Traditional Chinese medicine composition for treating gouty nephropathy, pharmaceutical preparation and preparation method thereof

Abstract

The invention provides a traditional Chinese medicine composition for treating gouty nephropathy, a pharmaceutical preparation and a preparation method thereof, and belongs to the technical field of medicines. The traditional Chinese medicine composition for treating gouty nephropathy comprises the following components: astragalus membranaceus, codonopsis pilosula, cassia twig, eucommia ulmoides, dogwood, semen cuscutae, bighead atractylodes rhizome, rhizoma atractylodis, pericarpium citri reticulatae, poria cocos, yam rhizome and rhizoma alismatis. The traditional Chinese medicine composition and the pharmaceutical preparation provided by the invention have the effects of tonifying spleen and kidney, warming phlegm and fluid retention, and discharging turbidity and dredging collaterals, and have a good treatment effect on gouty nephropathy.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine, and particularly relates to a traditional Chinese medicine composition for treating gouty nephropathy, a pharmaceutical preparation and a preparation method thereof. Background Art

[0002] Gouty nephropathy, also known as chronic uric acid nephropathy, is caused by excessive production or reduced excretion of blood uric acid, resulting in supersaturation of urate in the blood. Deposition of urate crystals in the kidneys causes kidney damage. In severe cases, gouty nephropathy can progress to renal failure. Gouty nephropathy is a complication caused by the further development of hyperuricemia. Hyperuricemia itself has mild clinical symptoms and slow disease progression. The damage to the kidneys in the early stage is not obvious and is easily ignored by patients. However, hyperuricemia not only accelerates kidney damage and leads to abnormal renal function, but also causes other complications such as cardiovascular and cerebrovascular diseases, which is extremely unfavorable for the treatment and prognosis of patients.

[0003] According to the traditional Chinese medicine clinical pathway and traditional Chinese medicine diagnosis and treatment plan (2017 edition) for gouty nephropathy (uric acid nephropathy) issued by the State Administration of Traditional Chinese Medicine, the traditional Chinese medicine syndrome differentiation of gouty nephropathy is: the main symptoms such as turbid urine, edema, frequent urination at night, fatigue, soreness and pain in the waist, joint swelling or immobility, chest and epigastric stuffiness, and sticky feeling in the mouth. The western medicine diagnostic criteria are: male blood uric acid > 417 μmol / L (7.0 mg / dL), female blood uric acid > 357 μmol / L (6.0 mg / mL); in those with normal renal function, urinary uric acid secretion exceeds 800 mg / d (418 mmol / d), and proteinuria.

[0004] Based on the current diagnosis and treatment plan, for patients with gouty nephropathy accompanied by gout, non-drug treatment and uric acid-lowering treatment should be actively given in the early stage. First-line uric acid-lowering drugs include drugs that inhibit uric acid production (allopurinol and febuxostat), and drugs that promote uric acid excretion (benzbromarone and probenecid) can be alternative drugs. However, the benefits of uric acid-lowering treatment on the kidneys also need to be confirmed by more high-quality, large-sample RCTs. Therefore, there is an urgent need to develop drugs for gouty nephropathy to relieve the pain of patients.

[0005] Clinical and experimental studies on many traditional Chinese medicines have shown that traditional Chinese medicine has good effects in relieving clinical symptoms and delaying kidney damage. Clinical experts in traditional Chinese medicine believe that the root cause of chronic uric acid nephropathy is the deficiency of the spleen and kidney, while damp-heat, phlegm-turbidity, blood stasis, etc. are the excess syndromes. Looking at its pathogenesis, it is mostly due to congenital endowment deficiency, and later excessive eating of fatty and sweet foods and excessive drinking, which damage the spleen and stomach. The spleen is responsible for replenishing the congenital endowment, and the transportation and transformation of water and grain essence are abnormal. Over time, it affects the kidney, resulting in kidney qi deficiency. When the spleen and kidney qi are deficient, the transformation of water and dampness is insufficient, and phlegm-dampness accumulates and blocks the meridians, which can cause joint swelling and pain, limb heaviness or numbness, and difficulty in flexion and extension. The imbalance of qi, blood, yin and yang, and the accumulation of water, dampness and phlegm, the pathogenic factors become more and more severe. Therefore, in the treatment, traditional Chinese medicine treats chronic uric acid nephropathy by formulating prescriptions and dispensing medicines based on the main pathogenesis of spleen and kidney qi deficiency combined with phlegm-turbidity blocking the interior, and pays attention to the method of treating both the symptoms and the root causes. Summary of the Invention

[0006] Aiming at the deficiencies of the existing technology, the purpose of the present invention is to provide a traditional Chinese medicine composition, a pharmaceutical preparation and a preparation method thereof for treating gouty nephropathy. The traditional Chinese medicine composition and the pharmaceutical preparation have the functions of strengthening the spleen and tonifying the kidney, warming and resolving phlegm-fluid, and discharging turbidity and dredging collaterals, and have good therapeutic effects on gouty nephropathy.

