholipid complex Chinese herbal extract powder; the relative density is 1.10-1.15 (60℃); S4: Sulfobutyl ether-β-cyclodextrin and water were mixed at a mass-volume ratio of 1 g: 5 mL to obtain an inclusion solution; S5: Mix the volatile oil from step S1 with the inclusion solution from step S4, shear emulsify for 3 min, stir and include at 40°C for 5 h, freeze dry to obtain volatile oil microcapsule powder. S6: The phospholipid compound Chinese herbal extract powder, isomaltitol, and sodium octenyl succinate starch from step S3 are added to a fluidized bed and mixed. Then, 25 wt% ethyl cellulose aqueous dispersion is used as a binder for spray granulation. The inlet air temperature is 65℃, the material temperature is 50℃, and the material is dried until the moisture content is ≤3.0%. The granules are then sized to obtain the granules. S7: The volatile oil microcapsule powder from step S5 is mixed with the raw granules from step S6 and granulated for 10 minutes to obtain the final product.

[0045] Example 3 A type of Lingxian granules Based on mass parts, it consists of the following ingredients: 50 parts of traditional Chinese medicine ingredients, 3 parts of sodium octenyl succinate starch, 7 parts of sulfobutyl ether-β-cyclodextrin, 10 parts of soybean lecithin, 6 parts of ethyl cellulose, and 30 parts of isomaltitol.

[0046] The herbal ingredients consist of the following components in a mass ratio of 8:2:8:3:5:2:2: Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense, and Atractylodes lancea.

[0047] The preparation method of the Lingxian granules is as follows: S1: After crushing Atractylodes lancea and Clematis chinensis into powder, sieve them through a 60-mesh sieve. Add water at a material-to-liquid ratio of 1g:10mL and extract by steam distillation. Collect the volatile oil and the residue. S2: Smilax glabra, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca and Phellodendron chinense are pulverized and passed through a 40-mesh sieve. They are then mixed with the residue from step S1. A 65wt% ethanol solution containing 0.8wt% hydrochloric acid is added at a material-to-liquid ratio of 1g:10mL. The mixture is heated and refluxed three times, each time for 1 hour. The extracts are combined and concentrated under reduced pressure at 65℃ to obtain a traditional Chinese medicine extract. S3: Add ethanol to the Chinese herbal extract to a final concentration of 78%, let it stand at 3℃ for 26 hours, take the supernatant to recover the ethanol until there is no alcohol odor, add soybean lecithin and mix, homogenize and disperse, and then dry to obtain phospholipid complex Chinese herbal extract powder; the relative density is 1.10-1.15 (60℃); S4: Sulfobutyl ether-β-cyclodextrin and water were mixed at a mass-volume ratio of 1 g: 3 mL to obtain an inclusion solution; S5: Mix the volatile oil from step S1 with the inclusion solution from step S4, shear emulsify for 6 min, stir and include at 35°C for 7 h, freeze dry to obtain volatile oil microcapsule powder. S6: The phospholipid compound Chinese herbal extract powder, isomaltitol, and sodium octenyl succinate starch from step S3 are added to a fluidized bed and mixed. Then, 35 wt% ethyl cellulose aqueous dispersion is used as a binder for spray granulation. The inlet air temperature is 70℃, the material temperature is 45℃, and the material is dried until the moisture content is ≤3.0%. The granules are then sized to obtain the granules. S7: Mix the volatile oil microcapsule powder from step S5 with the raw granules from step S6 for 20 minutes to granulate, and you will get the product.

[0048] Comparative Example 1 The difference from Example 1 is that an equal amount of ethyl cellulose is replaced with microcrystalline cellulose, and the rest is the same as in Example 1.

[0049] Comparative Example 2 The difference from Example 1 is that an equal amount of sodium octenyl succinate starch is replaced with pregelatinized starch, and the rest is the same as in Example 1.

[0050] Comparative Example 3 The difference from Example 1 is that the specific amount of excipients is changed. Specifically, by mass, it consists of the following components: 40 parts of traditional Chinese medicine ingredients, 2 parts of sodium octenyl succinate starch, 15 parts of sulfobutyl ether-β-cyclodextrin, 4 parts of soybean lecithin, 10 parts of ethyl cellulose and 29 parts of isomaltitol.

[0051] Everything else is the same as in Example 1.

[0052] Comparative Example 4 The difference from Example 1 is that the preparation method is changed, specifically: S1. First, grind Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense, and Atractylodes lancea into 50-mesh powder, soak in water for 1.5 hours, then decoct in water twice for 2 hours each time. The amount of water used for each decoction is 8 times the total weight of Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense, and Atractylodes lancea. Filter, combine the filtrates, concentrate and dry to obtain an extract, which is the Chinese medicine component. The relative density of the extract at 60℃ is 1.10-1.15. S2. Mix the Chinese herbal ingredients with all excipients and granulate (15 mesh) to prepare Lingxian granules.

[0053] Effect Experiment The Lingxian granules prepared in Examples 1-3 and Comparative Examples 1-4 were tested for the following indicators: (1) Determination of molding rate: The double sieve method was used in the particle size section of the 2020 edition of the Pharmacopoeia of the People's Republic of China, Part IV. Particles that can pass through sieve No. 1 but cannot pass through sieve No. 5 are qualified particles.

[0054] Pellet forming rate (%) = weight of qualified pellets / total weight of pellets × 100%.

