A Chinese medicine composition for treating chronic renal failure and its preparation method and application

Abstract

The invention discloses a Chinese medicine composition for treating chronic renal failure, a preparation method and application thereof, and belongs to the technical field of Chinese medicine preparation. The composition is made of the following raw materials in parts by weight: 2-4 parts of Astragalus, 3-4 parts of Rhubarb Carbon, 3-4 parts of Raw Rhubarb, 1-3 parts of Chuanxiong, 1-3 parts of Psoralea corylifolia, 12-15 parts of Taraxacum, 12-15 parts of Stir-fried Cassia Seed, 1-3 parts of Citrus aurantium, and 5-7 parts of Scutellaria barbata. The invention has a scientific prescription and precise proportions, and has the effects of invigorating the kidney and activating blood circulation, lowering turbidity and detoxifying, and calming the five internal organs. It is an effective prescription for treating chronic renal failure, and is used for patients with kidney deficiency, blood stasis, and turbid toxin disturbance syndrome of chronic renal failure caused by various reasons. The Chinese medicine composition provided by the invention has a definite overall therapeutic effect, significantly reduces the serum Scr level, and has significant differences in ACR, eGFR, BUN, and Hb before and after treatment. It can significantly improve the renal function indicators of patients with chronic renal failure, delay the development of chronic kidney disease, and effectively improve the quality of life of patients.

Description

Technical Field

[0001] The invention relates to a traditional Chinese medicine composition for treating chronic renal failure and a preparation method and application thereof, belonging to the technical field of traditional Chinese medicine preparation. Background Art

[0002] Clinically, chronic kidney disease (CKD) is divided into 5 stages, of which stages 3-5 are chronic renal failure (CRF). Chronic renal failure is a common manifestation of various chronic kidney diseases in the late stage. It is a chronic progressive renal parenchymal damage that eventually leads to uremia. Symptoms of chronic renal failure include increased blood creatinine, electrolyte imbalance, metabolic acidosis, renal anemia, nausea and vomiting, increased nocturia, clear and long urination, itching all over the body, chills and cold limbs, etc. Traditional Chinese medicine believes that chronic renal failure is caused by endogenous turbid toxins due to kidney deficiency, which cannot be excreted from the body, resulting in disorders that affect the functions of the five internal organs, meridians, and limbs of the human body. At present, some traditional Chinese medicine theories use kidney-tonifying, blood-activating, turbid-reducing and toxin-removing methods to treat chronic renal failure.

[0003] In traditional Chinese medicine, it is common to treat chronic renal failure with raw rhubarb as the main ingredient to clear the bowels and expel turbidity. For example, Urea Clearing Granules are made of rhubarb, astragalus, mulberry bark, codonopsis, atractylodes, poria, processed polygonum multiflorum, white peony root, salvia miltiorrhiza, and plantain. The raw rhubarb in the recipe clears the bowels and expel turbidity, allowing dampness and turbidity to be expelled from the stool. Chronic renal failure patients have turbidity and toxicity, but their kidney yang gradually declines, so detoxification should not use too many cold and cool products to prevent damage to yang. However, raw rhubarb is a cold product, and excessive use will have too strong a laxative effect, which can easily cause severe diarrhea, damage the vital energy, and worsen the condition; too little raw rhubarb will not have a significant therapeutic effect.

[0004] It should be noted that the above contents belong to the technical knowledge of the inventor and do not necessarily constitute prior art. Summary of the invention

[0005] In order to solve the problems existing in the prior art, the present invention provides a Chinese medicine composition for treating chronic renal failure, a preparation method thereof and an application thereof. The prescription of the provided Chinese medicine composition is derived from more than 50 years of clinical practice of Zhang Daning, a national medical master, and follows the traditional Chinese medicine theory. The prescription is scientific and the ratio is precise. It has the effects of tonifying the kidney and activating blood circulation, lowering turbidity and detoxifying, eliminating the old and bringing in the new, and calming and harmonizing the five internal organs. It is an effective prescription for treating chronic renal failure.

[0006] The present invention achieves the above-mentioned purpose by adopting the following technical solutions:

[0007] On the one hand, the present invention provides a Chinese medicine composition for treating chronic renal failure, which is made of the following raw materials in parts by weight: 2-4 parts of astragalus, 3-4 parts of rhubarb charcoal, 3-4 parts of raw rhubarb, 1-3 parts of chuanxiong, 1-3 parts of psoralea corylifolia, 12-15 parts of dandelion, 12-15 parts of stir-fried cassia seed, 1-3 parts of fructus aurantii, and 5-7 parts of Scutellaria barbata. In a preferred embodiment, the weight parts of each raw material in the Chinese medicine composition are: 3 parts of astragalus, 3.5 parts of rhubarb charcoal, 3.5 parts of raw rhubarb, 2 parts of chuanxiong, 2 parts of psoralea corylifolia, 15 parts of dandelion, 15 parts of stir-fried cassia seed, 2 parts of fructus aurantii, and 6 parts of Scutellaria barbata.

