Traditional Chinese medicine composition and medicine for preventing and treating diabetic nephropathy as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicinal materials, in particular to a traditional Chinese medicinal composition for preventing and treating diabetic nephropathy, a medicine and a preparation method and application thereof. In the traditional Chinese medicine composition provided by the invention, the astragalus membranaceus is used as a monarch drug, the radix ophiopogonis and the desmodium styracifolium are used as ministerial drugs, the saffron crocus, the gentiana scabra bunge, the rheum officinale and the cowherb seed are used as adjuvant drugs, and the liquorice is used as a conductant drug. According to the traditional Chinese medicine composition provided by the invention, through reasonable compatibility of monarch, minister, assistant and guide, multiple effects of tonifying qi and strengthening superficies, nourishing yin and moistening dryness, promoting blood circulation to remove blood stasis, clearing heat and promoting diuresis and the like are comprehensively exerted, so that the aim of treating diabetic nephropathy is fulfilled. Meanwhile, the result of the specific embodiment of the invention shows that the traditional Chinese medicine composition or medicine provided by the invention can effectively reduce urine protein and uric acid of the DKD patient and protect the renal function, the effect of the traditional Chinese medicine composition or medicine is equivalent to that of a positive control group, and the cure rate of the DKD patient can be remarkably improved.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition, a drug, a preparation method and an application thereof for preventing and treating diabetic kidney disease. Background Art

[0002] Diabetic Kidney Disease (DKD) is one of the common and serious complications of diabetic patients, and is also the main cause of End-Stage Renal Disease (ESRD), and is also one of the reasons for the significant increase in the incidence and mortality of cardiovascular diseases in diabetic patients. In recent years, with the increase in the incidence of diabetes, DKD has become the main cause of chronic kidney disease in China, bringing a heavy burden to the medical and health system.

[0003] Research shows that the pathological mechanism of diabetic kidney disease involves multiple factors, including metabolic disorders caused by hyperglycemia, inflammatory responses, oxidative stress, changes in renal hemodynamics, etc. These factors act together to cause pathological changes such as thickening of the glomerular basement membrane, glomerulosclerosis, and interstitial fibrosis. At present, early diagnosis and monitoring of diabetic kidney disease are crucial for preventing the progression of the disease. Traditional diagnostic methods rely on the detection of urinary proteins (such as urinary albumin), but in recent years, new biomarkers (such as NGAL, KIM-1, cystatin C) are being studied and applied to detect kidney injury earlier. At the same time, there are also imaging examination methods, such as ultrasound, magnetic resonance imaging (MRI), etc., which are also used to evaluate the changes in the structure and function of the kidneys.

[0004] The current strategies for treating DKD in Western medicine mainly focus on four aspects: controlling blood sugar, controlling blood pressure, inhibiting the renin-angiotensin system, and reducing cardiovascular risk. The existing therapies are very limited in preventing the progression of DKD. The exploration and optimization of DKD treatment regimens have always been a major problem in the field of nephrology. In the field of traditional Chinese medicine, medical experts mostly believe that it is closely related to "urinary turbidity", "kidney wasting", "edema", "guan ge" and so on secondary to long-term consumption of sweet drinks. It is due to various factors that cause the abnormal qi transformation function of the human body, and the essence of water and grain cannot be normally steamed and distributed, thus affecting the physiological functions of the lungs, spleen, kidneys, etc., belonging to the syndrome of deficiency in origin and excess in superficiality. The treatment of DKD with traditional Chinese medicine mostly focuses on syndromes, with the characteristics of "holistic concept" and "syndrome differentiation and treatment", mainly based on staging and syndrome differentiation and typing.

[0005] However, although significant progress has been made in the research on diabetic kidney disease in the medical field in terms of pathological mechanisms, diagnostic markers, treatment strategies, etc., there are still many problems to be solved. For example, long-term use of Western medicine has great toxic and side effects on the human body. Therefore, finding a traditional Chinese medicine composition that can effectively prevent and treat DKD, delay the progression of DKD and has high safety has important clinical value and social significance. Summary of the Invention

[0006] The purpose of the present invention is to provide a traditional Chinese medicine composition, a drug and its preparation method and application for preventing and treating diabetic kidney disease, so as to solve the problems existing in the above-mentioned prior art.

