A Chinese medicine composition with anti-chronic renal failure effect and its preparation method and application

Abstract

The present invention relates to the technical field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for treating chronic renal failure, and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 5-40 parts of rhubarb, 5-30 parts of polygonatum, 5-30 parts of codonopsis, 10-40 parts of salvia miltiorrhiza, 5-40 parts of smilax glabra, 5-20 parts of oyster, 5-30 parts of fructus aurantii and 5-30 parts of liquorice. The present invention reasonably combines rhubarb, polygonatum, smilax glabra, salvia miltiorrhiza, oyster, fructus aurantii, liquorice and codonopsis according to traditional Chinese medicine theory and clinical practice, and the obtained composition has the effect of significantly reducing blood urea nitrogen, blood creatinine and urine protein, and has good market promotion value and medical application value.

Description

Technical Field

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

[0002] Chronic renal failure (CRF) refers to chronic progressive renal parenchymal damage caused by various reasons, which makes the kidney unable to maintain its basic functions, and presents a clinical syndrome with metabolic product retention, water, electrolyte, acid-base imbalance, and systemic involvement as the main manifestations. It is also called uremia. The main common causes of CRF in my country are: chronic glomerulonephritis, diabetic nephropathy, hypertensive renal arteriosclerosis, obstructive nephropathy, and systemic lupus erythematosus.

[0003] At present, chronic renal failure still lacks satisfactory treatment. For patients with end-stage renal disease, hemodialysis, peritoneal dialysis and kidney transplantation are mainly used for treatment. However, these treatments all have their inherent disadvantages. Due to high economic costs, long time consumption and complicated operation, only 15% of renal failure patients in the world can receive dialysis treatment, and there are many complications. Among the patients receiving dialysis, there are medical problems that have not yet been broken through. For patients with renal insufficiency but not meeting the dialysis standards, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) can be taken to delay the development of nephropathy. These two types of drugs mainly reduce high pressure, high perfusion and high filtration in the glomerulus, delay the deterioration of renal function, but some patients will still progress to end-stage renal disease. At present, there is a lack of effective therapeutic drugs for chronic renal failure. Therefore, it is urgent to develop a safe, effective and economical anti-chronic renal failure drug.

[0004] Chronic renal failure belongs to the category of "urinary retention" and "blockage" in traditional Chinese medicine. Wang Bichang of the Qing Dynasty said in "Medical Dialectics": "The swelling of water is first swollen in the abdomen, then the outside, and gradually the limbs are also swollen." If the bladder water channel cannot be unblocked, it is blocked. "Treatise on Febrile Diseases·Pingmai Method II": "Blocked means unable to urinate, blocked means vomiting." It is believed that this is caused by "turbid evil blocking the triple energizer, and the vital energy cannot rise and fall." With the extensive involvement of traditional Chinese medicine in the treatment of diseases, its superiority has gradually emerged, such as stable efficacy, few adverse reactions, and the ability to delay or reduce the occurrence of complications and improve the quality of life of patients. Therefore, the use of traditional Chinese medicine has become an important choice for the treatment of chronic kidney disease in my country.

[0005] Shenfushu Granules are a hospital preparation of the Second Xiangya Hospital of Central South University. It is based on six Chinese medicinal materials: rhubarb, salvia miltiorrhiza, licorice, smilax glabra, fructus aurantii, and oyster. They work together to play a comprehensive role in purging turbidity and dampness, promoting blood circulation and removing blood stasis. They can be used for various acute and chronic renal failure, azotemia, uremia, and elevated blood urea nitrogen caused by various reasons. However, Shenfushu Granules have some problems in clinical application, such as poor taste and poor compliance of some patients in long-term use; it has a good effect on reducing creatinine and urea nitrogen, but the effect of reducing urine protein needs to be improved. Therefore, we improved its formula based on the original prescription according to the theory of traditional Chinese medicine, achieving the purpose of improving quality and increasing efficiency. Summary of the invention

[0006] In view of this, the first purpose of the present invention is to provide a traditional Chinese medicine composition for treating chronic renal failure (the present invention is also referred to as a traditional Chinese medicine composition), aiming to improve the therapeutic effect of chronic renal failure based on a new mechanism of action of monarch, minister, assistant and envoy.

[0007] The second purpose of the present invention is to provide the preparation of the Chinese medicine composition and its application in the preparation of medicine for treating chronic renal failure.

[0008] The third object of the present invention is to provide a pharmaceutical preparation comprising the traditional Chinese medicine composition.

[0009] In order to achieve the above object, the present invention provides the following technical solutions:

[0010] The present invention provides a Chinese medicine composition for treating chronic renal failure, which is a herbal medicine composition and an extract thereof composed of the following raw materials in weight ratio:

[0011] 5-40 grams of rhubarb, 5-30 grams of polygonatum, 5-30 grams of codonopsis, 10-40 grams of salvia miltiorrhiza, 5-40 grams of wild yam, 5-20 grams of oyster, 5-30 grams of aurantium and 5-30 grams of licorice.