[0008] Furthermore, the extract of the traditional Chinese medicine composition provided by the present invention is added to a pharmaceutically acceptable carrier to prepare an oral preparation, which includes but is not limited to an oral liquid, granules, tablets, capsules or pills.

[0009] Furthermore, the extract of the Chinese medicine composition is a water-extracted dry paste, the internal preparation is a granule, and the carrier includes auxiliary materials in the following weight percentages of the water-extracted dry paste: 0.02% to 0.03% sucralose, 4% to 6% sorbitol, 9% to 11% maltodextrin, and 1.8% to 2.0% microcrystalline cellulose.

[0010] In one specific embodiment, the preparation method of the Chinese medicine composition granules provided by the present invention comprises the following steps: adding sucralose, sorbitol, and maltodextrin to the water extract paste and mixing evenly, spray drying, adding microcrystalline cellulose and mixing evenly, and dry granulating to obtain the granules of the Chinese medicine composition.

[0011] The preparation method of the water-extracted clear paste comprises the following steps:

[0012] Mix the remaining raw materials except the raw rhubarb, add 8 to 12 times the weight of water, boil for 1 to 2 hours, and filter to obtain a residue and a filtrate; add the raw rhubarb to the residue, add 8 to 10 times the weight of water, boil for 0.5 to 1.5 hours, and filter to obtain a residue and a filtrate;

[0013] The two filtrates were combined and concentrated under reduced pressure at 50-60°C to a water-extracted clear paste having a relative density of 1.03-1.10 measured at 50°C.

[0014] On the other hand, the present invention also provides the use of the traditional Chinese medicine composition in preparing a medicine for chronic renal failure.

[0015] The beneficial effects of this application include but are not limited to:

[0016] Chronic renal failure is due to the endogenous turbid toxins caused by kidney deficiency, so in the Chinese medicine composition for the treatment of chronic renal failure provided by the present invention, Astragalus is used to invigorate qi and raise yang, and Chuanxiong is used to promote blood circulation and promote qi, and the two are used together to invigorate the kidney and promote blood circulation. Raw rhubarb is used to reduce turbidity and detoxify, and raw rhubarb can promote blood circulation and remove blood stasis, eliminate lumps and accumulations, digest food and remove stagnation, and cleanse the stomach and intestines, which is a good medicine for the treatment of chronic renal failure. Dandelion is a heat-clearing and detoxifying medicine, which has the effects of clearing heat and detoxifying, reducing swelling and dispersing knots, and diuresis and relieving stranguria. It can purge the evil fire and heat toxins caused by various turbid toxins in the body, and dandelion is used to eliminate dampness, detoxify and remove dampness without hurting the body. Chronic renal failure patients are due to turbid toxins in the body, and stasis generates fire again, so dandelion is used to clear heat, purge fire and detoxify, and the dosage is large. By combining dandelion with raw rhubarb, not only the raw rhubarb dosage is reduced, but the two medicines are also used together to enhance their respective drug effects, and there is a synergistic effect.

[0017] Furthermore, Psoralea corylifolia nourishes the kidney and strengthens the spleen, consolidates the essence and stops nocturnal emission, and can be used as an adjuvant to Astragalus membranaceus; Rhubarb charcoal is made by stir-frying rhubarb charcoal, which can cool blood, resolve blood stasis and stop bleeding; Stir-fried Cassia seed nourishes yin, relieves heat, soothes the liver and nourishes the kidney, and can be used as an adjuvant to Rhubarb; Scutellaria barbata clears away heat and detoxifies, resolves blood stasis and promotes diuresis, and can be used as an adjuvant to Taraxacum mongolicum to detoxify and remove dampness; Citrus aurantium breaks up Qi, promotes Qi circulation and eliminates abdominal distension, and breaks up masses, and can both assist in promoting blood circulation to promote Qi circulation and reduce Qi to reduce turbid toxins.

[0018] The preparation method of the Chinese medicine composition for treating chronic renal failure provided by the present invention reasonably selects auxiliary materials to correct the flavor of the extract and reduce the hygroscopicity of the extract, thereby improving the stability of the properties of the granule preparation, solving the problems that the extract has a strong bitter taste, the extract is easy to absorb moisture and stick after drying due to the presence of polysaccharides, the yield of the drug preparation is low, and it is difficult to granulate.

[0019] In summary, the nine herbs in the prescription of the present invention are combined, the prescription is scientific, the ratio is accurate, and it has the effects of tonifying the kidney and activating blood circulation, reducing turbidity and detoxifying, removing the old and bringing in the new, and calming the five internal organs. It is an effective prescription for treating chronic renal failure and is used for patients with chronic renal failure caused by various reasons, such as kidney deficiency and blood stasis, and turbid toxin disturbance syndrome. Clinical data show that the Chinese medicine composition provided by the present invention has a definite overall therapeutic effect, the serum Scr level is significantly reduced, and there are significant differences in ACR, eGFR, BUN, and Hb before and after treatment. It also has a certain effect of increasing Hb, and can significantly improve the renal function indicators of patients with chronic renal failure, and delay the development of chronic kidney disease, effectively improving the quality of life of patients. DETAILED DESCRIPTION

[0020] The present invention will be further described in detail through specific embodiments in the following content. However, it should be pointed out that the following specific embodiments only provide specific operation examples of the present invention in an exemplary manner, but the protection scope of the present invention is not limited thereto. The protection scope of the present invention is limited only by the claims. It is obvious to those skilled in the art that various other improvements and replacements can be made to the embodiments described in the present invention within the protection scope defined by the claims of the present invention, and the same technical effects can still be achieved, thereby achieving the ultimate technical purpose of the present invention.