[0007] To achieve the above purpose, the present invention provides the following solutions:

[0008] The present invention provides a traditional Chinese medicine composition for preventing and treating diabetic kidney disease, which includes the following components by weight: 15-20 parts of Astragalus membranaceus, 4-7 parts of Crocus sativus, 5-10 parts of Rheum palmatum, 10-15 parts of Vaccaria segetalis, 5-10 parts of Desmodium styracifolium, 4-8 parts of Gentiana rhodantha, 3-5 parts of Ophiopogon japonicus and 3-5 parts of Glycyrrhiza uralensis.

[0009] Preferably, by weight, the traditional Chinese medicine composition includes the following components: 18 parts of Astragalus membranaceus, 5 parts of Crocus sativus, 8 parts of Rheum palmatum, 13 parts of Vaccaria segetalis, 12 parts of Desmodium styracifolium, 5 parts of Gentiana rhodantha, 4 parts of Ophiopogon japonicus and 3 parts of Glycyrrhiza uralensis.

[0010] The present invention provides an application of the above traditional Chinese medicine composition in the preparation of a drug for preventing and treating diabetic kidney disease.

[0011] The present invention provides a drug for preventing and treating diabetic kidney disease, and the preparation raw materials of the drug include the above traditional Chinese medicine composition.

[0012] Preferably, the drug further includes pharmaceutically acceptable excipients.

[0013] Preferably, the dosage form of the drug is decoction, pill, capsule, tablet, powder or granule.

[0014] The present invention provides a preparation method of the above drug, which includes the following steps:

[0015] Performing water extraction on the mixture of Astragalus membranaceus, Crocus sativus, Rheum palmatum, Vaccaria segetalis, Desmodium styracifolium, Gentiana rhodantha, Ophiopogon japonicus and Glycyrrhiza uralensis to obtain a water extract and a water extract residue;

[0016] Performing enzymatic hydrolysis on the water extract residue to obtain an enzymatic hydrolysate;

[0017] Mixing the water extract and the enzymatic hydrolysate and then concentrating to obtain the drug.

[0018] Preferably, when performing the water extraction, the mass ratio of the mixture to water is 1:12; the temperature of the water extraction is 85 °C and the time is 3 h.

[0019] Preferably, the enzyme preparation used for the enzymatic hydrolysis is a trypsin solution.

[0020] Preferably, when performing the enzymatic hydrolysis, the dosage of the enzyme preparation is 0.8% of the mass of the water extract; the temperature of the enzymatic hydrolysis is 45 °C and the time is 30 min.

[0021] The present invention discloses the following technical effects:

[0022] In the traditional Chinese medicine composition provided by the present invention, Astragalus membranaceus is used as the monarch drug. Astragalus membranaceus has the functions of replenishing qi and consolidating the exterior, promoting diuresis and reducing swelling, and is one of the core drugs for treating diabetic nephropathy. It can help improve kidney function, enhance the body's immunity, and promote the correction of abnormal protein metabolism. Ophiopogon japonicus and Desmodium styracifolium are used as ministerial drugs. Ophiopogon japonicus mainly plays the role of nourishing yin and moistening dryness, and can relieve symptoms such as dry mouth and excessive drinking caused by yin deficiency in diabetic nephropathy patients; Desmodium styracifolium has the effects of clearing heat and promoting diuresis, and removing calculi by diuresis, and can assist in improving the urinary tract symptoms of diabetic nephropathy patients. Crocus sativus, Gentiana rhodantha, Rheum palmatum, and Vaccaria segetalis are used as adjuvant drugs. Crocus sativus promotes blood circulation and removes stasis, improves microcirculation, and reduces kidney damage. Gentiana rhodantha clears heat and detoxifies, and further enhances the effect of promoting blood circulation and removing stasis. Rheum palmatum purges downward to relieve constipation, removes blood stasis and dredges menstruation, helps to remove toxins and blood stasis in the body, and reduces the burden on the kidneys. Vaccaria segetalis promotes menstruation and lactation, and promotes diuresis and relieves stranguria, and can be used to improve the edema and oliguria symptoms of diabetic nephropathy patients. Licorice is used as the guiding drug, which has the functions of coordinating the actions of various drugs and relieving spasm and pain, and at the same time can nourish the spleen and stomach and enhance the overall therapeutic effect. In summary, through the reasonable compatibility of the monarch, ministerial, adjuvant, and guiding drugs, the traditional Chinese medicine composition comprehensively exerts multiple effects such as replenishing qi and consolidating the exterior, nourishing yin and moistening dryness, promoting blood circulation and removing stasis, and clearing heat and promoting diuresis, so as to achieve the purpose of treating diabetic nephropathy. The results of the specific embodiments of the present invention show that taking the traditional Chinese medicine composition or drug provided by the present invention can effectively reduce the urine protein and uric acid of DKD patients, protect kidney function, and its effect is equivalent to that of the positive control group, and can also significantly improve the cure rate of DKD patients. Detailed implementation manners

[0023] The various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics, and implementation schemes of the present invention.

