Traditional Chinese medicine composition for reducing uric acid and application thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine pharmacy, and discloses a traditional Chinese medicine composition for reducing uric acid and application thereof, and the traditional Chinese medicine composition comprises the following components in parts by mass: 15-20 parts of ash bark, 20-25 parts of clerodendranthus spicatus, 18-22 parts of astragalus membranaceus, 12-15 parts of prepared polygonum multiflorum, 15-18 parts of rhizoma smilacis glabrae, 8-10 parts of ligusticum wallichii, 10-12 parts of roasted rhizoma atractylodis macrocephalae and 10-15 parts of salt-fried semen plantaginis. The preparation method comprises the three steps of segmented extraction, sustained-release pellet forming and preparation forming. The traditional Chinese medicine composition disclosed by the invention has the high-efficiency performance of reducing uric acid, protecting healthy qi and achieving long-term effect, and can regulate and control a uric acid metabolic pathway in a multi-target manner; the product can be widely applied to the fields of products for treating primary hyperuricemia and gout in a sustained-release period, products for improving hyperuricemia metabolic syndrome, health-care tea for hyperuricemia and high-risk people, gel products for relieving red, swollen and heat pain of joints in an acute attack period of gout and the like, and the preparation process is controllable and easy to industrialize.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine pharmaceutical technology, and more specifically, to a traditional Chinese medicine composition for lowering uric acid and its application. Background Technology

[0002] Hyperuricemia is a metabolic disease caused by purine metabolism disorder or uric acid excretion disorder, resulting in elevated blood uric acid levels (≥420 μmol / L). Long-term development can easily lead to gout, uric acid nephropathy, and even renal failure. It is also often accompanied by metabolic syndromes such as obesity and hyperlipidemia, making clinical needs urgent.

[0003] Existing traditional Chinese medicines for lowering uric acid have the following shortcomings: 1. They mainly focus on "clearing heat and promoting diuresis" while neglecting the core pathogenesis of "spleen and kidney deficiency," and long-term use can easily damage the body's vital energy; 2. They have a single target, mostly focusing on inhibiting xanthine oxidase (XOD), and lack synergistic regulation of uric acid excretion pathways (URAT1, GLUT9) and inflammatory pathways (NF-κB); 3. The dosage forms are mostly traditional decoctions or ordinary tablets, with low dissolution rate of effective ingredients and insufficient bioavailability (<30%).

[0004] Therefore, developing a traditional Chinese medicine composition and highly effective preparation that takes into account "lowering uric acid, protecting vital energy and long-lasting effect" and can regulate uric acid metabolism pathways at multiple targets is of great practical significance and has become the key to solving the shortcomings of existing technologies. Summary of the Invention

[0005] In view of this, the present invention proposes a traditional Chinese medicine composition for lowering uric acid and its application, aiming to solve the problems of insufficient pathogenesis adaptation, single target of action, and defects in formulation performance of current traditional Chinese medicine compositions for lowering uric acid.

[0006] This invention proposes a traditional Chinese medicine composition for lowering uric acid, wherein the composition comprises the following components in parts by weight: 15-20 parts of Fraxinus rhynchophylla, 20-25 parts of Orthosiphon aristatus, 18-22 parts of Astragalus membranaceus, 12-15 parts of processed Polygonum multiflorum, 15-18 parts of Smilax glabra, 8-10 parts of Ligusticum chuanxiong, 10-12 parts of stir-fried Atractylodes macrocephala, and 10-15 parts of salt-processed Plantago asiatica.

[0007] Furthermore, the prepared Polygonum multiflorum is prepared by steaming and processing with black bean juice, and the salt-roasted Plantago asiatica is a salt-roasted product obtained by stir-frying with salt water.

[0008] The preparation method of the traditional Chinese medicine composition includes the following steps: (1) Segmented extraction: Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum were added to water and refluxed for extraction. The aqueous extracts were combined. Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica were added to ethanol and ultrasonically extracted. The ethanol extract was recovered. The aqueous extract and ethanol extract were combined, concentrated under reduced pressure to obtain an extract, and spray-dried to obtain a dry extract powder. (2) Slow-release microcapsule forming: The dry extract powder is mixed with microcrystalline cellulose, sprayed into an ethanol solution, and then made into pellets; the pellets are coated with an HPMC K15M aqueous solution and dried to obtain slow-release microcapsules; (3) Formulation: The sustained-release microspheres are compressed into sustained-release tablets or filled into sustained-release capsules.