[0021] Unless otherwise specified, all raw materials in this specification were purchased from commercial sources.

[0022] Description of the medicinal materials used in this invention application:

[0023] Astragalus: The dried root of the leguminous plants Astragalus mongolica or Astragalus membranaceus.

[0024] Rhubarb charcoal: a processed product of the Chinese medicinal herb rhubarb, made by frying rhubarb slices in a pan over high heat until the surface is charred black and the inside is charred brown, then spraying a little water on it and taking it out to dry.

[0025] Raw rhubarb: the dried roots and rhizomes of Rheum palmatum, Rheum tanguticum or Rheum officinale of the Polygonaceae family.

[0026] Chuanxiong: The dried rhizome of the Umbelliferae plant Chuanxiong.

[0027] Psoralea corylifolia: The dried mature fruit of the leguminous plant Psoralea corylifolia.

[0028] Dandelion: The dried whole herb of dandelion, alkali dandelion or several plants of the same genus in the Asteraceae family.

[0029] Fried Cassia Seeds: The dried mature seeds of the leguminous plant Cassia tora or Cassia tora (Cassia sibiricum), which are fried in the stir-fry method until they are slightly swollen and fragrant.

[0030] Citrus aurantium: the dried unripe fruit of the Rutaceae plant sour orange and its cultivated varieties.

[0031] Scutellaria barbata: the dried whole herb of Scutellaria barbata, a plant of the Lamiaceae family.

[0032] Embodiment 1:

[0033] The Chinese medicine composition for treating chronic renal failure provided in this embodiment is prepared from the following raw materials:

[0034] 300g of Astragalus, 350g of Rhubarb Charcoal, 350g of Raw Rhubarb, 200g of Chuanxiong, 200g of Psoralea corylifolia, 1500g of Taraxacum mongolicum, 1500g of Stir-fried Cassia Seed, 200g of Citrus aurantium, and 600g of Scutellaria barbata.

[0035] The preparation method of the Chinese medicine composition for treating chronic renal failure provided in this embodiment is as follows:

[0036] (1) mixing the remaining raw materials except the raw rhubarb, adding 10 times the weight of water, boiling for 2 hours, and filtering to obtain a residue and a filtrate; adding the raw rhubarb to the residue, adding 9 times the weight of water, boiling for 1.5 hours, and filtering to obtain a residue and a filtrate;

[0037] (2) combining the two filtrates, and concentrating under reduced pressure at 50-60° C. to obtain a water-extracted clear paste having a relative density of 1.03-1.10 at 50° C.;

[0038] (3) Add sucralose, sorbitol, and maltodextrin to the water extract, mix evenly, spray dry, add microcrystalline cellulose, mix evenly, and dry granulate to obtain the granules of the traditional Chinese medicine composition.

[0039] The weight percentages of sucralose, sorbitol, maltodextrin and microcrystalline cellulose in the water-extracted dry paste (the dry matter of the clear paste) are as follows: sucralose accounts for 0.02%, sorbitol accounts for 5%, maltodextrin accounts for 10%, and microcrystalline cellulose accounts for 2%.

[0040] Embodiment 2:

[0041] The Chinese medicine composition for treating chronic renal failure provided in this embodiment is prepared from the following raw materials:

[0042] 200g of Astragalus, 300g of Rhubarb Charcoal, 300g of Raw Rhubarb, 100g of Chuanxiong, 100g of Psoralea corylifolia, 1300g of Taraxacum mongolicum, 1300g of Stir-fried Cassia Seed, 200g of Citrus aurantium, and 500g of Scutellaria barbata.

[0043] The preparation method of the Chinese medicine composition for treating chronic renal failure provided in this embodiment is as follows:

[0044] (1) mixing the remaining raw materials except the raw rhubarb, adding 12 times the weight of water, boiling for 1.5 hours, and filtering to obtain a residue and a filtrate; adding the raw rhubarb to the residue, adding 10 times the weight of water, boiling for 1 hour, and filtering to obtain a residue and a filtrate;

[0045] (2) combining the two filtrates, and concentrating under reduced pressure at 50-60° C. to obtain a water-extracted clear paste having a relative density of 1.03-1.10 at 50° C.;

[0046] (3) adding sucralose, sorbitol, and maltodextrin to the water extract, mixing evenly, spray drying, adding microcrystalline cellulose, mixing evenly, and dry granulating to obtain granules of the traditional Chinese medicine composition;

[0047] The weight percentages of sucralose, sorbitol, maltodextrin and microcrystalline cellulose in the water-extracted dry paste are as follows: sucralose accounts for 0.02%, sorbitol accounts for 5%, maltodextrin accounts for 10%, and microcrystalline cellulose accounts for 2%.