[0024] It should be understood that the terms used in the present invention are only for describing specific embodiments and are not intended to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0025] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the said documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0026] Without departing from the scope or spirit of the present invention, various improvements and variations can be made to the specific embodiments of the present invention specification, which are obvious to those skilled in the art. Other embodiments obtained from the specification of the present invention are obvious to those skilled in the art. The specification and examples of the present invention are merely exemplary.

[0027] Regarding the use of "comprising", "including", "having", "containing", etc. herein, they are all open-ended terms, meaning including but not limited to.

[0028] Example 1

[0029] A traditional Chinese medicine composition for preventing and treating diabetic nephropathy, by weight, consists of the following components: 18 parts of Astragalus membranaceus, 5 parts of Crocus sativus, 8 parts of Rheum palmatum, 13 parts of Vaccaria segetalis, 12 parts of Desmodium styracifolium, 5 parts of Gentiana rhodantha, 4 parts of Ophiopogon japonicus, and 3 parts of Glycyrrhiza uralensis.

[0030] A drug for preventing and treating diabetic nephropathy, the raw material for its preparation is the traditional Chinese medicine composition as described above, and the preparation method of this drug is as follows:

[0031] Crush Astragalus membranaceus, Crocus sativus, Rheum palmatum, Vaccaria segetalis, Desmodium styracifolium, Gentiana rhodantha, Ophiopogon japonicus, and Glycyrrhiza uralensis into powders with a particle size of 100 nm respectively, and mix them to obtain traditional Chinese medicine powders;

[0032] Mix the traditional Chinese medicine powders with water in a mass ratio of 1:12, and extract with water at 85 °C for 3 h to obtain an aqueous extract and an aqueous extract residue;

[0033] The obtained aqueous extract was enzymatically hydrolyzed to obtain an enzymatic hydrolysate. The enzyme preparation was a trypsin solution at 1000 U / mL, and the dosage of the enzyme preparation was 0.8% of the mass of the extract. The temperature of enzymatic hydrolysis was 45 °C and the time was 30 min.

[0034] After mixing the obtained aqueous extract and the obtained enzymatic hydrolysate, it was concentrated to an extract with a relative density of 1.25 to obtain the drug.

[0035] Example 2

[0036] A traditional Chinese medicine composition for preventing and treating diabetic nephropathy, calculated by weight, consists of the following components: 15 parts of Astragalus membranaceus, 7 parts of Crocus sativus, 5 parts of Rheum palmatum, 15 parts of Vaccaria segetalis, 5 parts of Desmodium styracifolium, 4 parts of Gentiana rhodantha, 5 parts of Ophiopogon japonicus, and 3 parts of Glycyrrhiza uralensis.

[0037] A drug for preventing and treating diabetic nephropathy, the raw materials for its preparation being the traditional Chinese medicine composition as described above, and the preparation method of this drug being the same as that of Example 1.

[0038] Example 3

[0039] A traditional Chinese medicine composition for preventing and treating diabetic nephropathy, calculated by weight, consists of the following components: 20 parts of Astragalus membranaceus, 4 parts of Crocus sativus, 10 parts of Rheum palmatum, 10 parts of Vaccaria segetalis, 10 parts of Desmodium styracifolium, 8 parts of Gentiana rhodantha, 3 parts of Ophiopogon japonicus, and 5 parts of Glycyrrhiza uralensis.

[0040] A drug for preventing and treating diabetic nephropathy, the raw materials for its preparation being the traditional Chinese medicine composition as described above, and the preparation method of this drug being the same as that of Example 1.

[0041] Control Example 1

[0042] A traditional Chinese medicine composition for preventing and treating diabetic nephropathy, calculated by weight, consists of the following components: 15 parts of Astragalus membranaceus, 10 parts of Rheum palmatum, and 10 parts of Crocus sativus.

[0043] A drug for preventing and treating diabetic nephropathy, the raw materials for its preparation being the traditional Chinese medicine composition as described above, and the preparation method of this drug is as follows:

[0044] After mixing Astragalus membranaceus and Rheum palmatum, they were mixed with water in a mass ratio of 1:16 times, decocted and extracted for 2 h, and the number of times of decoction and extraction was 4 times. Then, it was filtered and concentrated to an extract with a relative density of 1.25 to obtain an extract.