[0009] Furthermore, in step (1), the amount of water used is 7 to 10 times the total mass of Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum; the reflux extraction parameters are: temperature 90 to 100℃, time 1.5 to 2.5 h each time, and extraction times 1 to 3 times; the amount of ethanol used is 4 to 7 times the total mass of Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica; and the ultrasonic extraction parameters are: power 300 to 500 W, temperature 50 to 70℃, extraction times 2 to 4 times, and time 1 to 2 h each time.

[0010] Furthermore, the vacuum concentration parameters in step (1) are: vacuum degree -0.085~-0.095MPa, material temperature 45~55℃, stirring rate 50~80r / min, concentration key temperature 60~70℃, and relative density 1.25; the spray drying parameters are: atomization pressure 0.2~0.3MPa, inlet air temperature 180~200℃, outlet air temperature 80~90℃, feed rate 15~20mL / min, and particle size 150~180μm.

[0011] Furthermore, in step (2), the mass ratio of the dry extract powder to the microcrystalline cellulose is 1:2~4, the amount of ethanol used is 3~8% of the total mass of the dry extract powder and the microcrystalline cellulose, and the particle size of the pellets is 125~150μm.

[0012] Furthermore, the concentration of the HPMC K15M aqueous solution in step (2) is 5%, and the coating parameters are: inlet air temperature 45~55℃, outlet air temperature 30~40℃, and coating to a weight gain of 13~18%.

[0013] This invention also provides applications of the traditional Chinese medicine composition described in the above technical solution, wherein the specific applications include: (1) Application of the product in the treatment of primary hyperuricemia and gout during the sustained-release phase; (2) Application of products for improving hyperuricemia metabolic syndrome; (3) Application of health tea drinks in high-risk groups with high uric acid; (4) Application of topical gel products in relieving joint redness, swelling, heat and pain during acute gout attacks.

[0014] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention breaks through the traditional approach of "single heat-clearing and dampness-removing" and for the first time constructs a compound formula that "strengthens the spleen and kidneys and clears heat and removes blood stasis," which takes into account both lowering uric acid and protecting the body's vital energy. Long-term use of this medicine does not cause damage to the spleen and stomach.

[0015] This invention achieves synergistic regulation of multiple targets, including uric acid production, excretion, deposition, and inflammation, rather than simply inhibiting XOD.

[0016] This invention effectively improves the retention rate of components by employing segmented extraction and low-temperature vacuum concentration technology, enhances bioavailability and duration of efficacy through sustained-release microparticle technology, and extends the storage time of the formulation through spray drying powdering.

[0017] The traditional Chinese medicine composition of this invention can cover all scenarios of "treatment, prevention and local relief", and can be used in combination with Western medicine to reduce toxicity and enhance efficacy. It is suitable for people with kidney damage. Detailed Implementation

[0018] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0019] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included within this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0020] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0021] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0022] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0023] This invention proposes a traditional Chinese medicine composition for lowering uric acid, wherein the composition comprises the following components in parts by weight: 15-20 parts of Fraxinus rhynchophylla, 20-25 parts of Orthosiphon aristatus, 18-22 parts of Astragalus membranaceus, 12-15 parts of processed Polygonum multiflorum, 15-18 parts of Smilax glabra, 8-10 parts of Ligusticum chuanxiong, 10-12 parts of stir-fried Atractylodes macrocephala, and 10-15 parts of salt-processed Plantago asiatica.

[0024] In this invention, the traditional Chinese medicine composition is further preferably composed of the following components by weight: 16-20 parts of Fraxinus rhynchophylla, 22-25 parts of Orthosiphon aristatus, 20-22 parts of Astragalus membranaceus, 13-15 parts of processed Polygonum multiflorum, 16-18 parts of Smilax glabra, 9-10 parts of Ligusticum chuanxiong, 11-12 parts of stir-fried Atractylodes macrocephala, and 12-15 parts of salt-processed Plantago asiatica.