[0048] Embodiment 3:

[0049] The Chinese medicine composition for treating chronic renal failure provided in this embodiment is prepared from the following raw materials:

[0050] 400g of Astragalus, 400g of Rhubarb Charcoal, 400g of Raw Rhubarb, 300g of Chuanxiong, 300g of Psoralea corylifolia, 1200g of Taraxacum, 1200g of Stir-fried Cassia Seed, 200g of Citrus aurantium, and 700g of Scutellaria barbata.

[0051] The preparation method of the Chinese medicine composition for treating chronic renal failure provided in this embodiment is the same as that in Example 1.

[0052] In order to verify the therapeutic effect of the Chinese medicine composition for treating chronic renal failure provided by the invention, the inventors of the present application conducted the following experiments.

[0053] 1. Research on the composition and proportion of Chinese medicine composition:

[0054] 1.1 Composition of the test drug samples

[0055] Sample 1: 300g Astragalus, 350g Rhubarb charcoal, 700g Raw Rhubarb, 200g Chuanxiong, 200g Psoralea corylifolia, 350g Taraxacum mongolicum, 1500g Stir-fried Cassia Seed, 200g Citrus aurantium, 600g Scutellaria barbata.

[0056] Sample 2: 300g Astragalus, 700g Rhubarb charcoal, 350g Raw Rhubarb, 200g Chuanxiong, 200g Psoralea corylifolia, 350g Taraxacum mongolicum, 1500g Stir-fried Cassia Seed, 200g Citrus aurantium, and 600g Scutellaria barbata.

[0057] Sample 3: 300g of Astragalus, 350g of Rhubarb Charcoal, 350g of Raw Rhubarb, 200g of Chuanxiong, 200g of Psoralea corylifolia, 1500g of Taraxacum mongolicum, 1500g of Stir-fried Cassia Seed, 200g of Citrus aurantium, and 600g of Scutellaria barbata; Sample 3 has the same prescription as Example 1 of the present invention.

[0058] Sample 4: 300g Astragalus, 350g Rhubarb charcoal, 350g Cooked Rhubarb, 200g Chuanxiong, 200g Psoralea corylifolia, 1500g Taraxacum mongolicum, 1500g Stir-fried Cassia seed, 200g Citrus aurantium, 600g Scutellaria barbata.

[0059] Sample 5: 300g Astragalus, 350g Rhubarb charcoal, 350g Raw Rhubarb, 200g Chuanxiong, 200g Psoralea corylifolia, 1500g stir-fried Cassia seed, 200g Citrus aurantium, 2100g Scutellaria barbata.

[0060] 1.2 Preparation of test drug samples

[0061] The preparation method of each test drug sample is the same, and the steps are as follows:

[0062] Weigh each medicinal material according to the prescription ratio of the test drug samples 1-5, add 10 times the weight of water to the remaining medicinal materials except rhubarb (raw rhubarb or cooked rhubarb in the prescription), heat to boiling, and continue to decoct for 2 hours, filter to obtain filtrate and filter residue; add rhubarb to the filter residue, add 9 times the weight of water, decoct for 1.5 hours, and filter. Combine the two filtrates, decompress and concentrate at 50-60°C to form a standard decoction, the concentration of each 1ml of the standard decoction is equivalent to 1g of the raw medicinal material, and store it at -20°C after packaging for standby use.

[0063] 1.3 Animal Experiment Methods:

[0064] 1.3.1 Experimental animals

[0065] Test animals: 80 SPF male SD rats, weight: 150±10, purchased from the Institute of Biology, Shandong Academy of Sciences, license number SCXK(Lu)20220006.

[0066] Modeling drug: adenine (Aladdin, batch number A108805).

[0067] 1.3.2 Preparation of chronic renal failure rat model

[0068] After 7 days of adaptive feeding, 80 SD rats were randomly selected as blank control group. The remaining 70 rats were gavaged with adenine solution to prepare CRF rat model. The drug was gavaged according to body weight. 2.5g adenine was added to 100ml normal saline to make a suspension with a concentration of 2.5%. The concentration was 200mg·kg -1 ·d -1 The mice were given the drug by intragastric administration once a day, and the blank group was given the same dose of normal saline. The modeling period was 28 days.

[0069] 1.3.3 Grouping and Dosing

[0070] The rats with successful modeling were divided into model group and sample 1 group (administered dose 4.23 ml·kg －1 ·d) and sample 2 (dosage 4.23 ml·kg －1 ·d), sample 3 (dosage 5.22ml·kg －1 ·d), sample 4 (dosage 5.22ml·kg －1 ·d,) and sample 5 (dosage 5.22ml·kg －1·d), 10 mice in each group were given drugs by gavage once a day according to the dosage, and the blank group and model group were given 1 ml of drinking water by gavage for 4 consecutive weeks.