[0045] The obtained extract was dried at 60 °C to a constant mass, taken out, pulverized, and the pulverized Crocus sativus was added and mixed evenly to obtain the drug.

[0046] Control Example 2

[0047] The difference from Example 1 is only that: Astragalus membranaceus was replaced with Polygonatum sibiricum.

[0048] Comparative Example 3

[0049] The difference from Example 1 is only that: in the process of preparing the drug for preventing and treating diabetic nephropathy, the concentration step is omitted.

[0050] Comparative Example 4

[0051] The difference from Example 1 is only that: the trypsin solution is replaced with a cellulase solution.

[0052] Experimental Example 1 Toxicity Experiment

[0053] Test animals: 70 Kunming mice, weighing about 50 g, half male and half female. 10 mice were treated with Examples 1-3 and Comparative Examples 1-4 respectively, and gavaged at 2 mL / mouse / day. At the same time, distilled water with the same volume was used as the control group by gavage. No obvious toxic and side reactions occurred in the animals before and after administration. After continuous observation for 14 days, the animals had no death and no abnormal manifestations. The test results showed that: the drugs of Examples 1-3 and Comparative Examples 1-4 had no obvious toxicity to the experimental animals, indicating that the drugs of Examples 1-3 and Comparative Examples 1-4 were safe for clinical application.

[0054] Experimental Example 2 Clinical Experiment

[0055] 1.1 Research Subjects

[0056] 160 DKD patients who visited the outpatient department or were hospitalized in Lanzhou University Affiliated Hospital from January 2017 to January 2020 were selected. The patients were divided into 8 groups by random number method: treatment group (Examples 1-3 and Comparative Examples 1-4, a total of seven groups), positive control group (irbesartan), with 20 patients in each group. There were no obvious differences among the three groups in terms of gender, age, disease course, blood pressure, serum uric acid, and creatinine composition.

[0057] Inclusion criteria: (1) Aged 18-65 years, gender not limited; (2) Patients diagnosed with stage II-III diabetic nephropathy; (3) Blood pressure effectively controlled; (4) Voluntary participants.

[0058] Exclusion criteria: (1) Patients with primary or secondary chronic kidney diseases; (2) Those who did not take ACEI / ARB and Chinese herbal medicines containing rhubarb, astragalus membranaceus, saffron, semen vaccariae, desmodium styracifolium, gentianopsis barbata, ophiopogon japonicus, and licorice within 1 month before entering the study; (3) Those with mental diseases or those who were unwilling to take Chinese herbal medicines; (4) Those with recent acute infections; (5) Severe digestive tract diseases, such as active ulcers, chronic diarrhea, and post-gastrointestinal surgery; (6) Those with diseases of the heart, brain, liver, and hematopoietic system; (7) Those with primary hypertension; (8) Those with ketoacidosis and lactic acidosis; (9) Pregnant or lactating women.

[0059] Efficacy evaluation criteria:

[0060] (1) Basic cure: Symptoms and signs disappear, urine routine examination is normal for 3 times, and the indicators of urinary microprotein quantification, blood lipid, plasma protein, urea nitrogen, and creatinine are all normal.

[0061] (2) Marked effect: Symptoms and signs disappear, urine protein qualitative is + - ++, 24-hour urinary protein quantification is reduced by more than 1 / 2 compared with that before treatment, blood lipid is significantly improved, and the indicators of urea nitrogen and creatinine are close to normal.

[0062] (3) Effective: Clinical symptoms are somewhat alleviated, urine protein qualitative is ++ - ++++, blood lipid indicators decline, and urea nitrogen and creatinine improve somewhat.

[0063] (4) Ineffective: Symptoms, signs, and relevant laboratory tests show no obvious change or even aggravation.

[0064] This example was reviewed and approved by the hospital ethics committee, and all research subjects signed informed consent forms.

[0065] 1.2 Methods

[0066] 1.2.1 Treatment method

[0067] The positive control group took irbesartan 150 - 300 mg per day. The treatment group took the drugs in Examples 1 - 3 and Comparative Examples 1 - 4, 200 mL, twice a day. Other treatments included blood glucose control, and the blood pressure control target was 130 / 80 mmHg. If the blood pressure did not reach the standard, CCB drugs were added.

[0068] 1.2.2 Observation indicators

[0069] All patients had 8 mL of fasting blood collected before entering the study and after the study ended for the detection of serum creatinine (Scr) and uric acid (UA). Urine specimens were collected for urine routine and 24-hour urinary protein quantification (24-hour urinary protein excretion, 24h-UPE) detection. At the same time, all patients recorded their weight, height, and blood pressure daily.