[0025] In this invention, the principal, assistant, adjuvant, and guide herbs are clearly distinguished: Astragalus membranaceus and stir-fried Atractylodes macrocephala are the principal herbs (to strengthen the spleen and benefit the kidneys), Fraxinus chinensis and Orthosiphon aristatus are the assistant herbs (to clear heat and promote diuresis), processed Polygonum multiflorum and Ligusticum chuanxiong are the adjuvant herbs (to resolve blood stasis and protect the kidneys), and Plantago asiatica is the guide herb (to guide the medicine downwards).

[0026] In this invention, Astragalus membranaceus is used to invigorate the spleen and replenish qi, protect renal tubules, and upregulate GLUT9 to promote uric acid secretion; Atractylodes macrocephala is used to invigorate the spleen and dry dampness, regulate intestinal flora, and reduce endogenous uric acid production; Fraxinus chinensis is used to clear heat and dry dampness, inhibit XOD=, and activate AMPK to promote excretion; Orthosiphon aristatus is used to promote diuresis and relieve strangury, downregulate URAT1 expression, and reduce renal tubular absorption; Polygonum multiflorum is used to tonify the liver and kidneys and remove blood stasis, inhibit the NF-κB pathway, and reduce IL-1β; Ligusticum chuanxiong is used to invigorate blood and promote qi circulation, improve renal microcirculation, and increase renal blood flow; Plantago asiatica is used to guide the medicine downward, increase urine volume, and accelerate uric acid excretion; Smilax glabra is used to detoxify and promote diuresis, reduce urate crystal deposition, and reduce joint crystallization rate.

[0027] The prepared Polygonum multiflorum described in this invention is prepared by steaming and processing with black bean juice, and the salt-roasted Plantago asiatica is a salt-roasted product obtained by stir-frying with salt water.

[0028] In this invention, the traditional Chinese medicine composition includes processed Polygonum multiflorum, which is processed by steaming with black bean juice. Raw Polygonum multiflorum contains free anthraquinones and agastrin, which can easily cause liver damage with long-term use, such as hepatocyte necrosis and elevated transaminase levels. Processing with black bean juice can significantly reduce toxicity through "component transformation," thereby significantly reducing hepatotoxicity and ensuring long-term medication safety. Black beans are "sweet and neutral in nature, entering the liver and kidney meridians," which is similar to Polygonum multiflorum, which is "bitter, sweet, astringent, and slightly warm, also entering the liver and kidney meridians." The properties and flavors of Polygonum multiflorum are compatible. Steaming with black bean juice can "guide the medicine to the meridians," enhancing the tonifying effects of processed Polygonum multiflorum. This perfectly matches the core pathogenesis of "spleen and kidney deficiency" in this compound. Steaming with black bean juice can change the physicochemical properties of Polygonum multiflorum, optimize the dissolution and storage stability of its effective components, support the efficiency of the "segmented extraction" process of this invention, and the processing of Polygonum multiflorum with black bean juice can enhance the anti-inflammatory effect by regulating inflammatory pathways. Furthermore, processed Polygonum multiflorum can also form precise combinations with other components to enhance the overall efficacy.

[0029] In this invention, the traditional Chinese medicine composition includes salt-processed plantain seed. The salt-processed plantain seed is a salt-processed product obtained by stir-frying with salt water. It can work synergistically with other components, including the "assistant herb" cat's whiskers: salt-processed plantain seed guides the medicine to the kidneys, assisting cat's whiskers (downregulating URAT1) to act more precisely on the renal tubules, enhancing the effect of "reducing uric acid reabsorption". It complements the "principal herb" astragalus: astragalus protects the kidneys and increases glomerular filtration rate, while salt-processed plantain promotes diuresis and accelerates the excretion of uric acid through urine. The two form a synergistic pathway of "protecting the kidneys and excreting uric acid", avoiding the drawbacks of "simple diuresis damaging the kidneys" or "simple kidney protection and insufficient uric acid excretion". It meets the goal of "multi-target regulation": salt-processed plantain seed promotes uric acid excretion through the dual pathway of "increasing urine volume (carrier) and downregulating URAT1 (pathway)", forming a full-chain regulation of "generation-excretion-deposition" with fraxinus bark (inhibiting XOD) and smilax glabra (dissolving crystals), strengthening the compound's uric acid-lowering effect.