[0071] After continuous intragastric administration for 1 week, the diarrhea of ​​rats in each group was observed every other week, and the diarrhea index of each group was calculated according to the diarrhea rating standard in "Pharmacological Experimental Methodology" (3rd edition). The calculation formula is: diarrhea index = loose stool rate × loose stool grade. The loose stool rate is the ratio of the number of loose stools discharged by each animal to the total number of stools; the loose stool grade indicates the degree of loose stools, and is divided into 4 levels according to the size of the stain area formed by the loose stool contaminating the filter paper, that is, the contamination diameter ≤1cm is level 1; 1-1.9cm is level 2; 2-3cm is level 3; >3cm is level 4.

[0072] 1.3.4 Sample collection

[0073] After the treatment, 20% urethane (5 ml / kg) was injected intraperitoneally for anesthesia, the abdominal cavity was opened along the midline of the abdomen, 5 ml of blood was collected from the abdominal aorta, and the serum was separated by centrifugation and diluted with a certain proportion of normal saline. The serum Scr and BUN levels were detected by automatic biochemical analyzer.

[0074] 1.3.5 Experimental results

[0075] Table 1 Diarrhea index of rats in each group

[0076]

[0077]

[0078] Note: Compared with the model group, # P<0.01, * P<0.05

[0079] The rat diarrhea index observation experiment in Table 1 shows that the rats in the model group and the treatment group have different degrees of diarrhea. Compared with the model group, the diarrhea of ​​the rats in the sample 1 treatment group is the most serious, because the dosage of raw rhubarb in the prescription is too large; the diarrhea of ​​the rats in the sample 2, sample 3 (the sample of the present invention) and sample 5 treatment groups is similar; compared with the sample 1 treatment group, the purgative effect of the sample 3 (the sample of the present invention) treatment group is weakened after the raw rhubarb is reduced; the defecation of the sample 4 treatment group is similar to that of the model group, and the purgative condition is not aggravated after the raw rhubarb is replaced by cooked rhubarb.

[0080] Table 2 Changes in body weight of rats in each group before and after treatment

[0081] Group Before treatment (g) After treatment (g) Blank Group 365.8±23.7 455.9±32.2 Model Group <![CDATA[258.6±20.3 # ]]> <![CDATA[286.5±17.3 # ]]> Sample 1 group <![CDATA[261.4±17.4 # ]]> <![CDATA[304.6±21.6 # ]]> Sample 2 group <![CDATA[265.3±24.1 # ]]> <![CDATA[311.5±23.8 #* ]]> Sample 3 (samples of the present invention) <![CDATA[259.1±15.9 # ]]> <![CDATA[332.9±16.3 #@ ]]> Sample 4 groups <![CDATA[267.3±18.1 # ]]> <![CDATA[303.8±19.7 # ]]> Sample 5 groups <![CDATA[257.2±16.6 # ]]> <![CDATA[301.4±17.1 #* ]]>

[0082] Note: Compared with the blank group, # P<0.01; compared with the model group, @P<0.01, * P<0.05.

[0083] The changes in body weight in Table 2 show that, compared with the blank group, the body weight of rats in each group increased slowly (P<0.01). Compared with the model group, the body weight of rats in the sample 3 (the sample of the present invention) treatment group increased significantly after treatment (P<0.01).

[0084] Table 3 Comparison of serum biochemical indexes of rats in each group after treatment

[0085] Group Scr (μmol / L) BUN (mmol / L) Blank Group 47.96±5.34 5.77±0.43 Model Group <![CDATA[186.7±22.2 # ]]> <![CDATA[22.33±2.19 # ]]> Sample 1 group <![CDATA[151.2±17.3 #@ ]]> <![CDATA[16.33±4.12 #@ ]]> Sample 2 group <![CDATA[169.4±19.1 # ]]> <![CDATA[18.12±3.11 #* ]]> Sample 3 (samples of the present invention) <![CDATA[141.7±16.6 #@ ]]> <![CDATA[14.01±3.28 #@ ]]> Sample 4 groups <![CDATA[174.3±18.5 # ]]> <![CDATA[19.46±4.37 # ]]> Sample 5 groups <![CDATA[158.9±16.2 #* ]]> <![CDATA[17.18±4.91 #* ]]>

[0086] Note: Compared with the blank group, # P<0.01; compared with the model group, * P<0.05, @ P<0.01.

[0087] The serum biochemical indices in Table 3 showed that, compared with the model group, sample group 1 and sample group 3 (samples of the present invention) had a significant improvement effect on the serum Scr and BUN levels of the model rats (P < 0.01).