[0007] To achieve this purpose, the present invention adopts the following technical solutions:

[0008] In the first aspect, the present invention provides a traditional Chinese medicine composition for treating gouty nephropathy, which comprises the following components:

[0009] Astragalus membranaceus, Codonopsis pilosula, Cinnamomum cassia, Eucommia ulmoides, Cornus officinalis, Cuscuta chinensis, Atractylodes macrocephala, Atractylodes lancea, Citrus reticulata Blanco, Poria cocos, Dioscorea septemloba and Alisma orientale.

[0010] In some preferred embodiments of the present invention, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0011] 5-15 parts of Astragalus membranaceus, 3-9 parts of Codonopsis pilosula, 4-12 parts of Cinnamomum cassia, 4-12 parts of Eucommia ulmoides, 4-12 parts of Cornus officinalis, 4-12 parts of Cuscuta chinensis, 4-12 parts of Atractylodes macrocephala, 3-9 parts of Atractylodes lancea, 4-12 parts of Citrus reticulata Blanco, 3-9 parts of Poria cocos, 3-9 parts of Dioscorea septemloba and 2.5-7.5 parts of Alisma orientale.

[0012] Among them, the parts by weight of Astragalus membranaceus can be any value within the range of 5-15 parts, for example, it can be 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts, 12 parts, 12.5 parts, 13 parts, 13.5 parts, 14 parts, 14.5 parts or 15 parts, etc.

[0013] The weight parts of Codonopsis pilosula can be any value within the range of 3 - 9 parts, for example, it can be 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts or 9 parts, etc.

[0014] The weight parts of Cinnamomum cassia can be any value within the range of 4 - 12 parts, for example, it can be 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts or 12 parts, etc.

[0015] The weight parts of Eucommia ulmoides can be any value within the range of 4 - 12 parts, for example, it can be 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts or 12 parts, etc.

[0016] The weight parts of Cornus officinalis can be any value within the range of 4 - 12 parts, for example, it can be 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts or 12 parts, etc.

[0017] The weight parts of Cuscuta chinensis can be any value within the range of 4 - 12 parts, for example, it can be 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts or 12 parts, etc.

[0018] The weight parts of Atractylodes macrocephala can be any value within the range of 4 - 12 parts, for example, it can be 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts or 12 parts, etc.

[0019] The weight parts of Atractylodes lancea can be any value within the range of 3 - 9 parts, for example, it can be 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts or 9 parts, etc.

[0020] The weight parts of Citrus reticulata Blanco can be any value within the range of 4 - 12 parts, for example, it can be 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts or 12 parts, etc.

[0021] The weight parts of Poria cocos can be any value within the range of 3 - 9 parts, for example, it can be 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts or 9 parts, etc.

[0022] The weight parts of Dioscorea septemloba Thunb. can be any value within the range of 3 - 9 parts, for example, it can be 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts or 9 parts, etc.

[0023] The weight parts of Alisma orientale (Sam.) Juz. can be any value within the range of 2.5 - 7.5 parts, for example, it can be 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts or 7.5 parts, etc.

[0024] In some preferred embodiments of the present invention, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0025] Astragalus membranaceus (Fisch.) Bunge 8 - 12 parts, Codonopsis pilosula (Franch.) Nannf. 4.5 - 7.5 parts, Cinnamomum cassia Presl 6 - 10 parts, Eucommia ulmoides Oliv. 6 - 10 parts, Cornus officinalis Sieb. et Zucc. 6 - 10 parts, Cuscuta chinensis Lam. 6 - 10 parts, Atractylodes macrocephala Koidz. 6 - 10 parts, Atractylodes lancea (Thunb.) DC. 4.5 - 7.5 parts, Citrus reticulata Blanco 6 - 10 parts, Poria cocos 4.5 - 7.5 parts, Dioscorea septemloba Thunb. 4.5 - 7.5 parts and Alisma orientale (Sam.) Juz. 4 - 6 parts.

[0026] In some preferred embodiments of the present invention, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0027] Astragalus membranaceus (Fisch.) Bunge 10 parts, Codonopsis pilosula (Franch.) Nannf. 6 parts, Cinnamomum cassia Presl 8 parts, Eucommia ulmoides Oliv. 8 parts, Cornus officinalis Sieb. et Zucc. 8 parts, Cuscuta chinensis Lam. 8 parts, Atractylodes macrocephala Koidz. 8 parts, Atractylodes lancea (Thunb.) DC. 6 parts, Citrus reticulata Blanco 8 parts, Poria cocos 6 parts, Dioscorea septemloba Thunb. 6 parts and Alisma orientale (Sam.) Juz. 5 parts.

[0028] Through the scientific compatibility of the above traditional Chinese medicine components, the present invention obtains a traditional Chinese medicine composition with good therapeutic effect on gouty nephropathy. The compatibility mechanism of this traditional Chinese medicine composition is as follows:

[0029] Astragalus membranaceus in this formula is sweet in flavor and slightly warm in nature, and pertains to the lung and spleen meridians, with the effects of invigorating qi to lift yang and promoting qi circulation to relieve obstruction; Codonopsis pilosula is sweet in flavor and neutral in nature, and pertains to the spleen and lung meridians, with the effect of strengthening the spleen and nourishing the lung; Cuscuta chinensis is pungent, sweet in flavor and neutral in nature, and pertains to the liver, kidney and spleen meridians, with the effects of tonifying the liver and kidney and astringing essence to reduce urination. Astragalus membranaceus, Codonopsis pilosula and Cuscuta chinensis are the main herbs for treating the syndrome of qi deficiency of the spleen and kidney in this syndrome, and together they are the sovereign herbs. Cinnamon twig is pungent, sweet in flavor and warm in nature, and pertains to the heart, lung and bladder meridians, with the effects of warming and dredging the meridians and assisting yang to transform qi; Eucommia ulmoides can tonify the liver and kidney and strengthen the bones and muscles, and is used for soreness and weakness of the waist and knees; Atractylodes macrocephala can strengthen the spleen and replenish qi, dry dampness and promote diuresis, and is used for poor appetite due to spleen deficiency. Cinnamon twig, Eucommia ulmoides and Atractylodes macrocephala together are the ministerial herbs, enhancing the effect of the sovereign herbs in strengthening the spleen and tonifying the kidney. Atractylodes lancea, Tangerine peel and Poria cocos all have the effect of strengthening the spleen. At the same time, tangerine peel also has the effect of drying dampness and resolving phlegm; Dioscorea septemloba can promote diuresis and remove turbidity, dispel wind and relieve obstruction, and is used for gonorrhea with turbid discharge, leukorrhagia, joint discomfort and pain in the waist and knees. Atractylodes lancea, tangerine peel, Poria cocos and Dioscorea septemloba together are the adjuvant herbs, enhancing the effect of the sovereign and ministerial herbs in strengthening the spleen and tonifying the kidney, and at the same time having the effects of resolving phlegm and removing turbidity to treat joint discomfort. Alisma orientale is the guiding herb, which pertains to the kidney and bladder meridians, promoting diuresis and percolating dampness, transforming turbidity, and providing an outlet for phlegm-fluid and damp-turbidity qi.

[0030] The functions and indications of the traditional Chinese medicine composition provided by the present invention are: strengthening the spleen and tonifying the kidney, warming and resolving phlegm-fluid, purging turbidity and dredging the collaterals. It is used for the syndrome of qi deficiency of the spleen and kidney and internal obstruction of phlegm-turbidity, manifested as sallow or yellowish complexion, soreness and weakness of the waist and knees, poor appetite; lassitude, lower limb edema, tastelessness in the mouth and no desire to drink, frequent urination or nocturia, repeated occurrence of turbid urine; joint swelling and pain without redness, heaviness or numbness of the limbs, difficulty in flexion and extension; dizziness and heaviness of the head, stuffiness and fullness in the chest and epigastrium, loss of appetite and nausea, dry mouth without desire to drink, sticky feeling in the mouth, coughing up white sticky phlegm; pale and plump tongue with tooth marks, thick and greasy white coating on the tongue, slippery or string-like pulse; those with gouty nephropathy showing the above syndromes.

[0031] In a second aspect, the present invention provides a pharmaceutical preparation for treating gouty nephropathy, and the pharmaceutical preparation contains the active ingredients of the traditional Chinese medicine composition described in the first aspect.

[0032] In some embodiments of the present invention, the pharmaceutical preparation further includes excipients.

[0033] In some embodiments of the present invention, the excipients include one or more of sucralose, DL-malic acid and dextrin;

[0034] In some embodiments of the present invention, the dosage form of the pharmaceutical preparation is tablets, capsules, granules or oral liquids.

[0035] In a third aspect, the present invention provides a preparation method of the pharmaceutical preparation described in the second aspect, and the preparation method includes the following steps:

[0036] (1) Performing water extraction on the traditional Chinese medicine composition described in the first aspect to obtain a water extract;

[0037] (2) Preparing the water extract into the dosage form of the pharmaceutical preparation.

[0038] In some embodiments of the present invention, the steps of water extraction in step (1) include: soaking the traditional Chinese medicine composition in water for 1 - 3 h (for example, it can be 1 h, 1.1 h, 1.2 h, 1.3 h, 1.4 h or 1.5 h, etc.), then decocting at least 3 times (for example, it can be 3 times, 4 times, 5 times or 6 times, etc.), each time for 1 - 3 h (for example, it can be 1 h, 1.1 h, 1.2 h, 1.3 h, 1.4 h or 1.5 h, etc.), filtering the decoction liquid, combining the filtrates to obtain the water extract. However, the present invention is not limited to the listed values, and other unlisted values within this range are equally applicable.

[0039] In some embodiments of the present invention, in the water extraction of step (1), the total mass of water is 15 - 30 times the mass of the traditional Chinese medicine composition; for example, it can be 15 times, 16 times, 18 times, 20 times, 22 times, 23 times, 25 times, 26 times, 28 times or 30 times, etc. However, the present invention is not limited to the listed values, and other unlisted values within this range are equally applicable.

[0040] In some embodiments of the present invention, the steps of preparing the water extract into the dosage form of the pharmaceutical preparation include: concentrating the water extract into a clear paste with a relative density of 1.09 - 1.12 (for example, it can be 1.09, 1.10, 1.11 or 1.12, etc.) at 50 °C; adding ethanol to make the ethanol content 65 - 75 wt% (for example, it can be 65 wt%, 66 wt%, 68 wt%, 70 wt%, 72 wt%, 73 wt% or 75 wt%, etc.), standing for 12 - 24 h (for example, it can be 12 h, 13 h, 15 h, 16 h, 18 h, 20 h, 22 h or 24 h, etc.), taking the supernatant and recovering ethanol, and then concentrating it into a thick paste with a relative density of 1.15 - 1.20 (for example, it can be 1.15, 1.16, 1.17, 1.18, 1.19 or 1.20, etc.) at 50 °C; drying it into a dry extract, pulverizing to obtain a dry extract powder; mixing the dry extract powder with sucralose, DL - malic acid and dextrin to make a granule. However, the present invention is not limited to the listed values, and other unlisted values within this range are equally applicable.