[0030] The preparation method of the traditional Chinese medicine composition includes the following steps: (1) Segmented extraction: Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum were added to water and refluxed for extraction. The aqueous extracts were combined. Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica were added to ethanol and ultrasonically extracted. The ethanol extract was recovered. The aqueous extract and ethanol extract were combined, concentrated under reduced pressure to obtain an extract, and spray-dried to obtain a dry extract powder. (2) Slow-release microcapsule forming: The dry extract powder is mixed with microcrystalline cellulose, sprayed into an ethanol solution, and then made into pellets; the pellets are coated with an HPMC K15M aqueous solution and dried to obtain slow-release microcapsules; (3) Formulation: The sustained-release microspheres are compressed into sustained-release tablets or filled into sustained-release capsules.

[0031] In step (1) of this invention, the amount of water used is 7 to 10 times the total mass of Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum; the reflux extraction parameters are: temperature 90 to 100℃, time 1.5 to 2.5 h each time, and extraction times 1 to 3 times; the amount of ethanol used is 4 to 7 times the total mass of Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica; and the ultrasonic extraction parameters are: power 300 to 500 W, temperature 50 to 70℃, extraction times 2 to 4 times, and time 1 to 2 h each time.

[0032] In this invention, the amount of water used is further preferably 8 to 10 times the total mass of Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum; the reflux extraction parameters are: temperature 95 to 100°C, time 2 to 2.5 hours each time, and extraction times 2 to 3 times; the amount of ethanol used is 5 to 7 times the total mass of Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica; and the ultrasonic extraction parameters are: power 350 to 500W, temperature 55 to 70°C, extraction times 3 to 4 times, and time 1.5 to 2 hours each time.

[0033] This invention selects a distribution extraction process in the preparation method of the traditional Chinese medicine composition. The distribution extraction includes water extraction and alcohol extraction. The water extraction is a reflux extraction, in which the extract is continuously heated to boiling and the steam is condensed and refluxed to fully dissolve the water-soluble effective components in the above-mentioned medicinal materials. This is effective for water-soluble and heat-resistant polysaccharides and saponins in Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum, while avoiding carbonization of polysaccharide components due to excessively high temperatures. The alcohol extraction refers to ultrasonic extraction. Ethanol can improve the solubility of flavonoid components and enhance the dissolution effect of ultrasonic extraction. On the other hand, the temperature is below the boiling point of ethanol, which can avoid the rapid evaporation of ethanol during the extraction process, reduce solvent loss, and prevent high temperature from damaging the heat-sensitive core component of Orthosiphon aristatus, rosmarinic acid, thus ensuring the activity of effective components. This is effective for alcohol-soluble and heat-sensitive flavonoids and glycosides in Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica.

[0034] The vacuum concentration parameters in step (1) of this invention are preferably: vacuum degree -0.085~-0.095MPa, material temperature 45~55℃, stirring rate 50~80r / min, concentration focus temperature 60~70℃, and relative density 1.25. More preferably, the vacuum degree -0.088~-0.095MPa, material temperature 50~55℃, stirring rate 55~80r / min, and concentration focus temperature 60~65℃. The spray drying parameters are preferably: atomization pressure 0.2~0.3MPa, inlet air temperature 180~200℃, outlet air temperature 80~90℃, feed rate 15~20mL / min, and particle size 150~180μm. More preferably, the atomization pressure 0.25~0.3MPa, inlet air temperature 185~200℃, outlet air temperature 85~90℃, feed rate 16~20mL / min, and particle size 160~180μm.

[0035] In this invention, the preparation method of the traditional Chinese medicine composition selects a vacuum concentration process. The vacuum concentration plays a crucial role in the process, protecting heat-sensitive components under low-temperature conditions, ensuring the core efficacy of uric acid-lowering drugs, improving concentration efficiency, and shortening the heating time of materials. It can also precisely control the quality of the extract, adapt to subsequent processes, reduce component wall adhesion loss, improve material utilization, and ensure stable and controllable parameters, making it suitable for industrial production.