[0012] The present invention studies show that by combining the components and proportions, synergy can be achieved, blood urea nitrogen, blood creatinine and urine protein can be effectively reduced, and the treatment effect of chronic renal failure can be improved.

[0013] Preferably, the weight ratio of the raw materials in the Chinese medicine composition is:

[0014] 5-25 grams of rhubarb, 5-20 grams of polygonatum, 5-20 grams of codonopsis pilosula, 10-30 grams of salvia miltiorrhiza, 5-20 grams of wild yam, 5-10 grams of oyster, 5-20 grams of aurantium and 5-20 grams of licorice.

[0015] Preferably, 10-20 grams of rhubarb, 5-15 grams of polygonatum, 5-15 grams of codonopsis pilosula, 15-25 grams of salvia miltiorrhiza, 10-20 grams of smilax glabra, 5-10 grams of oyster, 5-15 grams of aurantium and 5-15 grams of liquorice.

[0016] The Chinese medicine composition of the present invention, the extract is a water extract of the herbal medicine composition.

[0017] The present invention also provides a method for preparing the Chinese medicine composition, and the raw materials are mixed according to the weight ratio to obtain the crude drug composition.

[0018] The preferred preparation method of the present invention comprises the steps of mixing the raw materials, extracting with water, filtering, concentrating the filtrate under reduced pressure, and spray drying to obtain the extract.

[0019] Preferably, the decoction extraction is performed 1 to 3 times, each decoction takes 1 to 1.5 hours, and the amount of water added in the decoction extraction is 6 to 8 times the total weight of the raw materials.

[0020] Preferably, the concentration is reduced-pressure concentration, and the reduced-pressure concentration is to concentrate the filtrate to a relative density of 1.10 to 1.15 at 60°C.

[0021] Preferably, the vacuum drying temperature is 55 to 60° C., and the vacuum degree is -0.07 to -0.08 MPa.

[0022] The present invention also provides the use of the Chinese medicine composition or the Chinese medicine composition prepared by the preparation method in preparing and treating chronic renal failure.

[0023] The present invention also provides a traditional Chinese medicine preparation for preventing and / or treating chronic renal failure, comprising the traditional Chinese medicine composition of the present invention and pharmaceutically acceptable adjuvants.

[0024] The pharmaceutically acceptable excipients of the present invention are excipients known in the industry, such as one or more of dextrin, stevioside, starch, lactose, mannitol, cellulose, etc.

[0025] In the present invention, the Chinese medicine preparation is granules, powders, decoctions, pills, tablets, capsules, and mixtures. Each of the above dosage forms can be prepared by selecting appropriate acceptable excipients according to the actual needs of the dosage form.

[0026] In the original formula (Shen Fu Shu Granule), rhubarb is the main drug for eliminating heat and toxicity, clearing stagnation, promoting blood stasis, and clearing the bowels and purging turbidity; smilax glabra detoxifies, dispels wind and dampness, and licorice nourishes the spleen and harmonizes the stomach, helping smilax glabra to strengthen the spleen, promote dampness, harmonize the stomach and reduce turbidity, and relieve rhubarb from damaging the stomach due to excessive cold, and protecting the middle qi from damage, which are the assistant drugs; Citrus aurantium promotes qi and promotes phlegm, and promotes the gathering of dampness in the middle jiao, oyster protects the kidney and astringes body fluid, treats the instability of kidney qi due to obstruction, and prevents rhubarb from excessively clearing turbidity, which are the adjuvant drugs; salvia miltiorrhiza promotes blood circulation and removes stasis, which is the guiding drug. All the drugs cooperate with each other to play a comprehensive role in purging turbidity, promoting dampness, promoting blood circulation and removing stasis. In the present invention, the dosage of rhubarb and liquorice in the original prescription is adjusted, and polygonatum and codonopsis are added; the coordination mechanism of the drug monarch, minister, assistant and envoy can be adjusted. For example, in the prescription described in the present invention, rhubarb is bitter and cold, clears the bowels and removes turbidity, removes blood stasis and detoxifies, codonopsis is sweet and flat, and invigorates the spleen and replenishes qi, which is the monarch drug; Citrus aurantium is bitter, pungent, and slightly cold, and regulates qi and relieves the middle, relieves stagnation and dissipates swelling, and helps rhubarb to strengthen the power of clearing the bowels and removing turbidity; salvia miltiorrhiza is bitter and slightly cold, and promotes blood circulation and removes blood stasis, and rhubarb is combined to strengthen the power of removing blood stasis; polygonatum is sweet and flat, nourishes the spleen and kidney, and helps codonopsis to enhance the effect of invigorating the spleen and tonifying the kidney, and the three drugs are all minister drugs; Smilax glabra is sweet, light, flat, removes dampness and detoxifies, and raw oyster is salty, astringent, and slightly cold, and dissipates stagnation and removes blood stasis, which are adjuvant drugs; and liquorice is sweet, slow, and invigorates the middle, and harmonizes the medicinal properties, which is the envoy drug. The whole prescription has the effects of invigorating the spleen and kidney, clearing the bowels and removing turbidity, and removing blood stasis and detoxifying.