[0055] (2) Hygroscopicity determination: A glass desiccator was filled with a supersaturated sodium chloride solution at the bottom and placed at room temperature for 48 hours to allow the desiccator to reach equilibrium with a relative humidity of 75%. Approximately 2.0 g of sample was accurately weighed and placed in a pre-dried 5 mL weighing bottle. The bottle was gently shaken to distribute the sample evenly and then placed in the desiccator containing the supersaturated sodium chloride solution (with the weighing bottle cap open). The sample was weighed after 12 hours, and the percentage of moisture absorption was calculated using the following formula. A lower moisture absorption rate indicates less hygroscopicity and greater stability of the particles.

[0056] Moisture absorption percentage (%) = [(Weight of particles after moisture absorption - Weight of particles before moisture absorption) / Weight of particles before moisture absorption] × 100%.

[0057] (3) Determination of solubility: The solubility was determined according to the "Solubility" method under the General Chapter 0104 Granules in Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China, and the solubility was calculated.

[0058] Solubility (%) = [(sample weight - weight of insoluble matter) / sample weight] × 100%.

[0059] (4) Determination of tap density: The tap density was determined according to the tap density determination method in Section IV, General Chapter 0993 of the 2020 edition of the Pharmacopoeia of the People's Republic of China.

[0060] The results are shown in Table 1 below: Table 1

[0061] As can be seen from the above data, the Lingxian granules prepared in the embodiments of the present invention have good molding rate, low tap density, low moisture absorption rate, and high solubility.

[0062] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A Lingxian granule, characterized in that, The raw materials of the Lingxian granules include traditional Chinese medicine ingredients and excipients; the traditional Chinese medicine ingredients are composed of Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense and Atractylodes lancea; the excipients include sodium octenyl succinate starch, sulfobutyl ether-β-cyclodextrin, soybean lecithin, ethyl cellulose and isomaltitol.

2. The Lingxian granules according to claim 1, characterized in that, The mass ratio of the Chinese herbal ingredients to the excipients is 30-50:50-80.

3. The Lingxian granules according to claim 1, characterized in that, The mass ratio of Smilax glabra, Clematis chinensis, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca, Phellodendron chinense, and Atractylodes lancea is 6-8:2-4:6-8:3-5:3-5:2-4:1-2.

4. The Lingxian granules according to claim 1, characterized in that, By weight, it includes the following ingredients: 30-50 parts of traditional Chinese medicine ingredients, 3-10 parts of sodium octenyl succinate starch, 7-12 parts of sulfobutyl ether-β-cyclodextrin, 5-10 parts of soybean lecithin, 4-6 parts of ethyl cellulose, and 30-40 parts of isomaltitol.

5. The Lingxian granules according to claim 1, characterized in that, The raw materials also include a solvent, which is water.

6. The method for preparing Lingxian granules according to any one of claims 1-5, characterized in that, Includes the following steps: S1: Powder Atractylodes lancea and Clematis chinensis, add water, extract by steam distillation, and collect the volatile oil and residue; S2: The residue from step S1, Smilax glabra, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca and Phellodendron chinense are mixed and extracted with an ethanol solution containing 0.2-0.8 wt% hydrochloric acid 1-3 times, each time for 1-2 hours. The extracts are combined and concentrated under reduced pressure at 55-65℃ to obtain the Chinese herbal extract. S3: Add ethanol to the Chinese herbal extract to a final concentration of 70-78%, let it stand at 0-5℃ for 20-26 hours, take the supernatant to recover the ethanol until there is no alcohol taste, add soybean lecithin and mix, homogenize and disperse and then dry to obtain phospholipid complex Chinese herbal extract powder. S4: Sulfobutyl ether-β-cyclodextrin is mixed with water to obtain an inclusion solution; S5: Mix the volatile oil from step S1 with the inclusion solution from step S4, shear emulsify for 3-6 minutes, stir and include for 5-7 hours, and freeze dry to obtain volatile oil microcapsule powder. S6: The phospholipid compound Chinese herbal extract powder, isomaltitol, and sodium octenyl succinate starch from step S3 are added to a fluidized bed and mixed. Then, 25wt%-35wt% ethyl cellulose aqueous dispersion is used as a binder for spray granulation and granulation to obtain granules. S7: The volatile oil microcapsule powder from step S5 is mixed with the raw granules from step S6 and granulated to obtain the final product.

7. The preparation method according to claim 6, characterized in that, In step S1, the total mass of Atractylodes lancea and Clematis chinensis is in a material-to-liquid ratio of 1g:5-10mL to water; the total mass of the dregs, Smilax glabra, Plantago asiatica, Polygonum cuspidatum, Dioscorea hypoglauca and Phellodendron chinense is in a material-to-liquid ratio of 1g:10-20mL to the ethanol solution; and the ethanol solution contains 55%-65% ethanol by mass.

8. The preparation method according to claim 6, characterized in that, In step S4, the mass-to-volume ratio of sulfobutyl ether-β-cyclodextrin to water is 1g:3-5mL; in step S5, the stirring and encapsulation temperature is 35-40℃.

9. The preparation method according to claim 6, characterized in that, In step S6, the parameters for spray granulation are: air inlet temperature 65-70℃, material temperature 45-50℃, and drying to moisture content ≤3.0%.

10. The use of Lingxian granules according to any one of claims 1-5 in the preparation of a medicament for treating gout.

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