CN112933201A - Traditional Chinese medicine composition and traditional Chinese medicine preparation for treating diabetic nephropathy and preparation method thereof - Google Patents
Traditional Chinese medicine composition and traditional Chinese medicine preparation for treating diabetic nephropathy and preparation method thereof Download PDFInfo
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Abstract
The invention provides a traditional Chinese medicine composition for treating diabetic nephropathy, which comprises 5-30 parts of raw astragalus, 5-20 parts of codonopsis pilosula, 5-20 parts of prepared cornus officinalis, 5-20 parts of herba lycopi, 5-20 parts of rhizoma alismatis, 5-30 parts of ternate buttercup root, 10-40 parts of rhizoma smilacis glabrae, 5-20 parts of kadsura pepper stem, 5-20 parts of dioscorea nipponica, 5-20 parts of trichosanthes root, 5-20 parts of angelica and 5-20 parts of curcuma zedoary. The invention also provides a traditional Chinese medicine preparation prepared from the traditional Chinese medicine composition and a preparation method thereof. The traditional Chinese medicine composition has complete monarch, minister, assistant and guide functions, precise compatibility and mutual assistance, has the functions of reinforcing the kidney, dispelling wind, discharging turbidity and dredging collaterals, has obvious effect on improving the clinical symptoms of diabetic nephropathy, can reduce the blood creatinine, urea nitrogen and urine protein of patients with diabetic nephropathy, has good kidney protection effect and has good application prospect.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a traditional Chinese medicine composition for treating diabetic nephropathy, a traditional Chinese medicine preparation and a preparation method thereof.
Background
Diabetic Nephropathy (DN) is a common chronic complication of type 1 and type 2 diabetes mellitus, is clinically mainly manifested by chronic hyperglycemia, proteinuria and progressive renal function impairment, and has a high disability rate. The pathogenesis of diabetic nephropathy is not clarified, and genetic factors, hemodynamic changes, inflammatory cell infiltration, glucose metabolism disorders and hypoxia are considered to cause diabetic nephropathy. In recent years, the incidence of diabetic nephropathy in China is increasing, and the diabetic nephropathy is the main cause of end-stage nephropathy at present, and is second to glomerulonephritis. The chronic kidney disease can cause cardiovascular events, the medical cost of the chronic kidney disease is 1.8 times of that of the non-chronic kidney disease, and a heavy economic burden is caused to the individual and the society of the patient.
At present, no specific treatment method for diabetic nephropathy exists, the main principles of treatment are blood sugar, blood pressure and blood fat control and proteinuria reduction, and no effective means is available for preventing DN disease progression. Currently, Angiotensin Converting Enzyme Inhibitors (ACEIs) or angiotensin receptor Antagonists (ARBs) are the first choice for treating DN, and new studies have shown that Mineralocorticoid Receptor Blockers (MRBs) in combination with ACEIs or ARBs can help to reduce proteinuria. Novel hypoglycemic agents, such as sodium-glucose cotransporter 2(SGLT2) inhibitors, such as empagliflozin and dapagliflozin, can reduce proteinuria and reduce the occurrence of complex renal outcomes. GLP-1 agonists also have a beneficial effect on proteinuria, and liraglutide can reduce the dose-dependence of proteinuria. However, the above treatments still have limitations and adverse reactions, and a more effective treatment for DN needs to be found.
The pathogenesis of diabetes is based on yin deficiency, and excessive dryness-heat, so ancient people mostly adopt syndrome differentiation and treatment of upper, middle and lower digestions. The differentiation and classification of diabetic nephropathy and the treatment of diabetic nephropathy are not unified, and modern researches show that part of single medicines and extracts thereof such as astragalus, polygonatum polysaccharides, berberine and the like can delay the progress of diabetic nephropathy, and traditional Chinese medicine compound such as qi-tonifying, detoxifying, blood stasis-removing small compound traditional Chinese medicine, Jisheng kidney qi pills, kidney-eliminating decoction and the like can delay the progress of diabetic nephropathy through different mechanisms. However, the Chinese patent medicines on the market such as diabetes pill, Yuquan pill, etc. all focus on nourishing yin and clearing heat, tonifying qi and promoting the production of body fluid, have poor pertinence to the symptoms related to diabetic nephropathy, and the curative effect needs to be further improved.
Disclosure of Invention
The invention aims to overcome the defects of the prior art, provides the traditional Chinese medicine composition for treating diabetic nephropathy and the traditional Chinese medicine preparation prepared by adopting the traditional Chinese medicine composition, obviously improves the clinical symptoms of the diabetic nephropathy, reduces the serum creatinine, the urea nitrogen and the urine protein of a diabetic nephropathy patient, and has good kidney protection effect.
The invention provides a traditional Chinese medicine composition for treating diabetic nephropathy, which is prepared from the following traditional Chinese medicines in parts by weight: 5-30 parts of raw astragalus membranaceus, 5-20 parts of codonopsis pilosula, 5-20 parts of cornus officinalis, 5-20 parts of herba lycopi, 5-20 parts of rhizoma alismatis, 5-30 parts of radix ranunculi ternati, 10-40 parts of rhizoma smilacis glabrae, 5-20 parts of kadsura pepper stem, 5-20 parts of rhizoma dioscoreae nipponicae, 5-20 parts of trichosanthes root, 5-20 parts of angelica sinensis and 5-20 parts of curcuma zedoary.