[0027] Beneficial Effects

[0028] The invention reasonably combines rhubarb, polygonatum, smilax glabra, salvia miltiorrhiza, oyster, fructus aurantii, liquorice and codonopsis pilosula in accordance with traditional Chinese medicine theory and clinical practice. The obtained composition has significant effects of reducing blood urea nitrogen, blood creatinine and urine protein, and has good market promotion value and medical application value. DETAILED DESCRIPTION

[0029] The present invention discloses a Chinese medicine composition for treating chronic renal failure and its preparation method and application. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It should be particularly noted that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application described herein without departing from the content, spirit and scope of the present invention to realize and apply the technology of the present invention.

[0030] The disclosed embodiments are described to enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

[0031] The present invention will be further described below in conjunction with embodiments:

[0032] Example 1 Preparation of the Chinese medicine composition and granules of the present invention

[0033] Formula: 15 grams of rhubarb, 10 grams of polygonatum, 10 grams of codonopsis pilosula, 20 grams of salvia miltiorrhiza, 15 grams of smilax glabra, 5 grams of oyster, 10 grams of aurantium and 10 grams of liquorice.

[0034] Preparation method: weigh the above eight Chinese medicines in proportion, add water and decoct twice, add 8 times of water for the first time and decoct for 1.5 hours; add 6 times of water for the second time and decoct for 1 hour, filter, combine the filtrate, and concentrate under reduced pressure to a thick paste with a relative density of about 1.10 to 1.15 (measured at 60°C), vacuum dry (drying temperature is 55 to 60°C, vacuum degree is -0.07 to -0.08Mpa), and spray dry to obtain the composition of the present invention.

[0035] Add dextrin, stevioside and 90% ethanol to the dry paste powder, granulate (16 mesh sieve), dry at 55° C. to 60° C., granulate (16 mesh sieve) to obtain the finished product.

[0036] Comparative Example 1 Preparation of the Chinese medicine composition and granules of the present invention

[0037] Formula: 15 grams of rhubarb, 0 grams of polygonatum, 0 grams of codonopsis, 20 grams of salvia miltiorrhiza, 15 grams of smilax glabra, 5 grams of oyster, 10 grams of aurantium and 10 grams of liquorice.

[0038] Preparation method: weigh the above six Chinese medicines in proportion, add water and decoct twice, add 8 times of water for the first time, and decoct for 1.5 hours; add 6 times of water for the second time, decoct for 1 hour, filter, combine the filtrate, and concentrate under reduced pressure to a thick paste with a relative density of about 1.10 to 1.15 (measured at 60°C), vacuum dry (drying temperature is 55 to 60°C, vacuum degree is -0.07 to -0.08Mpa), and spray dry to obtain the composition of the present invention.

[0039] Add dextrin, stevioside and 90% ethanol to the dry paste powder, granulate (16 mesh sieve), dry at 55° C. to 60° C., granulate (16 mesh sieve) to obtain the finished product.

[0040] Comparative Example 2 Preparation of the Chinese medicine composition and granules of the present invention

[0041] Formula: 15 grams of rhubarb, 10 grams of polygonatum, 0 grams of codonopsis pilosula, 20 grams of salvia miltiorrhiza, 15 grams of smilax glabra, 5 grams of oyster, 10 grams of aurantium and 10 grams of liquorice.

[0042] Preparation method: weigh the above seven Chinese medicines in proportion, add water and decoct twice, add 8 times of water for the first time and decoct for 1.5 hours; add 6 times of water for the second time and decoct for 1 hour, filter, combine the filtrate, and concentrate under reduced pressure to a thick paste with a relative density of about 1.10 to 1.15 (measured at 60°C), vacuum dry (drying temperature is 55 to 60°C, vacuum degree is -0.07 to -0.08Mpa), and spray dry to obtain the composition of the present invention.

[0043] Add dextrin, stevioside and 90% ethanol to the dry paste powder, granulate (16 mesh sieve), dry at 55° C. to 60° C., granulate (16 mesh sieve) to obtain the finished product.

[0044] Comparative Example 3 Preparation of the Chinese medicine composition and granules of the present invention

[0045] Formula: It is made of the following Chinese medicines in parts by weight: 15 parts of rhubarb, 0 parts of polygonatum, 10 parts of codonopsis pilosula, 20 parts of salvia miltiorrhiza, 15 parts of smilax glabra, 5 parts of oyster, 10 parts of fructus aurantii and 10 parts of liquorice.

[0046] Preparation method: weigh the above seven Chinese medicines in proportion, add water and decoct twice, add 8 times of water for the first time and decoct for 1.5 hours; add 6 times of water for the second time and decoct for 1 hour, filter, combine the filtrate, and concentrate under reduced pressure to a thick paste with a relative density of about 1.10 to 1.15 (measured at 60°C), vacuum dry (drying temperature is 55 to 60°C, vacuum degree is -0.07 to -0.08Mpa), and spray dry to obtain the composition of the present invention.