[0041] In some embodiments of the present invention, the concentration method is: under the conditions of a temperature of 65 - 70 °C (for example, it can be 65 °C, 66 °C, 67 °C, 68 °C, 69 °C or 70 °C, etc.) and a vacuum degree of - 0.05 to - 0.07 MPa (for example, it can be - 0.05 MPa, - 0.055 MPa, - 0.06 MPa, - 0.065 MPa or - 0.07 MPa, etc.), concentrating under reduced pressure. However, the present invention is not limited to the listed values, and other unlisted values within this range are equally applicable.

[0042] In some embodiments of the present invention, the drying method is as follows: under the conditions of a temperature of 65 - 70 °C (such as 65 °C, 66 °C, 67 °C, 68 °C, 69 °C or 70 °C, etc.) and a vacuum degree of -0.06 to -0.08 MPa (such as -0.06 MPa, -0.065 MPa, -0.07 MPa, -0.075 MPa or -0.08 MPa, etc.), vacuum drying is carried out. However, the present invention is not limited to the listed values, and other unlisted values within this range are equally applicable.

[0043] Compared with the prior art, the present invention has the following beneficial effects:

[0044] By scientifically combining Astragalus membranaceus, Codonopsis pilosula, Cinnamomum cassia, Eucommia ulmoides, Cornus officinalis, Cuscuta chinensis, Atractylodes macrocephala, Atractylodes lancea, Citrus reticulata Blanco, Poria cocos, Dioscorea septemloba Thunb. and Alisma orientale, the present invention obtains a traditional Chinese medicine composition and a pharmaceutical preparation with good therapeutic effects on gouty nephropathy. The traditional Chinese medicine composition and the pharmaceutical preparation can play the roles of strengthening the spleen and tonifying the kidney, warming and resolving phlegm-fluid retention, and purging turbidity and dredging collaterals; they can be used for the syndrome of qi deficiency of the spleen and kidney and internal obstruction of phlegm-turbidity, with symptoms such as sallow or yellowish complexion, soreness and weakness of the waist and knees, loss of appetite; fatigue, lower limb edema, a bland taste in the mouth and no desire to drink, frequent urination or nocturia, repeated occurrence of turbid urine; swollen and painful joints without redness, heaviness or numbness of the limbs, and difficulty in flexion and extension; dizziness and heaviness of the head, stuffiness and fullness in the chest and epigastrium, loss of appetite and nausea, dry mouth without the desire to drink, sticky feeling in the mouth, coughing up white sticky phlegm; pale and swollen tongue with tooth marks, thick and greasy white tongue coating, slippery or taut pulse; those with gouty nephropathy presenting the above syndromes.

[0045] The pharmaceutical preparation provided by the present invention has a simple prescription, a simple manufacturing process, small toxic and side effects, convenient administration, easy preparation of the medicament, and low cost. Detailed Embodiments

[0046] The technical solutions of the present invention will be further described below through specific embodiments. Those skilled in the art should understand that the specific embodiments are only for helping to understand the present invention and should not be regarded as specific limitations on the present invention.

[0047] Example 1

[0048] This example provides a traditional Chinese medicine composition for treating gouty nephropathy, including the following components in parts by weight:

[0049] 5 parts of Astragalus membranaceus, 9 parts of Codonopsis pilosula, 4 parts of Cinnamomum cassia, 12 parts of Eucommia ulmoides, 4 parts of Cornus officinalis, 12 parts of Cuscuta chinensis, 4 parts of Atractylodes macrocephala, 9 parts of Atractylodes lancea, 4 parts of Citrus reticulata Blanco, 9 parts of Poria cocos, 3 parts of Dioscorea septemloba Thunb. and 7.5 parts of Alisma orientale.

[0050] This example also provides a granule for treating gouty nephropathy, and its preparation method is as follows:

[0051] (1) Weigh the medicinal materials according to the ratio of the traditional Chinese medicine composition, add water with a mass 12 times that of the medicinal materials, soak for 1 hour, then decoct three times, each time for 1 hour. The water addition amounts for the second and third decoctions are both 9 times the mass of the medicinal materials. Filter the decoction liquid after each decoction, combine the filtrates, let it stand until room temperature, centrifuge, and take the supernatant to obtain the water extract;

[0052] (2) Under the conditions of a temperature of 65 °C and a vacuum degree of -0.07 MPa, concentrate the water extract under reduced pressure to obtain a clear paste with a relative density of 1.09 at 50 °C;

[0053] (3) Add ethanol to the clear paste until the ethanol content reaches 65 wt%, let it stand for 12 hours, take the supernatant, recover the ethanol until there is no alcohol smell, and then under the conditions of a temperature of 65 °C and a vacuum degree of -0.07 MPa, concentrate it under reduced pressure to obtain a thick paste with a relative density of 1.15 at 50 °C;

[0054] (4) Under the conditions of a temperature of 65 °C and a vacuum degree of -0.08 MPa, dry the thick paste under reduced pressure to obtain a dry extract (moisture ≤ 5%), pulverize it, and pass through an 80-mesh sieve to obtain dry extract powder;

[0055] (5) Mix the dry extract powder with sucralose, DL-malic acid, and an appropriate amount of dextrin evenly, prepare soft materials with an appropriate amount of 85% ethanol, granulate through a 14-mesh sieve, dry at 45 - 50 °C (moisture ≤ 5%), and size through a 12-mesh sieve to obtain the granule for treating gouty nephropathy.