[0088] Furthermore, it can be seen from Tables 1 and 3 that, compared with Sample Group 1, Sample Group 2 reduced the amount of raw rhubarb and increased the amount of rhubarb charcoal, and the serum Scr and BUN clearance effects were weakened; Sample 3 (the sample of the present invention) increased the amount of dandelion and reduced the amount of raw rhubarb, which can significantly improve the drug's turbidity-reducing and detoxifying effects while reducing the purgative effect, playing a synergistic role; Compared with Sample Group 3, after the raw rhubarb was replaced with cooked rhubarb in Sample Group 4, the improvement effect of serum Scr and BUN levels in the modeling rats was worse than that in Sample 3 (the sample of the present invention); After the amount of Scutellaria barbata was increased while dandelion was removed from Sample Group 5, the improvement effect of serum Scr and BUN levels in the modeling rats was worse than that in Sample 3 (the sample of the present invention), indicating that there is a correlation between dandelion and other ingredients in the prescription of the present invention, which affects the overall efficacy of the prescription.

[0089] The above experimental studies show that the rats in the chronic renal failure model group and the treatment group had significantly reduced defecation and urination compared with the blank group, and their weight gain was slow. In the treatment group, the raw rhubarb dosage in sample group 1 was larger, and the purgative effect was the strongest. The rats gained weight slowly, had less urine, and had a poor mental state. Sample group 2 reduced the dosage of raw rhubarb and increased the dosage of rhubarb charcoal. Sample group 4 removed raw rhubarb and used cooked rhubarb instead. Although the purgative effect did not increase, the renal function Scr and BUN indicators were not ideal. In the prescription, dandelion and barbata are both heat-clearing and detoxifying drugs. Sample group 5 only used barbata to clear heat and detoxify, and increased its dosage at the same time. The improvement effect on renal function indicators was not as good as the combination of dandelion and barbata. This shows that the dandelion not only plays a role in clearing heat and detoxifying, but is also indispensable in the overall efficacy of the prescription. Sample group 3 (samples of the present invention) reduced the amount of raw rhubarb and increased the amount of dandelion. After treatment, the purgative effect was milder, and the rats' diet, weight gain rate and mental state were relatively good, and the renal function indexes were significantly improved. The experiment showed that dandelion played a role of reducing the amount and increasing the effect after being compatible with raw rhubarb. Therefore, sample group 3 (samples of the present invention) is the best compatibility combination.

[0090] 2. Preparation method exploration:

[0091] The Chinese medicine composition for treating chronic renal failure provided by the present invention contains a large amount of bitter and cold medicines in its prescription, and the extract has a very strong bitter taste and is difficult to swallow. In addition, the extract contains polysaccharides, which are easy to absorb moisture and stick together after drying, resulting in a low preparation yield and difficulty in granulation.

[0092] Preparation method: 300g of Astragalus, 350g of Rhubarb Charcoal, 350g of Raw Rhubarb, 200g of Chuanxiong, 200g of Psoralea corylifolia, 1500g of Taraxacum mongolicum, 1500g of Stir-fried Cassia Seed, 200g of Citrus aurantium, and 600g of Scutellaria barbata.

[0093] Add 10 times the weight of water to the remaining eight medicinal materials except raw rhubarb into boiling water and boil for 2 hours, filter out the filtrate and residue; add raw rhubarb to the residue, add 9 times the weight of water and boil for 1.5 hours, filter out the filtrate and residue; combine the two filtrates, concentrate under reduced pressure at 50-60°C to a clear paste with a relative density of 1.03-1.10 (measured at 50°C), add sucralose, maltodextrin and sorbitol in proportion, mix well, spray dry, add microcrystalline cellulose and mix well, dry granulate, and calculate the preparation yield.

[0094] Table 4 Experimental results of different excipient addition schemes

[0095]

[0096] Considering that renal function of patients with chronic renal failure is often accompanied by symptoms such as diabetes, avoid choosing excipients that increase blood sugar and other excipients that may affect renal function when selecting excipients. Through the comparative study of different excipient formulas in Table 4, it is found that in the first excipient addition scheme, the combination of sucralose, sorbitol, and maltodextrin can better cover up the unique bitter taste of the Chinese medicine composition of the present invention and can slow down the moisture absorption of the material. Specifically, the combination of sucralose and sorbitol can better cover up the bitter taste of the medicine compared with other sweetener combinations; in addition, the combination of maltodextrin and sorbitol can better improve the moisture absorption of the material.

[0097] In order to further verify the effect of the ratio of sucralose, sorbitol, maltodextrin and microcrystalline cellulose in the auxiliary materials on the granules, the applicant of the present invention conducted an experimental study on the ratios of the five auxiliary materials in Table 5.

[0098] Table 5 Different proportions of auxiliary materials

[0099]

[0100]

[0101] Note: The proportion of auxiliary materials added in the table is the percentage of each auxiliary material added to the weight of the dry paste, and the weight of the dry paste is the dry weight of the clear paste.

[0102] The product was tested according to the test methods for solubility, particle size, etc. under the granules section of Part IV of the Chinese Pharmacopoeia (2020 edition), and the moisture absorption rate was determined by placing the product in an open weighing bottle (2g, 3mm) for 72 hours (temperature 25℃±2℃; relative humidity 75%±5%).