[0047] Add dextrin, stevioside and 90% ethanol to the dry paste powder, granulate (16 mesh sieve), dry at 55° C. to 60° C., granulate (16 mesh sieve) to obtain the finished product.

[0048] Example 2 Effects of different combinations on 5 / 6 nephrectomy-induced chronic renal failure model rats

[0049] 2.1 Experimental Purpose

[0050] This study used a chronic renal failure model induced by 5 / 6 nephrectomy and intragastric administration of each formula to evaluate the main pharmacodynamics of each formula, providing an experimental basis for clinical application.

[0051] 2.2 Experimental Materials

[0052] 2.2.1 Drugs and reagents

[0053] Shenfushu granules, clinical dosage: 95g crude drug / day; provided by: Second Xiangya Hospital of Central South University. The crude drugs of Shenfushu include rhubarb, salvia miltiorrhiza, smilax glabra, oyster, fructus aurantii and licorice in a weight ratio of 25:20:15:5:10:20, and the granules are prepared by a water extraction method similar to that in the embodiment.

[0054] Composition I (granules prepared in comparative example 1), clinical dosage: 75 g crude drug / day. Provider: The Second Xiangya Hospital of Central South University.

[0055] Composition II (granules prepared in comparative example 2), clinical dosage: 85 g crude drug / day. Provider: The Second Xiangya Hospital of Central South University.

[0056] Composition III (granules prepared in comparative example 3), clinical dosage: 85 g crude drug / day. Provider: The Second Xiangya Hospital of Central South University.

[0057] Composition IV (granules prepared in Example 1), clinical dosage: 95 g crude drug / day. Provider: The Second Xiangya Hospital of Central South University.

[0058] Urea Clearing Granules, batch number: 20181163. Specification: 5g / bag. Provider: Kangchen Pharmaceutical Co., Ltd.

[0059] Note: In the present invention, unless otherwise stated, the Shenfushu granules mentioned refer to granules made from the same raw materials and preparation batches.

[0060] 2.2.2 Animals and feed

[0061] SD rats, 220.0-250.0 g, 80 rats, male, SPF grade. Supplier: Hunan Slake Jingda Experimental Animal Co., Ltd. Laboratory Animal Use License No.: SYXK (Xiang) 2017-0002.

[0062] 2.2.3 Instruments

[0063] Electronic balance, Sunny Hengping Instrument. Fully automatic biochemical analyzer, FAITH-1000. Rat metabolic cage, Suzhou Fengshi Experimental Animal Equipment Co., Ltd.

[0064] 2.3 Dosage design

[0065] 2.3.1 Drug preparation and dosage

[0066] The clinical adult dosage of Shenfushu Granules, Compositions II, III, and IV is 95 g of crude drug per day, and the clinical adult dosage of Composition I and IV is 75 g of crude drug per day, respectively. According to the "Pharmacological Experimental Methodology" edited by Wei Wei, the fourth edition, page 1698, the conversion table of equivalent doses between animal species and body surface area, the rat clinical equivalent dose = adult dose × 0.018 × 5, the equivalent doses of Shenfushu Granules group, Composition I, Composition II, Composition III and Composition IV are 8.55 g / kg, 6.75 g / kg, 7.65 g / kg, 7.65 g / kg and 8.55 g / kg, respectively. The equivalent dose of Urea Clearing Granules group is 7.20 g / kg, and the dosages of each group are shown in Table 1

[0067] Table 1 Dosage table of prescription

[0068]

[0069] 2.3.2 Drug preparation

[0070] Shenfushu granule group: 7.00 g of the composition extract was weighed, ground, and fixed to 40 ml (0.175 g / ml) with water.

[0071] Composition Group I: 7.08 g of the extract was weighed, ground, and made up to 40 ml (0.177 g / ml) with water.

[0072] Composition Group II: Weigh 7.37 g of the extract, grind it, and add water to make up to 40 ml (0.184 g / ml).

[0073] Composition Group III: 6.76 g of the extract was weighed, ground, and made up to 40 ml (0.169 g / ml) with water.

[0074] Composition Group IV: 6.68 g of the extract was weighed, ground, and made up to 40 ml (0.167 g / ml) with water.

[0075] Uridine Clearing Granules: Weigh 28.8 g of Uridine Clearing Granules, grind, and add water to make up to 80 ml (0.360 g / ml).

[0076] 2.3.3 Routes and methods of administration

[0077] Oral administration: the same route as that used in clinical practice.

[0078] Dosing volume: 10ml / kg, 20ml / kg.

[0079] Dosage frequency and time: once a day.

[0080] Dosing duration: 4 weeks.

[0081] Medication operation: Follow the relevant SOP requirements.