[0036] This invention selects spray drying as a method for preparing traditional Chinese medicine compositions. Spray drying can efficiently retain heat-sensitive active ingredients through instantaneous drying, ensuring the efficacy of lowering uric acid. The spray-dried powder is a loose spherical particle that does not require pulverization. Its powder has good flowability, making it suitable for industrial granulation of sustained-release microcapsules. Furthermore, the low moisture content of the spray-dried powder can effectively prevent the oxidation of active ingredients due to moisture absorption during storage, thus extending the shelf life of the preparation. In addition, spray drying has a high degree of automation, allowing for continuous production and making it suitable for large-scale production.

[0037] In step (2) of the present invention, the mass ratio of dry extract powder to microcrystalline cellulose is preferably 1:2~4, more preferably 1:3~4, the amount of ethanol is preferably 3~8% of the total mass of dry extract powder and microcrystalline cellulose, more preferably 5~8%, and the particle size of the pellets is preferably 125~150μm, more preferably 130~150μm.

[0038] In this invention, microcrystalline cellulose is added to the preparation method of the traditional Chinese medicine composition. The microcrystalline cellulose is a pharmaceutical excipient added separately. On the one hand, it acts as a "filler" to improve the flowability and compressibility of the dry extract powder. Traditional Chinese medicine extracts are often difficult to granulate due to their high viscosity and strong hygroscopicity, and microcrystalline cellulose can solve this problem. On the other hand, it acts as a "forming agent" to synergistically form uniform 125-150μm pellets with the dry extract powder, providing a stable core material basis for subsequent fluidized bed coating (forming a sustained-release layer) without affecting the release characteristics of the active ingredients of the traditional Chinese medicine.

[0039] This invention does not limit the specific type of microcrystalline cellulose; any microcrystalline cellulose known to those skilled in the art can be used. In the embodiments of this invention, pharmaceutical grade PH102 microcrystalline cellulose is used.

[0040] The concentration of the HPMC K15M aqueous solution in step (2) of the present invention is 5%, and the coating parameters are preferably: inlet air temperature 45~55℃, outlet air temperature 30~40℃, coating to a weight gain of 13~18%, and more preferably inlet air temperature 50~55℃, outlet air temperature 35~40℃, coating to a weight gain of 15~18%.

[0041] In this invention, HPMC K15M aqueous solution is selected as the coating solution. On the one hand, HPMC K15M aqueous solution is a high-viscosity pharmaceutical-grade hydroxypropyl methylcellulose, which is a semi-finished cellulose ether excipient that is not digested and absorbed in the body. On the other hand, it can achieve sustained drug release and ensure the quality of the formulation. Its sustained-release effect allows the drug to be released slowly in the intestine, prolonging the absorption time.

[0042] The sustained-release microgranules mentioned in step (2) of this invention are active carriers for traditional Chinese medicine composition preparations. They refer to spherical or near-spherical microparticles with a diameter typically 0.5-1.5 mm, prepared through a specific process. Their core function is to slowly release the effective components of traditional Chinese medicine at a preset rate, achieving the goal of long-lasting uric acid reduction and reducing the frequency of medication. Furthermore, the sustained-release microgranules of this invention have a double-layer structure consisting of an inner core material and an outer coating layer. The core material can carry all the effective components for lowering uric acid. Microcrystalline cellulose serves as a filler, improving the flowability of the core material and ensuring uniform granulation. The outer coating layer forms a dense gel skeleton, controlling the... The slow release of the active ingredient isolates external humidity and oxygen, protecting the heat-sensitive components in the core material. The sustained-release microcapsules solve the pain points of traditional Chinese medicine preparations, such as "short duration of action, low bioavailability, and high frequency of administration." Through "precise sustained release and stable absorption," this uric acid-lowering compound can exert the advantages of "multi-target synergistic" efficacy in inhibiting production, promoting excretion, and anti-inflammatory and kidney-protecting effects, while also improving patient medication compliance. It is especially suitable for people with hyperuricemia who need long-term management. The release rate of the sustained-release microcapsules of this invention should meet the following requirements: 20-30% release in 1 hour, 60-70% release in 6 hours, and ≥90% release in 12 hours.