[0056] Example 2

[0057] This example provides a traditional Chinese medicine composition for treating gouty nephropathy, which includes the following components in parts by weight:

[0058] Astragalus membranaceus 15 parts, Codonopsis pilosula 3 parts, Cinnamomum cassia 12 parts, Eucommia ulmoides 4 parts, Cornus officinalis 12 parts, Cuscuta chinensis 4 parts, Atractylodes macrocephala 12 parts, Atractylodes lancea 3 parts, Citrus reticulata Blanco 12 parts, Poria cocos 3 parts, Dioscorea septemloba Thunb. 9 parts, and Alisma orientale (Sam.) Juz. 2.5 parts.

[0059] This example also provides a granule for treating gouty nephropathy, and its preparation method is as follows:

[0060] (1) Weigh the medicinal materials according to the ratio of the traditional Chinese medicine composition, add water with a mass 7 times that of the medicinal materials, soak for 3 hours, then decoct three times, each time for 3 hours. The water addition amounts for the second and third decoctions are both 4 times the mass of the medicinal materials. Filter the decoction liquid after each decoction, combine the filtrates, let it stand until room temperature, centrifuge, and take the supernatant to obtain the water extract;

[0061] (2) Under the conditions of a temperature of 70 °C and a vacuum degree of -0.05 MPa, concentrate the water extract under reduced pressure to obtain a clear paste with a relative density of 1.12 at 50 °C;

[0062] (3) Add ethanol to the clear extract until the ethanol content reaches 75 wt%, let it stand for 24 hours, take the supernatant, recover ethanol until there is no alcohol smell, and then concentrate it under reduced pressure at a temperature of 70 °C and a vacuum degree of -0.05 MPa to a thick extract with a relative density of 1.20 at 50 °C;

[0063] (4) Dry the thick extract into a dry extract (moisture ≤ 5%) under reduced pressure at a temperature of 70 °C and a vacuum degree of -0.06 MPa, crush it, and pass through an 80-mesh sieve to obtain dry extract powder;

[0064] (5) Mix the dry extract powder with sucralose, DL-malic acid and an appropriate amount of dextrin, prepare soft materials with an appropriate amount of 85% ethanol, granulate through a 14-mesh sieve, dry at 45 - 50 °C (moisture ≤ 5%), and size through a 12-mesh sieve to obtain the granule for treating gouty nephropathy.

[0065] Example 3

[0066] This example provides a traditional Chinese medicine composition for treating gouty nephropathy, including the following components in parts by weight:

[0067] Astragalus membranaceus 8 parts, Codonopsis pilosula 7.5 parts, Cinnamon twig 6 parts, Eucommia ulmoides 10 parts, Cornus officinalis 6 parts, Cuscuta chinensis 10 parts, Atractylodes macrocephala 6 parts, Atractylodes lancea 7.5 parts, Tangerine peel 6 parts, Poria cocos 7.5 parts, Dioscorea septemloba 4.5 parts and Alisma orientale 6 parts.

[0068] This example also provides a granule for treating gouty nephropathy, and its preparation method is as follows:

[0069] (1) Weigh the medicinal materials according to the ratio of the traditional Chinese medicine composition, add 8 times the mass of the medicinal materials of water, soak for 2 hours, then decoct three times, each time for 1.5 hours. The water addition amounts for the second and third times are both 6 times the mass of the medicinal materials. Filter the decoction liquid after each decoction, combine the filtrates, let it stand until room temperature, centrifuge, and take the supernatant to obtain the water extract;

[0070] (2) Concentrate the water extract under reduced pressure at a temperature of 68 °C and a vacuum degree of -0.06 MPa to a clear extract with a relative density of 1.10 at 50 °C;

[0071] (3) Add ethanol to the clear extract until the ethanol content reaches 70 wt%, let it stand for 18 hours, take the supernatant, recover ethanol until there is no alcohol smell, and then concentrate it under reduced pressure at a temperature of 68 °C and a vacuum degree of -0.06 MPa to a thick extract with a relative density of 1.18 at 50 °C;

[0072] (4) Dry the thick extract into a dry extract (moisture ≤ 5%) under reduced pressure at a temperature of 68 °C and a vacuum degree of -0.07 MPa, crush it, and pass through an 80-mesh sieve to obtain dry extract powder;

[0073] (5) Mix the dry extract powder with sucralose, DL-malic acid and an appropriate amount of dextrin, prepare soft material with an appropriate amount of 85% ethanol, granulate through a 14-mesh sieve, dry at 45 - 50 °C (moisture ≤ 5%), and screen with a 12-mesh sieve to obtain the granule for treating gouty nephropathy.

