A traditional Chinese medicine composition for treating chronic nephritis hematuria and a preparation method thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating chronic nephritis hematuria and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine preparation. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 18-22 parts of Astragalus membranaceus, 10-14 parts of female ligustrum lucidum, 10-14 parts of euphorbia humifusa, 10-14 parts of panax notoginseng, 2-4 parts of rhizoma cimicifugae, 18-22 parts of herba viola, 18-22 parts of rubia cordifolia, 1-3 parts of vinegar schisandra, 5-7 parts of gold cherry fruit, 5-7 parts of gordon euryale seed and 5-7 parts of calcined oyster shell. The traditional Chinese medicine composition for treating chronic nephritis hematuria can reduce the serum creatinine, urea nitrogen and urine protein levels of a nephritis hematuria model rat, plays a kidney function protection role, reduces the number of red blood cells in urine and the whole blood viscosity, plays a blood-activating and stasis-removing hemostatic role, can obviously improve the hematuria symptoms of the rat, and the symptoms are stable after drug withdrawal and no rebound phenomenon occurs.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine composition for treating hematuria in chronic nephritis and its preparation method, belonging to the field of traditional Chinese medicine preparation technology. Background Technology

[0002] Hematuria refers to the presence of red blood cells in the urine, and can be divided into gross hematuria and microscopic hematuria. It is a common symptom of chronic glomerulonephritis (CGN), and is a symptom of blood excreted from the kidneys in the urine after ruling out extrarenal bleeding factors such as stones, tuberculosis, tumors, and urinary tract infections. The causes of hematuria in CGN are complex, and there is no unified theory on its pathogenesis. Currently, modern medicine has no specific or targeted drugs for the treatment of hematuria in CGN. Traditional Chinese medicine (TCM) uses syndrome differentiation and treatment as its basic principles for diagnosing and treating diseases. TCM believes that the pathogenesis of hematuria in CGN is rooted in spleen and kidney deficiency, with damp-heat, turbid toxins, and blood stasis as manifestations. Kidney deficiency and impaired astringency are the root causes. The *Zhu Bing Yuan Hou Lun* states, "Consumption and exhaustion lead to the loss of essence and blood; this is because of the damage to kidney qi..." indicating that the direct cause of hematuria is the depletion of kidney qi. The kidneys are responsible for storing essence and blood. When the kidney qi is damaged, the ability to store essence and blood is impaired, leading to the leakage of essence and blood. In addition, spleen deficiency leads to the inability to control blood, causing blood that has left the normal channels to flow out, thus resulting in hematuria.

[0003] The existing Chinese patent medicines for treating chronic nephritis include compound nephritis tablets, nephritis recovery tablets, nephritis relief capsules, and nephritis tablets. They are mainly used for comprehensive treatment of various symptoms related to different types of nephritis. However, their efficacy in treating hematuria symptoms of nephritis alone is not outstanding. Therefore, there is currently a lack of Chinese patent medicines that specifically treat hematuria in chronic nephritis.

[0004] It should be noted that the above content falls within the inventor's technical knowledge and does 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 traditional Chinese medicine composition for treating hematuria in chronic nephritis and its preparation method. It can not only promote blood circulation and remove blood stasis, cool blood and stop bleeding to treat the symptoms, but also tonify the spleen and strengthen the kidney to treat the root cause. It is an effective prescription for treating hematuria in chronic nephritis.

[0006] The present invention achieves the above objectives by adopting the following technical solutions:

[0007] A traditional Chinese medicine composition for treating hematuria in chronic nephritis, made from the following raw materials in parts by weight:

[0008] Astragalus membranaceus 18-22 parts, Ligustrum lucidum (processed with wine) 10-14 parts, Eclipta prostrata 10-14 parts, Panax notoginseng 10-14 parts, Cimicifuga foetida 2-4 parts, Agrimonia pilosa 18-22 parts, Rubia cordifolia 18-22 parts, Schisandra chinensis (processed with vinegar) 1-3 parts, Rosa laevigata (processed with vinegar) 5-7 parts, Euryale ferox 5-7 parts, Calcined oyster shell 5-7 parts.

[0009] In a preferred embodiment, the weight parts of each raw material are as follows: 20 parts Astragalus membranaceus, 12 parts Ligustrum lucidum (processed with wine), 12 parts Eclipta prostrata, 12 parts Panax notoginseng, 3 parts Cimicifuga foetida, 20 parts Agrimonia pilosa, 20 parts Rubia cordifolia, 2 parts Schisandra chinensis (processed with vinegar), 6 parts Rosa laevigata, 6 parts Euryale ferox, and 6 parts Calcined Ostrea gigas.

[0010] Furthermore, the extract of the traditional Chinese medicine composition for treating hematuria in chronic nephritis provided by the present invention can be added to a pharmaceutically acceptable carrier to prepare an oral preparation, which may be an oral liquid, granules, tablets, capsules or pills.

[0011] Furthermore, the present invention provides one method for preparing the traditional Chinese medicine composition for treating hematuria in chronic nephritis, comprising the following steps:

[0012] S1. Grind Panax notoginseng into a fine powder of 80-100 mesh to make Panax notoginseng powder;

[0013] S2. Add 10-15 times the weight of water to the remaining raw materials, heat to boiling, and continue to decoct for 2-3 hours. Filter, add 8-12 times the weight of water to the dregs, and continue to decoct for 1-2 hours. Filter, combine the two filtrates, concentrate the filtrate under reduced pressure to 55℃-60℃ to obtain a clear extract with a relative density of 1.04-1.10, spray dry to obtain spray-dried powder.