[0082] 2.4 Methods

[0083] 2.4.1 Effect of the composition on nephrotic rats induced by 5 / 6 nephrectomy

[0084] 90 SD rats, except for 10 blank control groups and 10 sham operation groups, 70 SD rats were used for modeling, and kidney removal was performed in two steps: 8% chloral hydrate intraperitoneal injection anesthesia, routine skin disinfection, abdominal incision to fully expose the right kidney, peeling the renal capsule, surgical ligation and removal of the entire right kidney. One week after the first operation, 2 / 3 of the left kidney was removed, medical gelatin sponge was used to compress and stop bleeding, and the wound was sutured. A total of 5 / 6 of all kidneys were removed in both surgeries, and antibiotics were given for 3 days after surgery. The same steps were taken for 10 rats in the sham operation group, but no nephrectomy was performed. The 10 rats in the blank control group were not treated. The 70 rats with successful modeling were selected and divided into model control group, Shenfushu granule group, combination group I, combination group II, combination group III, combination group IV and Urea Clearing Granule group, with 10 rats in each group. Oral administration, the administration volume was 10ml / kg. The administration volume of the Urea Clearing Granule group was 20ml / kg, once a day, for 4 consecutive weeks. The blank control group, sham operation group and model control group were given the same volume of distilled water.

[0085] 2.4.2 Observation indicators

[0086] 1) Body weight: The body weight of rats was measured before and after modeling.

[0087] 2) Blood urea nitrogen (BUN), creatinine (Cr) and 24-h urine protein: Urine and blood were collected before administration and 4 weeks after administration to measure the BUN and Cr levels in serum and the 24-h urine protein level in urine.

[0088] 2.4.3 Statistical analysis methods

[0089] SPSS17.0 software was used for statistical analysis. All data were expressed as Mean±SD. The data between two groups were analyzed using t-test. The comparison between multiple groups (≥3) was analyzed using Student-Newman-Keuls' t (SNK) analysis and Tukey's test. P<0.05 was considered statistically significant.

[0090] 2.5 Results

[0091] 2.5.1 Effects on rat body weight

[0092] Compared with the blank control group, the body weight of rats in the model control group and each drug-treated group was significantly reduced (P<0.05), indicating that partial nephrectomy has an effect on the body weight of animals; compared with the model control group, the body weight of the combination group I was not affected after 1, 2, 3, and 4 weeks of administration, and the body weight of the Urea Clearing Granule group was significantly increased after 4 weeks of administration (P<0.05), and the body weight of the other groups showed a trend of recovery after administration. The results are shown in Table 2.

[0093] Table 2 Effects of the formula on the body weight of rats

[0094]

[0095]

[0096] Note: Compared with the blank control group, * P<0.05, ** P<0.01, *** P<0.001; compared with the model control group, ΔP<0.05.

[0097] 2.5.2 Effects of each prescription on serum Cr and BUN levels in rats with renal failure

[0098] Compared with the blank control group, the serum Cr levels of the model control group and each drug-treated group before administration were significantly increased (P<0.01). Compared with the model control group, the serum Cr levels of the Shenfushu granule group, the combination group I, the combination group II, the combination group III and the Shenshuaining group were significantly reduced after 4 weeks of administration (P<0.05), among which the degree of reduction in the combination group III was greater. The results are shown in Table 3. Compared with the blank control group, the serum BUN levels of the model control group and each drug-treated group before administration were significantly increased (P<0.01). Compared with the model control group, the serum BUN levels of the Shenfushu granule group, the combination group I, the combination group II, the combination group III and the Shenshuaining group were significantly reduced after 4 weeks of administration (P<0.05). The results are shown in Table 3. In addition, compared with the Shenfushu granule group, the effect of the combination group I was similar to that of the Shenfushu granule group, indicating that reducing the dose of rhubarb and licorice had no significant effect on their activity.

[0099] Table 3 Effects of the prescription on serum Cr and BUN

[0100]

[0101]

[0102] Note: Compared with the blank control group, *** P<0.001; compared with the model control group, ΔP<0.05, ΔΔP<0.01, ΔΔΔP<0.001.

[0103] 2.5.3 Effects of each component on 24-h urine protein content in rats with renal failure

[0104] Compared with the blank control group, the 24-h urine protein level of rats in the model control group and the experimental group before administration was significantly increased (P<0.01); compared with the model control group, the 24-h urine protein level of rats in each experimental group was significantly reduced after 4 weeks of administration (P<0.05), and the effect of reducing urine protein in the composition IV group was better than that in other groups. The results are shown in Table 4.

[0105] Table 4 Effect of the formula on urine protein

[0106]

[0107] Note: Compared with the blank control group, *** P<0.001; compared with the model control group, ΔP<0.05, ΔΔP<0.01, ΔΔΔP<0.001.

[0108] 2.6 Conclusion

[0109] Under the experimental conditions, each group of prescriptions can reduce the increase in serum creatinine and blood urea nitrogen levels in 5 / 6 nephrectomized rats, and reduce the content of 24-h urinary protein in the urine of 5 / 6 nephrectomized rats; among them, the effect of combination IV in reducing urinary protein is better than the original prescription.