[0074] Example 4

[0075] This example provides a traditional Chinese medicine composition for treating gouty nephropathy, including the following components in parts by weight:

[0076] 12 parts of Astragalus membranaceus, 4.5 parts of Codonopsis pilosula, 10 parts of Cinnamomum cassia, 6 parts of Eucommia ulmoides, 10 parts of Cornus officinalis, 6 parts of Cuscuta chinensis, 10 parts of Atractylodes macrocephala, 4.5 parts of Atractylodes lancea, 10 parts of Citrus reticulata Blanco, 4.5 parts of Poria cocos, 7.5 parts of Dioscorea septemloba and 4 parts of Alisma orientale.

[0077] This example also provides a granule for treating gouty nephropathy, and its preparation method is as follows:

[0078] (1) Weigh the medicinal materials according to the ratio of the traditional Chinese medicine composition, add 8 times the mass of water of the medicinal materials, soak for 2 hours, then decoct three times, each time for 1.5 hours. The water addition amount for the second and third times is 6 times the mass of the medicinal materials. Filter the decoction after each decoction, combine the filtrates, let it stand until room temperature, centrifuge, and take the supernatant to obtain the water extract.

[0079] (2) Concentrate the water extract under reduced pressure at a temperature of 68 °C and a vacuum degree of -0.06 MPa to obtain a clear extract with a relative density of 1.10 at 50 °C.

[0080] (3) Add ethanol to the clear extract until the ethanol content reaches 70 wt%, let it stand for 18 hours, take the supernatant, recover ethanol until there is no alcohol smell, and then concentrate it under reduced pressure at a temperature of 68 °C and a vacuum degree of -0.06 MPa to obtain a thick extract with a relative density of 1.18 at 50 °C.

[0081] (4) Dry the thick extract under reduced pressure at a temperature of 68 °C and a vacuum degree of -0.07 MPa to obtain a dry extract (moisture ≤ 5%), pulverize it, and sieve through an 80-mesh sieve to obtain the dry extract powder.

[0082] (5) Mix the dry extract powder with sucralose, DL-malic acid and an appropriate amount of dextrin, prepare soft material with an appropriate amount of 85% ethanol, granulate through a 14-mesh sieve, dry at 45 - 50 °C (moisture ≤ 5%), and screen with a 12-mesh sieve to obtain the granule for treating gouty nephropathy.

[0083] Example 5

[0084] This example provides a traditional Chinese medicine composition for treating gouty nephropathy, including the following components in parts by weight:

[0085] 10 parts of Astragalus membranaceus, 6 parts of Codonopsis pilosula, 8 parts of Cinnamomum cassia, 8 parts of Eucommia ulmoides, 8 parts of Cornus officinalis, 8 parts of Cuscuta chinensis, 8 parts of Atractylodes macrocephala, 6 parts of Atractylodes lancea, 8 parts of Citrus reticulata Blanco, 6 parts of Poria cocos, 6 parts of Dioscorea septemloba Thunb. and 5 parts of Alisma orientale (Sam.) Juz.

[0086] This example also provides a granule for treating gouty nephropathy, and its preparation method is as follows:

[0087] (1) Weigh the medicinal materials according to the ratio of the traditional Chinese medicine composition, add water 8 times the mass of the medicinal materials, soak for 2 hours, then decoct three times, each time for 1.5 hours. The water addition amount for the second and third times is 6 times the mass of the medicinal materials. After each decoction, filter the decoction liquid, combine the filtrates, let it stand until room temperature, centrifuge, and take the supernatant to obtain the water extract.

[0088] (2) Concentrate the water extract under reduced pressure at a temperature of 68°C and a vacuum degree of -0.06 MPa to obtain a clear paste with a relative density of 1.10 at 50°C.

[0089] (3) Add ethanol to the clear paste until the ethanol content reaches 70 wt%, let it stand for 18 hours, take the supernatant, recover the ethanol until there is no alcohol smell, and then concentrate it under reduced pressure at a temperature of 68°C and a vacuum degree of -0.06 MPa to obtain a thick paste with a relative density of 1.18 at 50°C.

[0090] (4) Dry the thick paste under reduced pressure at a temperature of 68°C and a vacuum degree of -0.07 MPa to obtain a dry extract (moisture ≤ 5%), crush it, and pass through an 80-mesh sieve to obtain the dry extract powder.

[0091] (5) Mix the dry extract powder with sucralose, DL-malic acid and an appropriate amount of dextrin, prepare a soft material with an appropriate amount of 85% ethanol, granulate through a 14-mesh sieve, dry at 45 - 50°C (moisture ≤ 5%), and screen with a 12-mesh sieve to obtain the granule for treating gouty nephropathy.

[0092] Efficacy test

[0093] Use the clear paste prepared in Example 5 for animal experiments to confirm its therapeutic effect on the uric acid nephropathy model induced by adenine and potassium oxonate fed with yeast.