[0014] S3. Spray-dried powder and Panax notoginseng powder are mixed evenly to prepare the traditional Chinese medicine composition for treating hematuria in chronic nephritis.

[0015] Furthermore, the present invention also provides another method for preparing the traditional Chinese medicine composition for treating hematuria in chronic nephritis, comprising the following steps:

[0016] (1) Grind Panax notoginseng into coarse powder, add 6 to 8 times its weight of 60% to 70% ethanol and soak for 24 hours. Percolate at a flow rate of 5 to 7 ml / min per kilogram of coarse powder and collect the percolate. Concentrate the percolate under reduced pressure at 50 to 60°C to remove the ethanol, filter, and obtain Panax notoginseng concentrated extract and filter residue.

[0017] Add 6 to 8 times the weight of water to the filter residue, soak at 40 to 50°C for 8 to 12 hours, filter, combine the filtrates, concentrate under reduced pressure at 50 to 60°C to prepare a clear paste with a relative density of 1.04 to 1.10 measured at 55 to 60°C.

[0018] (2) Add water to the other medicinal materials except Panax notoginseng and decoct twice. Add 10 to 12 times the weight of water for the first decoction and decoct for 2 to 3 hours. Add 8 to 10 times the weight of water for the second decoction and decoct for 1 to 2 hours. Combine the two filtrates and concentrate under reduced pressure at 50 to 60°C to obtain a clear extract with a relative density of 1.04 to 1.12 (measured at 55°C to 60°C).

[0019] (3) Mix the clear paste obtained in step (2) with the two clear pastes obtained in step (1), and then spray-dry the supernatant to obtain the Chinese medicine composition for treating hematuria in chronic nephritis.

[0020] The beneficial effects of this application include, but are not limited to:

[0021] The traditional Chinese medicine composition for treating hematuria in chronic nephritis provided by this invention takes tonifying the kidney and promoting blood circulation as the fundamental treatment method, while also strengthening the spleen and stopping bleeding. It focuses on promoting blood circulation and stopping bleeding, and has a definite curative effect. It can improve the patient's kidney function while controlling hematuria symptoms.

[0022] Specifically, this invention uses Astragalus membranaceus, Schisandra chinensis, and Panax notoginseng as the principal herbs. Astragalus membranaceus nourishes the five internal organs and can both tonify the kidneys and promote their upward movement, as well as strengthen the spleen and stop bleeding; Schisandra chinensis tonifies the kidneys and replenishes essence, promoting the mutual transformation of essence and blood, and the liver and kidneys share the same origin, with essence and blood mutually invigorating each other; Rubia cordifolia is bitter and cold in nature, and has the effects of cooling the blood, removing blood stasis, stopping bleeding, and regulating menstruation; Panax notoginseng is a holy medicine for removing blood stasis and stopping bleeding, and is sweet, warm, and slightly bitter. It enters the blood and can also replenish blood and generate new blood. It has the characteristics of stopping bleeding without leaving blood stasis and removing blood stasis without harming the body's vital energy, and is especially suitable for those with bleeding and blood stasis.

[0023] This invention uses five herbs as assistant herbs: Rosa laevigata pulp, Euryale ferox seed, Ligustrum lucidum (processed with wine), Eclipta prostrata, and Agrimonia pilosa. Rosa laevigata pulp and Euryale ferox seed tonify the spleen and kidneys, and promote qi circulation and astringe essence; Ligustrum lucidum (processed with wine) and Eclipta prostrata nourish the liver and kidneys, replenish blood and essence, and also nourish yin and stop bleeding; Agrimonia pilosa is bitter and astringent, replenishes blood and stops bleeding; the five herbs combined can assist the principal herb in tonifying the kidneys and consolidating essence, cooling blood and stopping bleeding.

[0024] This invention uses madder root, calcined oyster shell, and cimicifuga rhizome as adjuvant herbs. Madder root, also known as "blood-seeing sorrow," was first mentioned in the *Shennong Bencao Jing* (Shennong's Classic of Materia Medica). It is a key herb for removing blood stasis, stopping bleeding, and regulating menstruation. It specifically enters the liver meridian, both stopping bleeding and regulating menstruation. The *Gu Chong Tang* (Strengthening the Chong Meridian Decoction) in *Yixue Zhongzhong Canxi Lu* (Records of Integrating Chinese and Western Medicine) uses madder root with astragalus and other herbs to treat bleeding, with significant efficacy. This formula uses this herb with astragalus and schisandra, along with notoginseng and agrimony, to tonify the kidneys, strengthen the spleen, stop bleeding, and also has phlegm-resolving properties, making it a suitable adjuvant. Calcined oyster shell has astringent and consolidating properties, and can also soften and disperse nodules. It has an auxiliary effect on various types of bleeding caused by kidney and spleen deficiency. From a microscopic perspective, the softening and dispersing properties of calcined oyster shell also have a certain effect on glomerular sclerosis and interstitial fibrosis. Cimicifuga rhizome raises yang qi, and its astringent, hemostatic, and lifting properties are used together to treat hematuria in chronic kidney disease.