[0043] This invention also provides applications of the traditional Chinese medicine composition described in the above technical solution, wherein the specific applications include: (1) Application of the product in the treatment of primary hyperuricemia and gout during the sustained-release phase; (2) Application of products for improving hyperuricemia metabolic syndrome; (3) Application of health tea drinks in high-risk groups with high uric acid; (4) Application of topical gel products in relieving joint redness, swelling, heat and pain during acute gout attacks.

[0044] The health tea beverage described in this invention is a tea bag, and the external gel contains 5% dry extract powder.

[0045] In this invention, unless otherwise specified, all raw materials required for preparation are commercially available products well known to those skilled in the art.

[0046] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0047] Example 1 Ingredients: 16 parts Fraxinus rhizome, 22 parts Orthosiphon aristatus, 20 parts Astragalus membranaceus, 13 parts processed Polygonum multiflorum, 16 parts Smilax glabra, 9 parts Ligusticum chuanxiong, 11 parts stir-fried Atractylodes macrocephala, 12 parts salt-processed Plantago asiatica; the processed Polygonum multiflorum is prepared by steaming and processing with black bean juice, and the salt-processed Plantago asiatica is obtained by stir-frying with salt water. Preparation method: (1) Segmented extraction: Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum were added to 8 times the amount of water and refluxed twice at 95℃ for 2 hours each time. The aqueous extract was then combined. Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica were added to 5 times the amount of ethanol and ultrasonically extracted three times at 350W and 55℃ for 1.5 hours each time. The ethanol extract was then recovered. The aqueous and ethanol extracts were combined and concentrated under reduced pressure to 60℃ at -0.088MPa, material temperature 50℃, and stirring rate 55r / min to obtain an extract. The extract was then spray-dried at an atomization pressure of 0.25MPa, inlet air temperature of 185℃, outlet air temperature of 85℃, and feed rate of 16mL / min to obtain a 160μm dry extract powder. (2) Sustained-release microcapsule forming: The dry extract powder and pharmaceutical grade PH102 microcrystalline cellulose are mixed at a mass ratio of 1:3. After spraying in an ethanol solution of 5% of the total mass of the dry extract powder and microcrystalline cellulose, 130μm pellets are formed. The pellets are coated with a 5% HPMC K15M aqueous solution to achieve a weight gain of 15%. After drying at an inlet air temperature of 50℃ and an outlet air temperature of 35℃, sustained-release microcapsules are obtained. (3) Formulation: The sustained-release microspheres are compressed into sustained-release tablets or filled into sustained-release capsules.

[0048] Example 2 Ingredients: 20 parts Fraxinus rhizome, 25 parts Orthosiphon aristatus, 22 parts Astragalus membranaceus, 15 parts processed Polygonum multiflorum, 18 parts Smilax glabra, 10 parts Ligusticum chuanxiong, 12 parts stir-fried Atractylodes macrocephala, 15 parts salt-processed Plantago asiatica; the processed Polygonum multiflorum is prepared by steaming and processing with black bean juice, and the salt-processed Plantago asiatica is obtained by stir-frying with salt water. Preparation method: (1) Segmented extraction: Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum were added to 10 times the amount of water and refluxed for 3 times at 100℃ for 2.5h each time. The aqueous extract was then combined. Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica were added to 7 times the amount of ethanol and ultrasonically extracted for 4 times at 500W and 70℃ for 2h each time. The ethanol extract was then recovered. The aqueous extract and ethanol extract were combined and concentrated under reduced pressure to 65℃ at -0.095MPa, material temperature 55℃, and stirring rate 80r / min to obtain an extract. The extract was then spray-dried at a misting pressure of 0.3MPa, inlet air temperature of 200℃, outlet air temperature of 90℃, and feed rate of 20mL / min to obtain a 180μm dry extract powder. (2) Sustained-release microcapsule forming: The dry extract powder and pharmaceutical grade PH102 microcrystalline cellulose are mixed at a mass ratio of 1:4. After spraying the mixture into an ethanol solution containing 8% of the total mass of the dry extract powder and microcrystalline cellulose, 150μm pellets are formed. The pellets are coated with a 5% HPMC K15M aqueous solution to achieve a weight gain of 18%. After drying at an inlet air temperature of 55℃ and an outlet air temperature of 40℃, sustained-release microcapsules are obtained. (3) Formulation: The sustained-release microspheres are compressed into sustained-release tablets or filled into sustained-release capsules.