[0103] Table 6 Test results of granules with different excipient ratios

[0104] Inspection items Recipe 1 Recipe 2 Recipe 3 Recipe 4 Recipe 5 Appearance Uniform particles Moisture absorption, compaction, uneven particles Uniform particles Uneven particles Moisture absorption, compaction, uneven particles Solubility Failure qualified qualified qualified qualified Taste Too sweet Slightly bitter, astringent Moderate sweetness Slightly sweet Slightly bitter granularity qualified Failure qualified qualified Failure Preparation yield% 88.7 83.5 92.3 86.2 82.7 Moisture absorption rate % 8.2 12.6 7.3 6.7 7.1

[0105] Note:

[0106] The above research results show that after the four excipients are mixed in different proportions and added to the extract paste, the yield of the granules of formula 3 is the highest, and the moisture absorption rate is low, the particle size is uniform, and the fluidity is good. Among them, sucralose, sorbitol, and maltodextrin can synergistically mask the bitter taste of the composition of the present invention; sorbitol, maltodextrin, and microcrystalline cellulose can work together to better prevent the particles from agglomerating and absorbing moisture, and maintain a good particle size and fluidity, so that the granulation process is smooth. Therefore, this optimal formula combination can be used for scale-up production and clinical trial research.

[0107] 3. Clinical research

[0108] A clinical trial was conducted to study the effectiveness of the Chinese medicine composition for treating chronic renal failure.

[0109] 3.1 Clinical trial sample preparation:

[0110] 300g of Astragalus, 350g of Rhubarb Charcoal, 350g of Raw Rhubarb, 200g of Chuanxiong, 200g of Psoralea corylifolia, 1500g of Taraxacum mongolicum, 1500g of Stir-fried Cassia Seed, 200g of Citrus aurantium, and 600g of Scutellaria barbata.

[0111] Add 10 times the weight of water to the remaining eight medicinal materials except raw rhubarb into boiling water and boil for 2 hours, filter out the filtrate and residue; add raw rhubarb to the residue, add 9 times the weight of water and boil for 1.5 hours, filter out the filtrate and residue; combine the two filtrates, concentrate under reduced pressure at 50-60°C to a clear paste with a relative density of 1.03-1.10 (measured at 50°C), add 0.02% sucralose, 5% sorbitol and 10% maltodextrin based on the weight of the dry paste, mix evenly, spray dry, add 2% microcrystalline cellulose based on the weight of the dry paste, mix well, dry granulate, and bag. 6g / bag.

[0112] 3.2 Diagnostic criteria

[0113] 3.2.1 Western medicine diagnostic criteria

[0114] It complies with the staging and diagnostic criteria for chronic renal failure in the "Guidelines for the Diagnosis and Treatment of Chronic Renal Failure with Integrated Traditional Chinese and Western Medicine" (2023) and the "Guidelines for Early Screening, Diagnosis and Prevention of Chronic Kidney Disease (2022 Edition)".

[0115] 3.2.2 TCM symptom diagnosis criteria

[0116] The diagnosis is made according to the syndrome differentiation and classification standards proposed in the "Guidelines for the Diagnosis and Treatment of Chronic Renal Failure with Integrated Traditional Chinese and Western Medicine" (2023) jointly issued by the China Association of Traditional Chinese Medicine, the Chinese Society of Integrated Traditional Chinese and Western Medicine, and the Chinese Medical Association.

[0117] Table 7 Relationship between TCM syndrome differentiation and Western medicine clinical stage of CRF

[0118]

[0119] 3.3 Inclusion and Exclusion Criteria

[0120] Table 8 Inclusion and exclusion criteria for clinical cases

[0121]

[0122]

[0123] 3.4 General Information

[0124] The 32 subjects in this trial were all chronic renal failure patients who were followed up in the outpatient clinic of Hongjitang Chinese Medicine Hospital from September 2021 to September 2022. Among them, there were 19 males aged 41 to 66 years old and 13 females aged 43 to 70 years old. According to the syndrome differentiation of traditional Chinese medicine, 23 patients with deficiency of spleen and kidney yang were diagnosed as deficiency of both yin and yang, and 9 patients were diagnosed as deficiency of both yin and yang. The symptoms of excess syndrome were blood stasis in 32 cases, dampness in 21 cases, damp-heat in 27 cases, and drowning intoxication in 19 cases.

[0125] The 32 patients with chronic renal failure were treated with the same composition of Shenshuai Paidu Granules of the present invention, taken with boiled water, 3 times a day, 1 bag each time, 6 g / bag, for 12 consecutive weeks.

[0126] 3.5 Laboratory tests

[0127] 3.5.1 Efficacy indicators

[0128] Serum creatinine (SCr), urea nitrogen (BUN), hemoglobin (Hb), eGFR, and urine albumin / creatinine ratio (ACR).

[0129] 3.5.2 Safety indicators

[0130] Routine blood test, routine urine test, liver function test, kidney function test, electrolytes and electrocardiogram.