[0025] In summary, the traditional Chinese medicine composition for treating hematuria in chronic nephritis provided by this invention is well-matched and refined. It can not only promote blood circulation, remove blood stasis, cool blood and stop bleeding to treat the symptoms, but also tonify the spleen and strengthen the kidneys to treat the root cause. It is an effective prescription for treating hematuria in chronic nephritis.

[0026] Pharmacological experiments have shown that the traditional Chinese medicine composition for treating hematuria in chronic nephritis provided by this invention can protect kidney function by reducing serum creatinine, blood urea nitrogen, and urinary protein levels in rats with hematuria due to nephritis; it can also promote blood circulation, remove blood stasis, and stop bleeding by reducing the number of urinary red blood cells and whole blood viscosity, significantly improving hematuria symptoms in rats, and the symptoms stabilize after discontinuation of the drug without rebound. Furthermore, clinical trials have shown that the traditional Chinese medicine composition provided by this invention has a significant therapeutic effect on hematuria in nephritis of the spleen and kidney qi deficiency with blood stasis type. Detailed Implementation

[0027] The present invention will be further described in detail below. However, it should be noted that the following specific embodiments are merely exemplary examples of the invention, and the scope of protection of the invention is not limited thereto. The scope of protection of the invention is defined only by the claims. It will be apparent to those skilled in the art that various other modifications and substitutions can be made to the embodiments of the invention within the scope of protection defined by the claims, and the same technical effects can still be achieved, thus achieving the ultimate technical objective of the invention.

[0028] Description of the medicinal materials used in this invention application:

[0029] Astragalus: The dried root of *Astragalus mongholicus* or *Astragalus membranaceus*, both belonging to the legume family. It has a sweet taste and slightly warm properties. It enters the lung and spleen meridians. Its functions include tonifying qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, generating fluids and nourishing blood, promoting circulation and relieving pain, promoting pus drainage and detoxification, and astringing sores and promoting tissue regeneration.

[0030] Wine-processed privet fruit: The dried, ripe fruit of the privet plant (Oleaceae family), stewed in wine or steamed in wine until the wine is absorbed or thoroughly steamed. Sweet, bitter, and cool in nature. It enters the liver and kidney meridians. It nourishes the liver and kidneys, improves eyesight, and darkens hair.

[0031] Eclipta prostrata: The dried aerial parts of Eclipta prostrata, a plant in the Asteraceae family. Sweet, sour, and cold in nature. It enters the kidney and liver meridians. It nourishes the liver and kidneys, cools the blood, and stops bleeding.

[0032] Panax notoginseng: The dried root and rhizome of Panax notoginseng, a plant in the Araliaceae family. Sweet and slightly bitter, warm in nature. It enters the liver and stomach meridians. It disperses blood stasis, stops bleeding, reduces swelling, and relieves pain.

[0033] Cimicifuga rhizome: The dried rhizome of Cimicifuga foetida, Cimicifuga dahurica, or Cimicifuga foetida, all belonging to the Ranunculaceae family. It is pungent, slightly sweet, and slightly cold in nature. It enters the lung, spleen, stomach, and large intestine meridians. It releases exterior pathogens and promotes rash eruption, clears heat and detoxifies, and raises yang qi.

[0034] Agrimony: The dried aerial parts of Agrimony, a plant in the Rosaceae family. Bitter, astringent, and neutral in nature. It enters the Heart and Liver meridians. Its functions include astringing and hemostasis, treating malaria, stopping dysentery, detoxifying, and tonifying deficiency.

[0035] Madder root: The dried root and rhizome of *Rubia cordifolia*, a plant in the Rubiaceae family. Bitter and cold in nature. It enters the Liver meridian. Its functions include cooling the blood, removing blood stasis, stopping bleeding, and regulating menstruation.

[0036] Vinegar-processed Schisandra chinensis: The dried, ripe fruit of the Schisandra chinensis plant (Magnolia family), steamed until black using the vinegar-steaming method. Crush before use. Sour, sweet, and warm in nature. Enters the lung, heart, and kidney meridians. Astringent and consolidating, it replenishes qi and generates fluids, tonifies the kidneys and calms the mind.

[0037] Rosa laevigata fruit pulp: The dried, mature fruit of the Rosa laevigata plant (Rosa laevigata var. laevigata). The fruit is slightly soaked until fully hydrated, then longitudinally cut in half, the hairs and seeds removed, and dried. It is sour, sweet, and astringent, and neutral in nature. It enters the kidney, bladder, and large intestine meridians. It strengthens essence and reduces urination, stops uterine bleeding and leukorrhea, and astringes the intestines to stop diarrhea.

[0038] Euryale ferox seeds: the dried, mature seeds of the Euryale ferox plant (family Nymphaeaceae). Sweet and astringent, neutral in nature. Enters the spleen and kidney meridians. Benefits the kidneys and strengthens essence, tonifies the spleen and stops diarrhea, eliminates dampness and stops leukorrhea.

[0039] Calcined oyster shell: The shell of the Pacific oyster, Dalian Bay oyster, or Lithops lizardii, which are oysters of the Ostreidae family, is washed, dried, crushed, and calcined until brittle. Calcined oyster shell has astringent and anti-acid properties, and can neutralize acid and relieve pain.