The traditional Chinese medicine composition is prepared from the following traditional Chinese medicines in parts by weight: 15-30 parts of raw astragalus membranaceus, 10-20 parts of codonopsis pilosula, 8-20 parts of prepared cornus officinalis, 8-20 parts of herba lycopi, 5-20 parts of rhizoma alismatis, 15-30 parts of radix ranunculi ternati, 20-40 parts of rhizoma smilacis glabrae, 8-20 parts of kadsura pepper stem, 10-20 parts of rhizoma dioscoreae nipponicae, 10-20 parts of trichosanthes root, 8-20 parts of angelica sinensis and 8-20 parts of curcuma zedoary.
The traditional Chinese medicine composition is prepared from the following traditional Chinese medicines in parts by weight: 30 parts of raw astragalus membranaceus, 15 parts of codonopsis pilosula, 10 parts of cornus officinalis, 12 parts of herba lycopi, 10 parts of rhizoma alismatis, 30 parts of radix ranunculi ternati, 40 parts of rhizoma smilacis glabrae, 12 parts of kadsura pepper stem, 15 parts of dioscorea nipponica, 15 parts of trichosanthes root, 12 parts of angelica sinensis and 10 parts of curcuma zedoary.
The preparation method of the traditional Chinese medicine composition comprises the following steps: extracting with water, and making into final product.
The specific water extraction method comprises the following steps: taking the traditional Chinese medicine raw materials, adding 8-16 times (by weight) of water, decocting for 1 hour, filtering, and preparing the filtrate for later use; adding 8-16 times (by weight) of water into the filter residue, decocting for 1 hr, filtering, discarding the filter residue, mixing the previous filtrates, concentrating, drying, and making into pill, tablet, capsule, liquid, etc.
The traditional Chinese medicine composition is prepared into a traditional Chinese medicine preparation by adding pharmaceutically acceptable auxiliary materials after extracting traditional Chinese medicine raw materials, and the preparation form is one of pills, tablets, capsules, granules, soft capsules and oral liquid.
The traditional Chinese medicine composition is applied to preparing a medicine for treating diabetic nephropathy.
Radix astragali is dried root of Astragalus mongholicus (Astragalus mongholicus Bunge) belonging to Leguminosae. Mainly produced in inner Mongolia, Shanxi and Heilongjiang provinces of China. Radix astragali is warm in nature, and has effects of invigorating qi, invigorating yang, consolidating superficial resistance, arresting sweating, and promoting granulation. It can be used for treating deficiency of qi and blood, spontaneous perspiration, chronic diarrhea, proctoptosis, metroptosis, nephritis, edema, albuminuria, diabetes, and chronic ulcer. Recent researches show that the extract astragaloside IV has the effects of enhancing immune system, resisting oxidation, delaying aging, improving cardiac function, resisting virus, resisting cancer and the like.
Radix Codonopsis is in Codonopsis of Campanulaceae (Codonopsis pilosula (Franch.) Nannf.), and produced in North China at 1560 + 3100 m mountain forest edge and bush. Has neutral nature and sweet taste, has the effects of invigorating spleen and replenishing qi, quenching thirst, strengthening spleen and benefiting lung, nourishing blood and promoting fluid production, and is mainly used for treating weakness of spleen and stomach, deficiency of both qi and blood, tiredness and weakness, anorexia, thirst, long-term diarrhea and rectocele. Recent researches show that the main component polysaccharide has the effects of enhancing the immunity of organisms, resisting aging, reducing blood sugar and the like.
Fructus Corni is prepared by steaming fructus Corni (Cornus officinalis Sieb. et Zucc.) of Cornaceae, removing inner core, drying in the sun, and is distributed in Shanxi, Jiangsu, Zhejiang, Anhui, Jiangxi, Shandong, Henan, Hunan, Sichuan, Shaanxi, Gansu, etc. Sour, astringent and slightly warm, entering liver and kidney meridians. Has the efficacies of tonifying liver and kidney, astringing and relieving depletion. It is commonly used for vertigo, tinnitus, soreness and pain of waist and knees, impotence, spermatorrhea, enuresis, frequent micturition, metrorrhagia, leukorrhagia, profuse sweating, exhaustion, internal heat, and diabetes. Modern medical research shows that the dogwood has the functions of enhancing the immune system, resisting inflammation, inhibiting bacteria, reducing blood sugar, resisting shock, resisting oxidation, resisting tumors and the like.
Herba Lycopi is dried aerial part of Polygala hirsuta seedling (Lycopus lucidus Turcz. vat. hirtus Regel) belonging to Labiatae. Is distributed in most areas of China. Bitter and pungent with mild warm nature. It enters liver and spleen meridians. Has the effects of activating blood circulation, regulating meridians, removing blood stasis, eliminating carbuncle, inducing diuresis and relieving swelling. Can be used for treating menoxenia, amenorrhea, dysmenorrhea, puerperal blood stasis and abdominal pain, skin ulcer, carbuncle, toxic swelling, edema, and ascites. Modern researches show that herba lycopi can improve renal interstitial fibrosis and delay the progress of chronic renal diseases by promoting the expression of HGF and VEGF.