[0094] 1. Experimental materials

[0095] 1.1. Experimental animals

[0096] 60 healthy clean-grade male SD rats (provided by Beijing Vital River Laboratory Animal Technology Co., Ltd., animal production license number: SCXK (Beijing) 2021-0006), 8 weeks old, body weight 250 ± 20, fed with standard pellet feed and given free access to water. The ventilation conditions are provided by an automatic ventilation system, the ventilation frequency is 8 - 15 times / h, the lighting is 12 h / day, the temperature is 22 - 26°C, and the humidity is 50 - 60%.

[0097] 1.2. Main reagents

[0098] Reagent kits for the determination of uric acid, creatinine, and urea; potassium oxonate (prepared into an injection with a concentration of 25 mg / mL using sterile injection water); adenine (prepared into a suspension with a concentration of 4 mg / mL using sterile injection water); allopurinol (prepared into a suspension with a concentration of 0.525 mg / mL using sterile injection water).

[0099] 2. Experimental methods

[0100] 2.1. Grouping and model establishment

[0101] After 1 week of adaptive feeding of rats, they were divided into a normal control group, a model control group, high, medium, and low dose groups of the gouty nephropathy formula, and an allopurinol group according to the random number table method, with 10 rats in each group. The normal control group was given ordinary feed and intragastric administration of 25 mL / kg distilled water and abdominal subcutaneous injection of 4 mL / kg sterile injection water every day. The remaining 5 groups were fed with 10% yeast powder feed and given intragastric administration of 0.1 g / kg adenine and abdominal subcutaneous injection of 0.1 g / kg potassium oxonate every day for continuous model establishment for 2 weeks.

[0102] On the 14th day of the experiment, after fasting for 8 h, 2 rats were randomly selected from the model control group, sacrificed, and kidney tissues were taken for HE staining. Observation of the kidney tissue pathology showed that urate crystals were deposited in the renal tubules and renal interstitium, indicating that the rat model of uric acid nephropathy was successfully established.

[0103] After model establishment, each group of rats was given intragastric administration of drugs simultaneously every day. Among them, the high, medium, and low dose groups of the gouty nephropathy formula were all given the extract prepared in Example 5 by intragastric administration. The administration doses (calculated based on the mass of the traditional Chinese medicine composition) of the high, medium, and low dose groups of the gouty nephropathy formula were 15.66 g / kg, 7.83 g / kg, and 3.91 g / kg respectively; the allopurinol group was given allopurinol 9 mg / kg by intragastric administration (equivalent to 100 mg / day for an adult with a body weight of 70 kg); the normal control group and the model control group were given 20 mL / kg distilled water by intragastric administration; continuous administration was carried out for 2 weeks.

[0104] On the day after the last administration, the rats were weighed and anesthetized by intraperitoneal injection of glutaraldehyde. Blood was collected from the abdominal aorta of the rats and centrifuged at a centrifugal radius of 8 cm and a rotational speed of 10,000 r / min for 5 min using a low-temperature high-speed centrifuge (Heraeus, Biofuge Stratos, Germany) to obtain serum. The serum uric acid, creatinine, and urea contents of each group of rats were measured using a fully automatic biochemical analyzer (Olympus, AU2700, Japan) according to the kit instructions by the sarcosine oxidase method, urease method, and uricase method respectively.

[0105] 3. Statistical methods

[0106] The measurement data were expressed as mean ± standard deviation , and one-way analysis of variance was used for comparison among multiple groups. P<0.05 was considered statistically significant, and P<0.01 indicated extremely significant statistical significance.

[0107] 4. Experimental results

[0108] The data of serum uric acid, creatinine, and urea content in each group of rats are shown in Table 1.

[0109] Table 1 Content of creatinine, urea, and uric acid in rat serum (μmol / L, )

[0110]

[0111]

[0112] Note: Compared with the normal control group, a P<0.01; compared with the model control group, b P<0.05, bb P<0.01; compared with the allopurinol group, c P<0.05, cc P<0.01.

[0113] Creatinine is an important indicator for evaluating renal function. When the creatinine level in the blood increases, it indicates that the filtration function of the kidney is impaired; urea is the end product of protein metabolism, and urea is mainly filtered through the kidney and excreted into the urine, so urea can be used to evaluate renal function.

[0114] As can be seen from Table 1, compared with the normal control group, the levels of uric acid, creatinine, and urea in the model control group of rats were significantly increased (P<0.01).

[0115] Compared with the model control group, the levels of uric acid and creatinine in the allopurinol group and each dose group of the gouty nephropathy formula were significantly decreased (P<0.01); the serum urea levels in the high and medium dose groups of the gouty nephropathy formula were significantly decreased (P<0.01); while allopurinol and the low dose of the gouty nephropathy formula could not significantly decrease the urea level (P>0.05).

[0116] There was no significant difference in the effect of reducing uric acid level between the high dose of the gouty nephropathy formula and allopurinol (P>0.05); the effects of the medium and low doses of the gouty nephropathy formula in reducing uric acid level were lower than those of allopurinol, and there was a significant difference compared with the allopurinol group.

[0117] Allopurinol did not show the effect of reducing urea level (no significant difference compared with the model control group), but had the effect of reducing creatinine level (significant difference compared with the model control group). The high- and medium-dose Tongfengxing Shenbing Decoction could significantly reduce creatinine and urea levels, showing a very significant difference compared with the model group (P<0.01), and a significant difference compared with the allopurinol group (P<0.05 for creatinine level and P<0.01 for urea level).