[0040] Example 1:

[0041] The traditional Chinese medicine composition for treating hematuria in chronic nephritis provided in Example 1 is prepared from the following raw materials:

[0042] Astragalus membranaceus 20 parts, Ligustrum lucidum (processed with wine) 12 parts, Eclipta prostrata 12 parts, Panax notoginseng 12 parts, Cimicifuga foetida 3 parts, Agrimonia pilosa 20 parts, Rubia cordifolia 20 parts, Schisandra chinensis (processed with vinegar) 2 parts, Rosa laevigata (processed with vinegar) 6 parts, Euryale ferox 6 parts, Ostrea gigas (calcined) 6 parts.

[0043] The preparation method of the traditional Chinese medicine composition for treating hematuria in chronic nephritis provided in Example 1 is as follows:

[0044] Panax notoginseng is pulverized into a fine powder of 80-100 mesh and prepared as Panax notoginseng powder for later use. The remaining raw materials are heated to boiling with 15 times their weight of water and decocted for 2 hours. After filtration, the residue is decocted with 12 times their weight of water for 1 hour and filtered again. The filtrates are combined and concentrated under reduced pressure to a clear extract with a relative density of 1.04-1.10 (measured at 55℃-60℃). The extract is then spray-dried to obtain spray-dried powder. The spray-dried powder is mixed evenly with Panax notoginseng powder, granulated by dry method, and packaged.

[0045] Example 2:

[0046] The raw materials of the traditional Chinese medicine composition provided in Example 2 are the same as those in Example 1, and the preparation method is as follows:

[0047] Panax notoginseng is crushed into coarse powder, soaked in 6 times its weight of 70% ethanol for 24 hours, and percolated at a flow rate of 5-7 ml / min per kilogram of medicinal material. The percolate is collected. The percolate is concentrated under reduced pressure at 50-60℃ to remove the ethanol, filtered, and the filtrate is reserved. The residue of the Panax notoginseng powder is soaked in 8 times its weight of water at 40-50℃ for 12 hours, filtered, and the filtrate is concentrated under reduced pressure at 50-60℃ to a relative density of 1.04-1.10 (measured at 55-60℃) and reserved.

[0048] The remaining raw materials were boiled twice with water. The first time, 12 times the weight of water was added and boiled for 2 hours. The second time, 10 times the weight of water was added and boiled for 1 hour. The two filtrates were combined and concentrated under reduced pressure at 50-60℃ to a clear extract with a relative density of 1.04-1.12 (measured at 55-60℃). The two clear extracts mentioned above were added, mixed well, and the supernatant was spray-dried, dry-granulated, and packaged.

[0049] Example 3:

[0050] The traditional Chinese medicine composition for treating hematuria in chronic nephritis provided in Example 3 is prepared from the following raw materials:

[0051] Astragalus membranaceus 180g, Ligustrum lucidum (processed with wine) 140g, Eclipta prostrata 100g, Panax notoginseng 100g, Cimicifuga foetida 40g, Agrimonia pilosa 180g, Rubia cordifolia 220g, Schisandra chinensis (processed with vinegar) 30g, Rosa laevigata (processed with vinegar) 70g, Euryale ferox 50g, Calcined oyster shell 500g.

[0052] The preparation method of the traditional Chinese medicine composition provided in Example 3 is the same as that in Example 1.

[0053] Example 4:

[0054] The traditional Chinese medicine composition for treating hematuria in chronic nephritis provided in Example 4 is prepared from the following raw materials:

[0055] Astragalus membranaceus 220g, Ligustrum lucidum (processed with wine) 100g, Eclipta prostrata 140g, Panax notoginseng 140g, Cimicifuga foetida 20g, Agrimonia pilosa 220g, Rubia cordifolia 180g, Schisandra chinensis (processed with vinegar) 10g, Rosa laevigata (processed with vinegar) 50g, Euryale ferox 70g, Ostrea gigas (calcined) 70g.

[0056] The preparation method of the traditional Chinese medicine composition provided in Example 4 is the same as that in Example 2.

[0057] Comparative Example 1:

[0058] The traditional Chinese medicine composition provided in Comparative Example 1 was prepared from the following raw materials:

[0059] Sample 1: Astragalus membranaceus 200g, Ligustrum lucidum (processed with wine) 12 parts, Eclipta prostrata 12 parts, Ligusticum chuanxiong 12 parts, Cimicifuga foetida 3 parts, Agrimonia pilosa 20 parts, Rubia cordifolia 20 parts, Schisandra chinensis (processed with vinegar) 2 parts, Rosa laevigata (processed with wine) 6 parts, Euryale ferox 6 parts, Ostrea gigas (calcined) 6 parts.

[0060] Comparative Example 2:

[0061] The traditional Chinese medicine composition provided in Comparative Example 2 was prepared from the following raw materials:

[0062] Sample 2: 20 parts Astragalus membranaceus, 12 parts Ligustrum lucidum (processed with wine), 12 parts Eclipta prostrata, 12 parts Salvia miltiorrhiza, 3 parts Cimicifuga foetida, 20 parts Agrimonia pilosa, 20 parts Rubia cordifolia, 2 parts Schisandra chinensis (processed with vinegar), 6 parts Rosa laevigata, 6 parts Euryale ferox, and 6 parts Calcined Ostrea gigas.