[0110] Example 3 Effect of each component particle on taste

[0111] 3.1 Experimental Materials

[0112] 3.1.1 Drugs and reagents

[0113] Shenfushu granules (same as Example 2), intended clinical dosage: 95 g crude drug / day; provider: The Second Xiangya Hospital of Central South University.

[0114] Composition group I (same as Example 2), clinical dosage: 75 g crude drug / day. Provider: The Second Xiangya Hospital of Central South University.

[0115] Composition II (same as Example 2), clinical dosage: 85 g crude drug / day. Provider: The Second Xiangya Hospital of Central South University.

[0116] Composition group III (same as Example 2), clinical dosage: 85 g crude drug / day. Provider: The Second Xiangya Hospital of Central South University.

[0117] Composition group IV (same as Example 2), clinical dosage: 95 g crude drug / day. Provided by: The Second Xiangya Hospital of Central South University

[0118] Urea Clearing Granules, batch number: 20181163. Specification: 5g / bag. Provider: Kangchen Pharmaceutical Co., Ltd.

[0119] 3.2 Methods

[0120] Shenfushu granules, formula I, II, III and IV, and Urea Clearing Granules were dissolved in 100 ml of water and tasted by 10 volunteers (5 men and 5 women) to rate the overall taste, bitterness and spiciness of the products. Weighted average score: the weight of overall taste is 40%, the weight of bitterness is 30%, and the weight of spiciness is 30%. The weighted score is calculated as follows: K = R1 × 40% + R2 × 30% + R3 × 30%.

[0121] 3.3 Data processing

[0122] SPSS17.0 software was used for statistical analysis. All data were expressed as Mean±SD. The data between two groups were analyzed using t-test. The comparison between multiple groups (≥3) was analyzed using Student-Newman-Keuls' t (SNK) analysis and Tukey's test. P<0.05 was considered statistically significant.

[0123] 3.4 Results

[0124] The weighted scoring results showed that the granules of each formula could improve the taste compared with the original formula (P<0.05), see Table 5.

[0125] Table 5 Taste test evaluation

[0126]

[0127] Note: Compared with Shenfushu Granules, * P<0.05, ** P<0.01, *** P<0.001.

[0128] 3.5 Conclusion

[0129] The above experimental results show that under the experimental conditions, the new formula can improve the overall taste of the original prescription.

[0130] Example 4 Effect of the present invention on adenine-induced chronic renal failure model rats

[0131] On the basis of Example 2, the inventors continued to verify the efficacy of Composition IV in adenine-induced chronic renal failure rat model.

[0132] Experimental Materials

[0133] 4.1.1 Drugs and reagents

[0134] Shenfushu granules (same as Example 2), intended clinical dosage: 95 g crude drug / day; provider: The Second Xiangya Hospital of Central South University.

[0135] Composition group IV (same as Example 2), clinical dosage: 95 g crude drug / day. Provided by: The Second Xiangya Hospital of Central South University

[0136] Urea Clearing Granules, batch number: 20181163. Specification: 5g / bag. Provider: Kangchen Pharmaceutical Co., Ltd.

[0137] 4.1.2 Animals and feed

[0138] SD rats, 220.0-250.0g, 60 rats, male. Supplier: Hunan Slake Jingda Experimental Animal Co., Ltd. Laboratory Animal Production License No.: SCXK (Xiang) 2016-0002. Laboratory Animal Use License No.: SYXK (Xiang) 2014-0012. Laboratory Animal Quality Certificate No.: No.43004700056858. Laboratory Animal Facility Use Certificate: 00092165. SPF rat feed is irradiated feed, produced by Hunan Slake Jingda Experimental Animal Co., Ltd., license No. SCXK (Xiang) 2014-0002, in accordance with GB 14923.2-2001 and GB 14923.3-2010 standards. Packaging: vacuum packaging, 2.5kg per bag. Confirmation of feed quality: Refer to the national standards of the People's Republic of China GB14923.2-2001 and GB 14923.3-2010, and the supplier will conduct testing. Each batch of feed will be tested once. Feeding method: Feed according to the company's relevant SOP regulations, add feed at the right time every day, and ensure that the animals can eat freely. Laboratory animal use license number: SYXK (Xiang) 2011-0004. Quarantine weighing: Weigh the experimental animals when they are received. Weighing instrument: ES-1000E electronic balance. Quarantine location: Barrier environment quarantine observation room of Hunan Slake Jingda Laboratory Animal Co., Ltd. During the quarantine period, technicians will observe and record the appearance and general condition of the animals every day. If the animals are abnormal or weak, which may affect the experiment, they should be eliminated and shall not be used in the experiment.

[0139] 4.1.3 Instruments

[0140] Electronic balance, Changsha Xiangping Technology Co., Ltd. Syringe, Shengguang Medical Products Co., Ltd. Gastric gavage, Dongxi Instrument (Beijing) Technology Co., Ltd. Blood cell analyzer, BOULE EXIGO, Sweden. Fully automatic biochemical analyzer, FAITH-1000.