[0131] 3.6 Determination of TCM Syndrome Efficacy

[0132] Refer to the symptom grading quantitative table and efficacy judgment standard formulated in the "Guidelines for Clinical Research of New Chinese Medicines" in 2002. Among the three levels of symptoms, mild, moderate and severe, mild symptoms are scored 1 point, moderate symptoms are scored 2 points, and severe symptoms are scored 3 points. According to this standard, the TCM symptom scores such as chills and cold limbs, frequent urination at night, nausea and vomiting, limb numbness, uncomfortable bowel movements, itching all over the body, and facial and limb edema are given.

[0133] Efficacy criteria:

[0134] ① Significantly effective: clinical symptoms and signs of TCM are significantly improved, and the syndrome score is reduced by ≥70%;

[0135] ② Effective: TCM clinical symptoms and signs are improved, and the syndrome score is reduced by ≥30%;

[0136] ③ Ineffective: There is no significant improvement in TCM clinical symptoms and signs, or they may even get worse, and the syndrome score decreases by less than 30%.

[0137] (Calculation method = (total score before treatment - total score after treatment) / total score before treatment × 100%.)

[0138] 3.7 Results

[0139] 3.7.1 Effect of TCM symptoms after treatment

[0140] Table 9 Clinical TCM symptom efficacy results

[0141]

[0142] The results in Table 9 show that the Chinese medicine composition provided by the present invention has obvious therapeutic effects on the TCM symptoms of chronic renal failure patients with spleen and kidney yang deficiency and yin and yang deficiency type.

[0143] 3.7.2 Comparison of laboratory test indicators before and after treatment

[0144] The changes in SCr, BUN, eGFR, ACR and Hb levels before and after treatment are shown in the table below.

[0145] Table 10 Comparison of laboratory test indicators before and after treatment (n=32, )

[0146]

[0147] Note: Compared with before treatment, ▲ P<0.05,*P<0.01.

[0148] The research results in Table 10 show that after treatment with the composition of the present invention, the serum Scr level was significantly reduced (P < 0.01), and there were significant differences in ACR, eGFR, BUN, and Hb before and after treatment (P < 0.05). The present invention can significantly improve the renal function indicators of patients with chronic renal failure and also has a certain effect on increasing Hb.

[0149] The above specific implementation manner cannot be used as a limitation on the protection scope of the present invention. For those skilled in the art, any substitution, improvement or change made to the implementation manner of the present invention falls within the protection scope of the present invention.

[0150] The matters not described in detail in the present invention are all known technologies to those skilled in the art.

Claims

1. A Chinese medicine composition for treating chronic renal failure, characterized in that: The invention is prepared from the following raw materials in parts by weight: 2-4 parts of astragalus, 3-4 parts of rhubarb charcoal, 3-4 parts of raw rhubarb, 1-3 parts of chuanxiong, 1-3 parts of psoralea corylifolia, 12-15 parts of dandelion, 12-15 parts of stir-fried cassia seeds, 1-3 parts of aurantium and 5-7 parts of barbata scutellaria.

2. The Chinese medicine composition according to claim 1, characterized in that: The weight proportions of each raw material are: 3 parts of astragalus, 3.5 parts of rhubarb charcoal, 3.5 parts of raw rhubarb, 2 parts of chuanxiong, 2 parts of psoralea corylifolia, 15 parts of dandelion, 15 parts of stir-fried cassia seed, 2 parts of aurantium, and 6 parts of barbata scutellaria.

3. The Chinese medicine composition according to claim 1, characterized in that The extract of the Chinese medicine composition according to claim 1 or 2 is added to a pharmaceutically acceptable carrier to prepare an oral preparation, which is an oral liquid, granules, tablets, capsules or pills.

4. The Chinese medicine composition according to claim 3, characterized in that: The extract of the Chinese medicine composition is a water-extracted clear paste, the dried product of the water-extracted clear paste is a water-extracted dry paste, the oral preparation is a granule, and the carrier includes the following auxiliary materials in the following weight percentages of the water-extracted dry paste: 0.02% to 0.03% of sucralose, 4% to 6% of sorbitol, 9% to 11% of maltodextrin, and 1.8% to 2.0% of microcrystalline cellulose.

5. The method for preparing the Chinese medicine composition according to claim 4, characterized in that: The method comprises the following steps: adding sucralose, sorbitol and maltodextrin into the water-extracted clear paste, mixing evenly, spray drying, adding microcrystalline cellulose, mixing evenly, and dry granulating to obtain the granules of the traditional Chinese medicine composition.

6. The method for preparing the Chinese medicine composition according to claim 4, characterized in that: The preparation method of the water-extracted clear paste comprises the following steps: Mix the remaining raw materials except the raw rhubarb, add 8 to 12 times the weight of water, boil for 1 to 2 hours, and filter to obtain a residue and a filtrate; add the raw rhubarb to the residue, add 8 to 10 times the weight of water, boil for 0.5 to 1.5 hours, and filter to obtain a residue and a filtrate; The two filtrates were combined and concentrated under reduced pressure at 50-60°C to a water-extracted clear paste having a relative density of 1.03-1.10 measured at 50°C.

7. Use of the Chinese medicine composition according to any one of claims 1 to 4 in the preparation of drugs for treating chronic renal failure.

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