[0063] The preparation methods of the traditional Chinese medicine compositions provided in Comparative Example 1 and Comparative Example 2 are as follows:

[0064] The volatile oil of Ligusticum chuanxiong (or Salvia miltiorrhiza in Comparative Example 2) was extracted by steam distillation and set aside. The aqueous solution was collected separately. The residue and other medicinal materials were heated to boiling with 10-15 times their weight of water and decocted for 2-3 hours. After filtration, the residue was decocted with 8-12 times their weight of water for 1-2 hours. After filtration, the filtrates and the above aqueous solution were combined and concentrated under reduced pressure to a clear extract with a relative density of 1.04-1.10 (measured at 55℃-60℃). The extract was spray-dried, granulated by dry method, sprayed with the above volatile oil, mixed well, and packaged.

[0065] Comparative Example 3:

[0066] The traditional Chinese medicine composition provided in Comparative Example 3 was prepared from the following raw materials:

[0067] Sample 3: 20 parts Astragalus membranaceus, 12 parts Ligustrum lucidum (processed with wine), 12 parts Eclipta prostrata, 12 parts Imperata cylindrica, 3 parts Cimicifuga foetida, 20 parts Agrimonia pilosa, 20 parts Rubia cordifolia, 2 parts Schisandra chinensis (processed with vinegar), 6 parts Rosa laevigata, 6 parts Euryale ferox, and 6 parts Calcined Ostrea gigas.

[0068] The preparation method of the traditional Chinese medicine composition provided in Ratio 3 is as follows:

[0069] All raw materials were boiled twice with water. The first time, 12 times the weight of water was added and the decoction was carried out for 2 hours. The second time, 10 times the weight of water was added and the decoction was carried out for 1 hour. The two filtrates were combined and concentrated under reduced pressure at 50-60℃ to a clear extract with a relative density of 1.04-1.12 (measured at 55-60℃). After mixing, the supernatant was spray-dried, dry-granulated, and packaged.

[0070] In order to verify the therapeutic effect of the traditional Chinese medicine composition for treating hematuria in chronic nephritis provided by the invention, the applicant of this invention conducted the following experiments.

[0071] 1. Animal experiments:

[0072] 1.1 Materials:

[0073] Bovine serum albumin (BSA, Sigma, batch number 20180511); carbon tetrachloride (CCl4, Sigma, batch number: 20180324); lipopolysaccharide (LPS, Sigma, E. coli. 0111:B4); piperazine ferulate tablets (Kangpu Pharmaceutical Co., Ltd., National Drug Approval Number H43021780).

[0074] A commercially available traditional Chinese medicine is composed of Salvia miltiorrhiza, Astragalus membranaceus, Scutellaria baicalensis, Poria cocos, Pharbitis nil, Plantago asiatica, Imperata cylindrica, Phragmites communis, Polygonatum sibiricum, Scutellaria barbata, Typha orientalis, Leonurus japonicus, Cuscuta chinensis, Rubia cordifolia, and Crataegus pinnatifida. It has the functions of promoting blood circulation, removing blood stasis, and reducing swelling, and is used to treat edema, hematuria, and proteinuria in acute and chronic nephritis caused by damp-heat accumulation.

[0075] 1.2 Experimental animals:

[0076] After 1 week of acclimatization, 12 SD rats were randomly selected as the blank control group. The remaining rats were administered BSA by gavage every other day at a dose of 400 mg / kg for 6 weeks. Simultaneously, they were subcutaneously injected with 0.5 mL castor oil + 0.10 mL CCl4 once a week for 9 weeks, and LPS was administered in combination (0.05 mg LPS was injected via the tail vein at weeks 6 and 8, respectively). The blank control group was simultaneously administered the same dose of purified water by gavage and the same dose of physiological saline by subcutaneous injection.

[0077] 1.3 Preparation of a rat model of hematuria with nephritis:

[0078] Based on the traditional Chinese medicine theories of "exertion depletes qi" and "cold congeals blood stasis", a qi deficiency and blood stasis model was prepared to aggravate the hematuria symptoms in rats. Starting from the 6th week, the rats were placed in a water tank (about 35cm deep, placed in 4℃ ice water) in batches every day. They were forced to swim continuously until exhaustion (head submerged in water for 5-10 seconds) by being poked with a wooden stick. After being taken out, they were wiped with a towel and dried, and then put back into the cage. This was done for 14 consecutive days.

[0079] All rats were placed individually in metabolic cages, fasted but allowed water, and urine was collected and the volume was recorded. Urine was collected for urinary red blood cell count and 24-hour urinary protein detection.

[0080] 1.4 Grouping and Dosing:

[0081] Rats that successfully developed the model were randomly divided into a model control group, a piperazine ferulate positive control group, a traditional Chinese medicine positive control group, a control sample 1 (Comparative Example 1), a control sample 2 (Comparative Example 2), a control sample 3 (Comparative Example 3), a sample 1 of the present invention (Example 1), and a sample 2 of the present invention (Example 2), with 12 rats in each group. The piperazine ferulate positive control group (30 mg / kg·d), the traditional Chinese medicine positive control group, and the five sample groups were administered the drug by gavage at the dose (5.355 g / kg·d, calculated based on the daily dose of medicinal slices), once daily. The blank control group and the model control group were administered the same dose of purified water by gavage for 8 consecutive weeks.