[0049] Example 3 Ingredients: 18 parts Fraxinus rhizome, 23 parts Orthosiphon aristatus, 21 parts Astragalus membranaceus, 14 parts processed Polygonum multiflorum, 17 parts Smilax glabra, 9 parts Ligusticum chuanxiong, 11 parts stir-fried Atractylodes macrocephala, 14 parts salt-processed Plantago asiatica; the processed Polygonum multiflorum is prepared by steaming and processing with black bean juice, and the salt-processed Plantago asiatica is obtained by stir-frying with salt water. Preparation method: (1) Segmented extraction: Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum were added to 9 times the amount of water and refluxed twice at 95℃ for 2 hours each time. The aqueous extract was then combined. Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica were added to 6 times the amount of ethanol and ultrasonically extracted three times at 350W and 60℃ for 1.5 hours each time. The ethanol extract was then recovered. The aqueous and ethanol extracts were combined and concentrated under reduced pressure to 60℃ at -0.090MPa, material temperature 50℃, and stirring rate 65r / min to obtain an extract. The extract was then spray-dried at an atomization pressure of 0.25MPa, inlet air temperature of 190℃, outlet air temperature of 85℃, and feed rate of 18mL / min to obtain a 170μm dry extract powder. (2) Sustained-release microcapsule forming: The dry extract powder and pharmaceutical grade PH102 microcrystalline cellulose are mixed at a mass ratio of 1:3, and then sprayed into an ethanol solution of 5% of the total mass of the dry extract powder and microcrystalline cellulose to form 140μm pellets; the pellets are coated with a 5% HPMC K15M aqueous solution to achieve a weight gain of 16%, and dried under the conditions of an inlet air temperature of 50℃ and an outlet air temperature of 35℃ to obtain sustained-release microcapsules; (3) Formulation: The sustained-release microspheres are compressed into sustained-release tablets or filled into sustained-release capsules.

[0050] Effect detection: Experimental subjects: Eight-week-old male SD rats weighing 220-250g were used to establish a hyperuricemia model by daily gavage administration of potassium oxonate (200mg / kg) and adenine (100mg / kg) for 7 consecutive days. Success was defined as serum uric acid ≥550μmol / L in the experimental subjects. Grouping and administration: Ten rats were divided into four groups: a control group was administered physiological saline by gavage; the Example 1 group was administered Example 1 sustained-release tablet suspension by gavage at a dose of 1 g / kg, containing the active ingredient equivalent to 10 g / kg of crude drug; the Example 2 group was administered Example 2 sustained-release tablet suspension by gavage at a dose of 1 g / kg, containing the active ingredient equivalent to 10 g / kg of crude drug; and the Example 3 group was administered Example 3 sustained-release tablet suspension by gavage at a dose of 1 g / kg, containing the active ingredient equivalent to 10 g / kg of crude drug. Administration was continued for 14 days, once daily, and relevant indicators were measured 24 hours after the last administration.

[0051] The results of uric acid reduction and organ protection tests in Examples 1-3 and the control group are shown in Table 1 below: Table 1. Detection of Uric Acid Lowering and Organ Protection

[0052] The sustained-release performance test results of Examples 1-3 are shown in Table 2 below: Table 2 Results of sustained-release performance testing in Examples 1-3

[0053] The bioavailability and safety test results of Examples 1-3 are shown in Table 3 below: Table 3. Bioavailability and safety test results of Examples 1-3

[0054] In summary, compared with the control group that did not use the traditional Chinese medicine composition prepared by this invention, the traditional Chinese medicine composition products prepared in Examples 1-3 can all reduce uric acid, with a reduction in urinary microalbumin, no liver or kidney damage, and meet the standards for long-term medication. Examples 2 and 3 also meet the needs of gout remission. Furthermore, the test results of Examples 1-3 show that Example 1 is suitable for patients with mild to moderate hyperuricemia, Example 2 is suitable for patients with severe hyperuricemia and mild kidney damage, and the product of Example 3 is suitable for patients with hyperuricemia metabolic syndrome who require long-term medication.

[0055] The above embodiments are merely preferred embodiments of the present invention and are not intended to limit the present invention. The scope of protection of the present invention is determined by the appended claims.