[0141] 4.1.4 Instruments

[0142] Mettler AB204 and PB1502 electronic balances (Switzerland); LBY-N6Cmtac fully automatic blood rheology system, Beijing Prism Biotechnology Co., Ltd.; EL3120 MICROPLA enzyme label detector (USA).

[0143] 4.2 Dosage design

[0144] 4.2.1 Drug preparation and dosage

[0145] See 5.3.1.

[0146] 4.2.2 Drug preparation

[0147] See 5.3.1.

[0148] 4.2.3 Routes and methods of administration

[0149] See 5.3.1.

[0150] Methods

[0151] 4.3.1 Experimental methods

[0152] SD rats, male, 60, except for 15 blank control groups, the remaining 45 SD rats, once a day, for 3 consecutive weeks, to prepare adenine-induced chronic renal failure model. After 3 weeks, the rats were fasted for 12h, and 5 rats in the blank control group and the modeling group were taken to take blood to determine the serum BUN and Cr levels. The significant difference in serum BUN and Cr levels between the model control group and the normal control group was used as a sign of successful modeling. 40 SD rats with successful modeling were selected and randomly divided into 4 groups, namely: model control group, Shenfushu granule group (8.55g crude drug / kg), combination group IV (8.55g crude drug / kg) and Urea Clearing Granule group (4.5g / kg), 10 in each group. Oral administration, the administration volume was 10ml / kg, and the administration volume of the Urea Clearing Granule group was 20ml / kg, once a day, for 4 consecutive weeks. Urine and blood were collected before, 2 weeks and 4 weeks after administration, and the Cr and BUN levels in serum and the 24-h urine protein content in urine were determined. After the last administration, the rats were killed, and the kidneys on both sides were weighed to calculate the kidney coefficient.

[0153] 4.3.2 Statistical analysis methods

[0154] SPSS17.0 software was used for statistical analysis. All data were expressed as Mean±SD. The data between two groups were analyzed using t-test. The comparison between multiple groups (≥3) was analyzed using Student-Newman-Keuls' t (SNK) analysis and Tukey's test. P<0.05 was considered statistically significant.

[0155] 4.4 Results

[0156] 4.4.1 Effects on serum BUN, Cr levels and kidney coefficient

[0157] Compared with the blank control group, the serum BUN (Table 6) and Cr (Table 7) levels in the model control group before administration were significantly increased (P<0.01); compared with the model control group, the serum BUN level of Shenfushu granules and combination IV was significantly reduced after 4 weeks of administration (P<0.05), and the Cr level was also significantly reduced (P<0.01), while there was no significant difference between Shenfushu granules and combination IV. Compared with the blank control group, the kidney coefficient of rats in the model group was significantly increased (P<0.01, Table 7); compared with the model control group, Shenfushu granules, combination IV and Urea Clearing Granules had no effect on the kidney coefficient (P<0.01).

[0158] Table 6 Effect of the prescription on serum BUN

[0159]

[0160] Note: Compared with the blank control group, ** P<0.01, *** P<0.001; compared with the model control group, ΔΔΔ P<0.001.

[0161] Table 7 Effects of the prescription on serum Cr and kidney coefficient

[0162]

[0163]

[0164] Note: Compared with the blank control group, *** P<0.001; compared with the model control group, ΔΔΔ P<0.001.

[0165] 4.4.2 Effect on urine protein content

[0166] Compared with the blank control group, the 24-h urine protein content of rats in the model control group was significantly increased (P<0.01); compared with the model control group, the composition IV could reduce the 24-h urine protein content after 4 weeks of administration (P<0.01). The results are shown in Table 8.

[0167] Table 8 Effect of the formula on urine protein

[0168]

[0169] Note: Compared with the blank control group, *P<0.05, **P<0.01, ***P<0.001; compared with the model control group, ΔΔ P<0.01.

[0170] Summary

[0171] Under the experimental conditions, the formula of the present invention (composition group IV) can reduce the serum BUN and Cr content and 24-h urine protein increased by adenine, and its effect is better than that of the primary (Shenfushu granule group). It suggests that the formula has a certain therapeutic effect on chronic renal failure caused by adenine.

[0172] Example 5 Effect of the present invention on blood rheology in rats with cold coagulation and blood stasis model

[0173] 5.1 Experimental Purpose:

[0174] This study selected SD rats and administered the drug by gavage to observe the effect of Formula Ⅳ on the hemorheology of rats with cold coagulation and blood stasis syndrome.

[0175] 5.2 Experimental Materials

[0176] 5.2.1 Drugs

[0177] Composition group IV (same as Example 2), clinical dosage: 95 g crude drug / day. Provided by: The Second Xiangya Hospital of Central South University

[0178] Shenfushu granules (same as Example 2), intended clinical dosage: 95 g crude drug / day; provider: The Second Xiangya Hospital of Central South University.