[0082] 1.5 Sample Collection:

[0083] After the gavage treatment, urine samples were collected from all rats to detect urinary red blood cells and 24-hour urinary protein. Six rats from each group were also sampled from the abdominal aorta for biochemical index testing. The remaining rats were fed normally for two weeks before urine samples were collected to observe their recovery.

[0084] 1.6 Detection Indicators:

[0085] Detection of blood rheology, serum creatinine (Scr), and blood urea nitrogen (BUN):

[0086] After anesthetizing rats with 1.5% sodium pentobarbital solution, approximately 5 mL of blood was collected from the abdominal aorta and added to an anticoagulant tube for blood rheology analysis. Approximately 2 mL of blood was centrifuged at 4000 r / min for 5 min without anticoagulation, and the supernatant was collected to detect serum creatinine and blood urea nitrogen using a fully automated biochemical analyzer.

[0087] Measurement of urine red blood cell count:

[0088] Urine red blood cell count was detected by urine sediment microscopy. Approximately 10 mL of fresh rat urine was centrifuged at 1500 r / min for 5 min, and 0.2 mL was collected for urine sediment analysis. The urine sediment was placed in a urine sediment counting chamber, and the number of red blood cells was calculated.

[0089] 24-hour urine protein test:

[0090] Urine was collected from rats over 24 hours, centrifuged at 8000 r / min for 10 min, and the supernatant was diluted with 0.9% physiological saline. Urine protein was detected using a fully automated biochemical analyzer.

[0091] 1.7 Experimental Results:

[0092] Table 1. Effects of each drug group on hemorheology in rats with nephritis ( n=6)

[0093]

[0094] Compared with the blank group, #P<0.05, ## P<0.01; compared with the model control group, * P<0.05, * P<0.01.

[0095] In this invention, samples 1 and 2 both use Panax notoginseng as a blood-activating and stasis-removing drug, while comparative sample 1 and comparative sample 2 use Ligusticum chuanxiong and Salvia miltiorrhiza as blood-activating and stasis-removing drugs, respectively. Comparative sample 3 does not contain any blood-activating drugs, and Panax notoginseng is replaced with Imperata cylindrica as a hemostatic drug, thus forming four prescriptions.

[0096] After 8 weeks of administration, compared with the blank control group, the whole blood viscosity (low shear, medium shear, and high shear) of the model control group was significantly increased (P<0.01). Compared with the model control group, the whole blood viscosity (low shear, medium shear, and high shear) of the control sample 1 group, control sample 2 group, and the present invention sample 1 and 2 groups all showed a significant decreasing trend (P<0.01), indicating that all three prescriptions have outstanding blood-activating and stasis-removing effects. The efficacy of the present invention sample 2 group was slightly better than that of the present invention sample 1 group; there was no significant difference in whole blood viscosity between the three control sample groups and the model group.

[0097] Table 2. Effects of each drug group on serum Scr and BUN in rats with nephritis.

[0098]

[0099] Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group * P<0.05, ** P<0.01.

[0100] Compared with the blank control group, the serum creatinine (Scr) and blood urea nitrogen (BUN) levels in the model control group were significantly increased (P<0.01). Compared with the model control group, the serum creatinine and blood urea nitrogen levels in samples 1 and 2 of this invention were significantly lower after treatment (P<0.01), and the effect was better than that of the positive control group and the control samples 1, 2, and 3. These results indicate that samples 1 and 2 of this invention can protect renal function by reducing serum creatinine and blood urea nitrogen levels.

[0101] Table 3. Effects of each drug group on urinary erythrocytes in rats with nephritis ( n=6)

[0102]

[0103] Table 4. Effects of each drug group on urinary protein in rats with nephritis ( n=6)

[0104]

[0105]

[0106] Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01; compared with 8 weeks after administration ☆ P<0.05.

[0107] On day 0 of drug administration, compared with the blank control group, the urinary red blood cell count and 24-hour urinary protein quantification of the model control group and each sample group were significantly increased, with statistically significant differences (P<0.01), indicating successful model establishment. After 8 weeks of drug administration, compared with the model control group, the urinary red blood cell count and 24-hour urinary protein quantification of sample groups 1 and 2 of this invention were significantly decreased (P<0.01). Compared with 8 weeks of drug administration, 2 weeks after drug withdrawal, there was no significant difference in urinary red blood cell count and 24-hour urinary protein quantification in sample groups 1 and 2 of this invention, and the therapeutic effect was more stable than that of the positive control drug. The urinary red blood cell count of rats in sample group 2 of this invention was slightly lower than that in sample group 1 of this invention after treatment. It can be seen that sample groups 1 and 2 of this invention have significant therapeutic effects on hematuria caused by nephritis, and the therapeutic effect is stable after drug withdrawal.

[0108] The three groups of comparative samples focused on hemostasis, removing the blood-activating herb Panax notoginseng and adding the hemostatic herb Imperata cylindrica. While the hemostatic effect was significant after administration, the urinary red blood cell count increased significantly after discontinuation of the medication, indicating unstable treatment efficacy. This suggests that the treatment of hematuria in chronic nephritis should not only focus on hemostasis but also consider promoting blood circulation and removing blood stasis.