[0056] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the specific implementation of the present invention. Any modifications or equivalent substitutions that do not depart from the spirit and scope of the present invention should be covered within the scope of protection of the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for lowering uric acid, characterized in that, The traditional Chinese medicine composition contains the following components in parts by weight: 15-20 parts of Fraxinus rhynchophylla, 20-25 parts of Orthosiphon aristatus, 18-22 parts of Astragalus membranaceus, 12-15 parts of processed Polygonum multiflorum, 15-18 parts of Smilax glabra, 8-10 parts of Ligusticum chuanxiong, 10-12 parts of stir-fried Atractylodes macrocephala, and 10-15 parts of salt-processed Plantago asiatica.

2. The traditional Chinese medicine composition for lowering uric acid according to claim 1, characterized in that, The prepared Polygonum multiflorum is prepared by steaming and processing with black bean juice, and the salt-roasted Plantago asiatica is a salt-roasted product obtained by stir-frying with salt water.

3. A method for preparing the traditional Chinese medicine composition according to any one of claims 1-2, characterized in that, Includes the following steps: (1) Segmented extraction: Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum were added to water and refluxed for extraction. The aqueous extracts were combined. Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica were added to ethanol and ultrasonically extracted. The ethanol extract was recovered. The aqueous extract and ethanol extract were combined, concentrated under reduced pressure to obtain an extract, and spray-dried to obtain a dry extract powder. (2) Slow-release microcapsule forming: The dry extract powder is mixed with microcrystalline cellulose, sprayed into an ethanol solution, and then made into pellets; the pellets are coated with an HPMC K15M aqueous solution and dried to obtain slow-release microcapsules; (3) Formulation: The sustained-release microspheres are compressed into sustained-release tablets or filled into sustained-release capsules.

4. The method for preparing the traditional Chinese medicine composition for lowering uric acid according to claim 3, characterized in that, The amount of water used in step (1) is 7 to 10 times the total mass of Astragalus membranaceus, stir-fried Atractylodes macrocephala, and processed Polygonum multiflorum; the reflux extraction parameters are: temperature 90 to 100℃, time 1.5 to 2.5 h each time, and extraction times 1 to 3 times; the amount of ethanol used is 4 to 7 times the total mass of Fraxinus chinensis, Orthosiphon aristatus, Ligusticum chuanxiong, Smilax glabra, and salt-processed Plantago asiatica; the ultrasonic extraction parameters are: power 300 to 500 W, temperature 50 to 70℃, extraction times 2 to 4 times, and time 1 to 2 h each time.

5. The method for preparing the traditional Chinese medicine composition for lowering uric acid according to claim 3, characterized in that, The vacuum concentration parameters in step (1) are: vacuum degree -0.085~-0.095MPa, material temperature 45~55℃, stirring rate 50~80r / min, concentration temperature 60~70℃, and relative density 1.25; the spray drying parameters are: atomization pressure 0.2~0.3MPa, inlet air temperature 180~200℃, outlet air temperature 80~90℃, feed rate 15~20mL / min, and particle size 150~180μm.

6. The method for preparing the traditional Chinese medicine composition for lowering uric acid according to claim 3, characterized in that, In step (2), the mass ratio of dry extract powder to microcrystalline cellulose is 1:2~4, the amount of ethanol used is 3~8% of the total mass of dry extract powder and microcrystalline cellulose, and the particle size of the pellets is 125~150μm.

7. The method for preparing the traditional Chinese medicine composition for lowering uric acid according to claim 3, characterized in that, The concentration of the HPMC K15M aqueous solution in step (2) is 5%, and the coating parameters are: inlet air temperature 45~55℃, outlet air temperature 30~40℃, and coating to a weight gain of 13~18%.

8. The application of a traditional Chinese medicine composition for lowering uric acid as described in any one of claims 1 to 2, characterized in that, The application includes: (1) Application of the product in the treatment of primary hyperuricemia and gout during the sustained-release phase; (2) Application of products for improving hyperuricemia metabolic syndrome; (3) Application of health tea drinks in high-risk groups with high uric acid; (4) Application of topical gel products in relieving joint redness, swelling, heat and pain during acute gout attacks.

Images