[0070] 1.2.3 Statistical methods

[0071] Measurement data were expressed as x ± s, and count data were expressed as percentages. SPSS 19.0 software was used for univariate analysis of the data. Measurement data were analyzed by t-test, and count data were analyzed by χ 2 test. P < 0.05 indicated statistical significance.

[0072] 2 Results

[0073] 2.1 General clinical data of different patients

[0074] The inventors compared the baseline clinical data of two groups of patients. There were no significant differences in age, gender, blood pressure, disease stage, 24-hour urinary protein excretion, cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, and uric acid between the three groups of patients (P > 0.05). See Table 1 for details.

[0075] Table 1 Baseline clinical data of patients in different groups (n = 20)

[0076]

[0077] 2.2 Effects of the administered drugs on urinary protein and renal function in DKD patients

[0078] The effects of the administered drugs on urinary protein and renal function in DKD patients are shown in Table 2.

[0079] Table 2 Urinary protein and renal function (n = 20)

[0080]

[0081] The results showed that after 6 months of treatment, the drugs prepared in Examples 1 - 3 could reduce the urinary protein and uric acid in DKD patients and protect renal function, and the effects were comparable to those of the positive control group.

[0082] 2.3 Comparison of the comprehensive curative effects on DKD patients before and after taking the drugs

[0083] The comprehensive curative effects on DKD patients before and after taking the drugs are shown in Table 3.

[0084] Table 3 Comparison of the comprehensive curative effects on DKD patients before and after taking the drugs (n = 20)

[0085] Group Basically cured (cases) Markedly effective (cases) Effective (cases) Ineffective (cases) Positive control group 10 3 4 3 Example 1 8 8 3 1 Example 2 9 5 4 2 Example 3 10 4 4 2 Comparative example 1 5 2 5 8 Comparative example 2 7 1 5 7 Comparative example 3 8 3 4 5 Comparative example 4 7 2 3 8

[0086] The results showed that after 6 months of treatment, the drugs prepared in Examples 1 - 3 could significantly improve the cure rate of DKD patients.

[0087] The above-described embodiments are only descriptions of the preferred embodiments of the present invention and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. A Chinese medicine composition for preventing and treating diabetic nephropathy, characterized in that: The invention comprises the following components by weight: 15-20 parts of astragalus, 4-7 parts of saffron, 5-10 parts of rhubarb, 10-15 parts of fenugreek, 5-10 parts of safflower, 4-8 parts of gentiana scabra, 3-5 parts of ophiopogon and 3-5 parts of liquorice.

2. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition comprises the following components by weight: 18 parts of astragalus, 5 parts of saffron, 8 parts of rhubarb, 13 parts of fenugreek, 12 parts of safflower, 5 parts of gentiana scabra, 4 parts of ophiopogon and 3 parts of liquorice.

3. Use of the Chinese medicine composition as claimed in claim 1 or 2 in the preparation of a medicament for preventing and treating diabetic nephropathy.

4. A drug for preventing and treating diabetic nephropathy, characterized in that: The raw materials for preparing the medicine include the traditional Chinese medicine composition according to claim 1 or 2.

5. The drug according to claim 4, characterized in that The medicine also includes pharmaceutically acceptable auxiliary materials.

6. The drug according to claim 5, characterized in that The dosage form of the medicine is decoction, pill, capsule, tablet, powder or granule.

7. The method for preparing the drug according to claim 4, characterized in that: The following steps are involved: Extracting the mixture of the astragalus, saffron, rhubarb, vaccaria, lysimachia truncatum, gentiana scabra, ophiopogon japonicus and liquorice with water to obtain a water extract and a water extract; Performing enzymatic hydrolysis on the water extract to obtain an enzymatic hydrolyzate; The water extract and the enzymatic hydrolyzate are mixed and then concentrated to obtain the drug.

8. The preparation method according to claim 7, characterized in that: When performing the water extraction, the mass ratio of the mixture to water is 1:12; the temperature of the water extraction is 85° C., and the time is 3 hours.

9. The preparation method according to claim 7, characterized in that: The enzyme preparation used in the enzymolysis is trypsin solution.

10. The preparation method according to claim 9, characterized in that: When performing the enzymolysis, the dosage of the enzyme preparation is 0.8% of the mass of the water extract; the temperature of the enzymolysis is 45° C., and the time is 30 minutes.

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