[0109] Furthermore, comparative sample group 1 and comparative sample group 2 used Chuanxiong and Danshen as blood-activating and stasis-removing drugs, respectively, while sample groups 1 and 2 of this invention used Sanqi as a blood-activating and stasis-removing drug. This indicates that although Chuanxiong, Danshen, and Sanqi have similar effects, different blood-activating and stasis-removing drugs, when combined with other hemostatic drugs, can significantly affect the overall efficacy of the traditional Chinese medicine composition. In this invention, the rational combination of Sanqi with other raw materials achieves excellent therapeutic effects for hematuria in nephritis.

[0110] 2. Clinical trials:

[0111] 2.1 Source of cases:

[0112] Sixty patients who visited the outpatient department of Shandong Hongjitang Traditional Chinese Medicine Hospital from August 2021 to December 2022 were selected and randomly divided into a treatment group and a control group (30 cases in each group) according to the order of enrollment. There were 35 males and 25 females. The mean age of the treatment group was 42.3 ± 10.1 years, and the mean age of the control group was 45.7 ± 12.4 years. All selected cases met the inclusion criteria. Before treatment, the serum creatinine and blood urea nitrogen levels of all patients in both groups were within the normal range, and liver function and blood routine tests were also normal.

[0113] 2.2 Western Medicine Diagnostic Criteria:

[0114] (2) Meets the diagnostic criteria for chronic glomerulonephritis in Nephrology. Meets the criteria for hematuria in nephritis in Nephrology: ① Fresh urine sediment microscopy shows ≥3 red blood cells per high-power field, or ≥100,000 red blood cells excreted per hour, or ≥500,000 red blood cells in urine sediment over 12 hours; ② When observed with a phase microscope, the proportion of abnormal red blood cells in urine sediment exceeds 75%.

[0115] 2.3 Traditional Chinese Medicine (TCM) Syndrome Differentiation and Classification Standards:

[0116] Spleen and Kidney Qi Deficiency Syndrome

[0117] Main symptoms: lower back pain, fatigue, or edema, poor appetite, or abdominal distension.

[0118] Secondary symptoms: loose stools, frequent urination or nocturia, pale red tongue with teeth marks, thin white coating, and thready pulse.

[0119] Blood stasis syndrome

[0120] Main symptoms: Dark or dull complexion; fixed or stabbing lower back pain; dark purple tongue or petechiae and ecchymosis.

[0121] Secondary symptoms: rough skin or numbness in the limbs, weak and hesitant pulse, elevated urinary FDP levels, and elevated whole blood and plasma viscosity as detected by blood rheology tests.

[0122] 2.4 Inclusion and Exclusion Criteria:

[0123] Inclusion criteria: (1) chronic glomerulonephritis with renal hematuria as the main clinical manifestation, meeting the Western medicine diagnostic criteria for this disease (≥3 red blood cells in routine urine microscopy); (2) syndrome differentiation is spleen and kidney qi deficiency with blood stasis type; (3) aware of the condition, voluntarily participate and sign the relevant informed consent form; (4) age between 18 and 70 years old.

[0124] Exclusion criteria: (1) Patients with stage III or IV renal insufficiency or renal failure; (2) Hematuria due to chronic nephritis caused by systemic lupus erythematosus, drug-induced kidney damage, etc.; (3) Patients with serious primary diseases of the heart, brain, liver and hematopoietic system; (4) Women who are pregnant or lactating; (5) Patients with poor compliance who cannot obtain effective research data.

[0125] 2.5 Treatment methods:

[0126] Control group: In addition to routine basic treatments such as diet control, blood pressure reduction, and lipid reduction, piperazine ferulate tablets were given 150mg three times a day for 12 weeks.

[0127] Treatment group: In addition to routine basic treatment, the granules of this invention were administered twice daily, 10g each time, for a course of 12 weeks.

[0128] 2.6 Observation Indicators:

[0129] (1) Urine red blood cell count

[0130] (2) TCM syndrome scoring: The main symptoms are scored as mild, moderate and severe, with scores of 2, 4 and 6 respectively; the secondary symptoms are scored as 1, 2 and 3. The sum of the main symptoms score and the secondary symptoms score is the TCM syndrome score.

[0131] 2.7 Criteria for Judging Therapeutic Effect:

[0132] Evaluation of treatment efficacy for urinary red blood cell count:

[0133] (1) Clinical control: RBC count is normal in routine urine test or RBC count in urine sediment is normal.

[0134] (2) Significant effect: RBC reduction of ≥3 / HP or 2 "+", or RBC count reduction in urine sediment ≥40%.

[0135] (3) Effective: RBC reduction of <3 / HP or 1 "+" or RBC reduction of <40% in urine sediment RBC count examination.

[0136] (4) Ineffective: No change or increase in urine RBC count.

[0137] 2.8 Criteria for Evaluating the Therapeutic Effect of Traditional Chinese Medicine Syndromes:

[0138] (1) Clinical cure: TCM clinical symptoms and signs disappear or basically disappear, and the syndrome score is reduced by ≥95%.

[0139] (2) Significant effect: Clinical symptoms and signs in TCM are significantly improved, and the syndrome score is reduced by ≥70%.

[0140] (3) Effective: The clinical symptoms and signs of TCM patients have improved, and the syndrome score has decreased by ≥30%.