[0179] Urea Clearing Granules, batch number: 20181163. Specification: 5g / bag. Provider: Kangchen Pharmaceutical Co., Ltd.

[0180] 5.2.2 Animals

[0181] SD rats, 220.0-250.0g, 50 rats, male. Supplier: Hunan Slake Jingda Experimental Animal Co., Ltd. Laboratory Animal Production License No.: SCXK (Xiang) 2016-0002. Laboratory Animal Use License No.: SYXK (Xiang) 2014-0012. Laboratory Animal Quality Certificate No.: No.43004700056858. Laboratory Animal Facility Use Certificate: 00092165. SPF rat feed is irradiated feed, produced by Hunan Slake Jingda Experimental Animal Co., Ltd., license No. SCXK (Xiang) 2014-0002, in compliance with GB 14923.2-2001 and GB 14923.3-2010 standards.

[0182] 5.3 Methods

[0183] 50 SD rats were randomly divided into 5 groups, blank control group, model control group, Shenfushu granule group (8.55g crude drug / kg) group, combination IV (8.55g crude drug / kg), and Urea Clearing Granule group (4.5g / kg), 10 rats in each group, and intragastric administration, the administration volume was 10ml / kg, and the Urea Clearing Granule group was 20ml / kg, once / day, for 7 consecutive days. 1 hour after administration on the 6th and 7th days, 0.6mg / kg of adrenaline hydrochloride injection was subcutaneously injected, and the rats were immersed in ice water (0-2℃) for 30min. 4 hours later, adrenaline hydrochloride injection was injected again to create a rat cold coagulation blood stasis syndrome model. Blood was collected from the abdominal aorta the next day to measure the blood rheology (whole blood viscosity, plasma viscosity) of the rats.

[0184] 5.3.1 Statistical analysis methods

[0185] SPSS17.0 software was used for statistical analysis. All data were expressed as Mean±SD and subjected to one-way analysis of variance. P<0.05 was considered statistically significant.

[0186] 5.4 Effect of experimental results on hemorheological parameters of rats with cold stagnation and blood stasis syndrome

[0187] Compared with the blank control group, the low, medium and high shear values ​​of whole blood viscosity and plasma viscosity of rats in the cold stagnation and blood stasis syndrome model control group were significantly increased (P<0.01); compared with the model control group, the Shenfushu granule group, the combination IV and the Urea Clearing Granules group could reduce the low, medium and high shear values ​​of whole blood viscosity and plasma viscosity of rats (P<0.01). The results are shown in Table 9.

[0188] Table 9 Effects on blood rheology in rats with cold stagnation and blood stasis syndrome

[0189]

[0190] Note: Compared with the blank control group, ***P<0.001; compared with the model control group, ΔΔΔ P<0.001.

[0191] 5.5 Conclusion

[0192] Under the experimental conditions, both Shenfushu granules and composition IV can reduce whole blood viscosity and plasma viscosity, indicating that the prescription has the effect of promoting blood circulation and removing blood stasis. In addition, there is no significant difference between Shenfushu granules and composition IV (P>0.05).

[0193] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating chronic renal failure, characterized in that: A herbal medicine composition or an extract thereof composed of the following raw materials in weight ratio: Rhubarb 10 ~ 20, Polygonatum 5 ~ 15, Codonopsis pilosula 5 ~ 15, Salvia miltiorrhiza 15 ~ 25, Smilax glabra 10 ~ 20, Oyster 5 ~ 10, Citrus aurantium 5 ~ 15, and Licorice 5 ~ 15.

2. The Chinese medicine composition according to claim 1, characterized in that: The extract is a water extract of the herbal medicine composition.

3. A method for preparing the Chinese medicine composition according to any one of claims 1 to 2, characterized in that: The raw materials are mixed according to the weight ratio.

4. The method for preparing the Chinese medicine composition according to claim 3, characterized in that: The raw materials are mixed, extracted with water, filtered, and the filtrate is concentrated under reduced pressure and spray-dried to obtain the product.

5. The preparation method according to claim 4, characterized in that: The water extraction is water decoction extraction, the water decoction extraction times are 1 to 3 times, each decoction is 1 to 1.5 hours, and the amount of water added in the water decoction extraction is 6 to 8 times the total weight of the raw materials.

6. The preparation method according to claim 4, characterized in that: The reduced pressure concentration is to concentrate the filtrate to a relative density of 1.10 to 1.15 at 60°C.

7. Use of the Chinese medicine composition according to any one of claims 1 to 2 or the Chinese medicine composition prepared by the preparation method according to any one of claims 3 to 6 in the preparation of a preparation for treating chronic renal failure.

8. A Chinese medicine preparation for treating chronic renal failure, characterized in that: It comprises the Chinese medicine composition according to any one of claims 1 to 2 and pharmaceutically acceptable excipients.

9. The Chinese medicine preparation according to claim 8, characterized in that: The Chinese medicine preparation is in the form of granules, powders, decoctions, pills, tablets, capsules, mixtures or syrups.

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