[0118] The above experimental results indicate that the Tongfengxing Shenbing Decoction provided by the present invention can significantly reduce the uric acid, creatinine, and urea levels in rats with uric acid nephropathy at high and medium doses (P<0.05 or P<0.01), confirming that it can improve renal function and has a good therapeutic effect on gouty nephropathy.

[0119] The above are only specific embodiments of the present disclosure, enabling those skilled in the art to understand or implement the present disclosure. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present disclosure. Therefore, the present disclosure will not be limited to these embodiments described herein, but will conform to the broadest scope consistent with the principles and novel features disclosed herein.

Claims

1. A traditional Chinese medicine composition for treating gouty nephropathy, characterized in that, It comprises the following components: Astragalus membranaceus, Codonopsis pilosula, Cinnamomum cassia, Eucommia ulmoides, Cornus officinalis, Cuscuta chinensis, Atractylodes macrocephala, Atractylodes lancea, Citrus reticulata, Poria cocos, Dioscorea septemloba, and Alisma orientale.

2. The traditional Chinese medicine composition according to claim 1, wherein The traditional Chinese medicine composition comprises the following components in parts by weight: 5 - 15 parts of Astragalus membranaceus, 3 - 9 parts of Codonopsis pilosula, 4 - 12 parts of Cinnamomum cassia, 4 - 12 parts of Eucommia ulmoides, 4 - 12 parts of Cornus officinalis, 4 - 12 parts of Cuscuta chinensis, 4 - 12 parts of Atractylodes macrocephala, 3 - 9 parts of Atractylodes lancea, 4 - 12 parts of Citrus reticulata, 3 - 9 parts of Poria cocos, 3 - 9 parts of Dioscorea septemloba, and 2.5 - 7.5 parts of Alisma orientale.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: 8 - 12 parts of Astragalus membranaceus, 4.5 - 7.5 parts of Codonopsis pilosula, 6 - 10 parts of Cinnamomum cassia, 6 - 10 parts of Eucommia ulmoides, 6 - 10 parts of Cornus officinalis, 6 - 10 parts of Cuscuta chinensis, 6 - 10 parts of Atractylodes macrocephala, 4.5 - 7.5 parts of Atractylodes lancea, 6 - 10 parts of Citrus reticulata, 4.5 - 7.5 parts of Poria cocos, 4.5 - 7.5 parts of Dioscorea septemloba, and 4 - 6 parts of Alisma orientale.

4. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that The traditional Chinese medicine composition comprises the following components in parts by weight: 10 parts of Astragalus membranaceus, 6 parts of Codonopsis pilosula, 8 parts of Cinnamomum cassia, 8 parts of Eucommia ulmoides, 8 parts of Cornus officinalis, 8 parts of Cuscuta chinensis, 8 parts of Atractylodes macrocephala, 6 parts of Atractylodes lancea, 8 parts of Citrus reticulata, 6 parts of Poria cocos, 6 parts of Dioscorea septemloba, and 5 parts of Alisma orientale.

5. A pharmaceutical preparation for treating gouty nephropathy, characterized in that, The pharmaceutical preparation contains the active ingredients of the traditional Chinese medicine composition according to any one of claims 1 - 4.

6. The pharmaceutical preparation according to claim 5, characterized in that, The pharmaceutical preparation further comprises an excipient.

7. The pharmaceutical preparation according to claim 6, characterized in that, The excipient includes one or more of sucralose, DL - malic acid, and dextrin.

8. The pharmaceutical preparation according to any one of claims 5-7, characterized in that, The dosage form of the pharmaceutical preparation is tablet, capsule, granule, or oral liquid.

9. A method for preparing a pharmaceutical preparation according to any one of claims 5-8, characterized in that, The preparation method comprises the following steps: (1) Perform water extraction on the traditional Chinese medicine composition according to any one of claims 1 - 4 to obtain a water extract; (2) Prepare the water extract into the dosage form of the pharmaceutical preparation.

10. The preparation method according to claim 9, characterized in that, The water extraction step in step (1) includes: soaking the traditional Chinese medicine composition in water for 1 - 3 h, then decocting at least 3 times, each time for 1 - 3 h, filtering the decoction, and combining the filtrates to obtain the water extract; Preferably, in the water extraction in step (1), the total mass of water is 15 - 30 times the mass of the traditional Chinese medicine composition; Preferably, the step of preparing the water extract into the dosage form of the pharmaceutical preparation includes: concentrating the water extract into a clear paste with a relative density of 1.09 - 1.12 at 50 °C; adding ethanol to make the ethanol content 65 - 75 wt%, standing for 12 - 24 h, taking the supernatant and recovering ethanol, then concentrating into a thick paste with a relative density of 1.15 - 1.20 at 50 °C; drying into a dry extract, pulverizing to obtain dry extract powder; mixing the dry extract powder with sucralose, DL - malic acid, and dextrin to make granules; Preferably, the concentration method is: under the conditions of a temperature of 65 - 70 °C and a vacuum degree of - 0.05 to - 0.07 MPa, perform vacuum concentration; Preferably, the drying method is: under the conditions of a temperature of 65 - 70 °C and a vacuum degree of - 0.06 to - 0.08 MPa, perform vacuum drying.

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