[0141] (4) Ineffective: The clinical symptoms and signs in TCM have not improved significantly, or have even worsened, and the syndrome score has decreased by less than 30%.

[0142] Note: The calculation formula (nimodipine method) is: [(pre-treatment score - post-treatment score) / pre-treatment score] × 100%.

[0143] Statistical methods: SPSS 19.0 software was used for data analysis. Quantitative data were analyzed using... The t-test was used to compare the means of the two groups, and P < 0.05 was considered statistically significant.

[0144] 2.9 Therapeutic Results:

[0145] Table 5. Evaluation of the efficacy of treatment on urinary red blood cell count before and after treatment in the two groups.

[0146]

[0147]

[0148] Table 6. Evaluation of TCM symptom scores before and after treatment in the two groups.

[0149] Group Number of examples Clinically cured Effective efficient invalid Overall effectiveness (%) Treatment group 30 3 8 15 4 86.7 control group 30 2 4 13 11 63.3

[0150] The results above show that the total effective rate of the treatment group for hematuria was higher than that of the control group, and the TCM syndrome score after treatment was significantly higher than that of the control group. This indicates that the TCM composition (treatment group) provided by the present invention has a significantly better therapeutic effect on hematuria of nephritis with spleen and kidney qi deficiency and blood stasis than the control group, and the difference is statistically significant (P<0.05).

[0151] The above specific embodiments should not be construed as limiting the scope of protection of the present invention. For those skilled in the art, any alternative improvements or modifications made to the embodiments of the present invention shall fall within the scope of protection of the present invention.

[0152] Any aspects of this invention not described in detail are well-known to those skilled in the art.

Claims

1. A traditional Chinese medicine composition for treating hematuria in chronic nephritis, characterized in that, Made from the following parts by weight of raw materials: Astragalus membranaceus 18-22 parts, Ligustrum lucidum (processed with wine) 10-14 parts, Eclipta prostrata 10-14 parts, Panax notoginseng 10-14 parts, Cimicifuga foetida 2-4 parts, Agrimonia pilosa 18-22 parts, Rubia cordifolia 18-22 parts, Schisandra chinensis (processed with vinegar) 1-3 parts, Rosa laevigata (processed with vinegar) 5-7 parts, Euryale ferox 5-7 parts, Calcined oyster shell 5-7 parts; The preparation method of the traditional Chinese medicine composition includes the following steps: S1. Grind Panax notoginseng into a fine powder of 80-100 mesh to make Panax notoginseng powder; S2. Add 10-15 times the weight of water to the remaining raw materials, heat to boiling, and continue to decoct for 2-3 hours. Filter, add 8-12 times the weight of water to the dregs, and continue to decoct for 1-2 hours. Filter, combine the two filtrates, concentrate the filtrate under reduced pressure to 55℃-60℃ to obtain a clear extract with a relative density of 1.04-1.10, spray dry to obtain spray-dried powder. S3. Spray-dried powder and Panax notoginseng powder are mixed evenly to prepare an extract of the traditional Chinese medicine composition for treating hematuria in chronic nephritis. Alternatively, the preparation method of the traditional Chinese medicine composition may include the following steps: (1) Grind Panax notoginseng into coarse powder, add 6 to 8 times its weight of 60% to 70% ethanol and soak for 24 hours. Percolate at a flow rate of 5 to 7 ml / min per kilogram of coarse powder and collect the percolate. Concentrate the percolate under reduced pressure at 50 to 60°C to remove the ethanol, filter, and obtain Panax notoginseng concentrated extract and filter residue. Add 6 to 8 times the weight of water to the filter residue and soak at 40 to 50°C for 8 to 12 hours. Filter, combine the filtrates, and concentrate under reduced pressure at 50 to 60°C to prepare a clear paste with a relative density of 1.04 to 1.10 measured at 55 to 60°C. (2) Add water to the other medicinal materials except Panax notoginseng and decoct twice. Add 10 to 12 times the weight of water for the first decoction and decoct for 2 to 3 hours. Add 8 to 10 times the weight of water for the second decoction and decoct for 1 to 2 hours. Combine the two filtrates and concentrate under reduced pressure at 50 to 60°C. Concentrate to 55°C to 60°C and measure the relative density of the extract to be 1.04 to 1.

12. (3) After mixing the clear paste obtained in step (2) with the two clear pastes obtained in step (1), take the supernatant and spray dry it to obtain the extract of the traditional Chinese medicine composition for treating hematuria in chronic nephritis.

2. The traditional Chinese medicine composition for treating hematuria in chronic nephritis according to claim 1, characterized in that, The weight proportions of each ingredient are as follows: Astragalus membranaceus 20 parts, Ligustrum lucidum 12 parts, Eclipta prostrata 12 parts, Panax notoginseng 12 parts, Cimicifuga foetida 3 parts, Agrimonia pilosa 20 parts, Rubia cordifolia 20 parts, Schisandra chinensis 2 parts, Rosa laevigata 6 parts, Euryale ferox 6 parts, and Ostrea gigas 6 parts.

3. The traditional Chinese medicine composition for treating hematuria in chronic nephritis according to claim 1, characterized in that, An oral preparation is prepared by adding an extract of the traditional Chinese medicine composition according to claim 1 or 2 to a pharmaceutically acceptable carrier, wherein the oral preparation is an oral liquid, granules, tablets, capsules or pills.

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