Alismatis rhizoma is dried tuber of Alismatis rhizoma (Alisma orientalis (Sam.) Juzep.) of Alismaceae. Sweet and cold in nature. Entering kidney and bladder meridians, promoting urination, clearing away damp-heat, and treating dysuria, edema, distention, diarrhea, oliguria, phlegm-fluid dizziness, and stranguria with astringency and pain. Modern researches show that the rhizoma alismatis water extract can obviously inhibit the formation of experimental kidney stones of rats induced by glycol and active vitamin D3.
Ranunculus ternatus (Thunb.) nakai is dried root tuber of Ranunculus ternatus (Ranunculus ternatus Thunb.) nakai of Ranunculaceae. Is distributed in Guangxi, Taiwan, Jiangsu, Zhejiang, Jiangxi, Hunan, Anhui, Hubei, Henan, etc. Sweet and pungent in flavor and warm in nature. It enters liver and lung meridians. Has the effects of reducing phlegm and resolving masses, and detoxifying and reducing swelling. It is commonly used for scrofula, subcutaneous nodule, furuncle, pyogenic infections, snake and insect bite. Modern researches show that the compound radix ranunculi ternati aqueous extract has anti-inflammatory effect.
Rhizoma Smilacis Glabrae is dried Rhizome of Smilax scobinicaulis (Glabrous Greenbrier Rhizome) of Liliaceae. Sweet and light taste, mild nature, and has the effects of removing toxic substances, eliminating dampness, and benefiting joints. It can be used for treating syphilis, stranguria with turbid urine, spasm and pain of tendons and bones, tinea pedis, furuncle, carbuncle, swelling, and lymphoid tuberculosis. Modern researches show that the glabrous greenbrier rhizome has better immunity and anti-inflammatory efficacy.
Caulis Piperis Futokadsurae is dry stem of caulis Sinomenii (Piper kadsura (Choisy)0hwi) of Piperaceae, is pungent and bitter in taste, slightly warm in nature, and enters liver meridian. Has the effects of dispelling wind-damp, dredging channels and collaterals, and relieving arthralgia, and can be used for treating anemofrigid-damp arthralgia, limb joint pain, spasm of tendons and vessels, and difficulty in flexion and extension. The effective component piperitone has antiinflammatory effect, and the futenone can antagonize human neutrophil aggregation and degranulation reaction caused by platelet activating factor, and can block rat skin vascular permeability enhancing reaction caused by activating factor, histamine, and bradykinin
Ningpo Yam rhizome, the dried rhizome of Dioscorea nipponica Makino, is mainly distributed in Liaoning, Jilin, Heilongjiang, Hebei, inner Mongolia and other places. Sweet and bitter in flavor, warm in nature, entering liver, kidney and lung meridians. Has effects in expelling pathogenic wind, removing dampness, relaxing muscles and tendons, expelling collateral obstruction, promoting blood circulation, relieving pain, and relieving cough and asthma, and can be used for treating rheumatism, numbness of joints, traumatic injury, lumbar sprain, and cough and asthma. The research shows that the effective component total saponin can obviously reduce rabbit blood cholesterol and blood pressure, delay heart rate, strengthen heart contraction amplitude, increase urine volume, reduce beta/alpha lipoprotein ratio and improve coronary circulation.
Trichosanthis radix is dry root of Trichosanthes kirilowii Maxim or Trichosanthes rosthornii Maxim of Cucurbitaceae. Distributed in Henan et al. Sweet, slightly bitter and slightly cold in taste, enters lung and stomach channels, has the efficacies of clearing heat and purging fire, promoting fluid production to quench thirst, and reducing swelling and expelling pus, and is mainly used for treating fever polydipsia, lung heat dry cough, internal heat diabetes, sore and ulcer pyogenic infections. The research shows that 5 glycan components separated from trichosanthes root can reduce the blood sugar of mice.
Angelica sinensis (Oliv.) Diels is dried root of Angelica sinensis (Oliv.) Diels) belonging to family Umbelliferae. The major production in southeast Gansu province has high yield and good quality in Min county, and is provinces such as Yunnan, Sichuan, Shaanxi, Hubei and the like. Sweet and pungent in flavor, warm in nature, entering liver, heart and spleen meridians. Has the functions of enriching blood, promoting blood circulation, regulating menstruation, relieving pain, moistening intestine and relaxing bowels. It is commonly used for blood deficiency and sallow complexion, vertigo and palpitation, irregular menstruation, amenorrhea and dysmenorrhea, deficiency cold and abdominal pain, rheumatic arthralgia, traumatic injury, carbuncle, ulcer, constipation due to intestinal dryness. The wine angelica sinensis can activate blood and promote menstruation. Can be used for treating amenorrhea, dysmenorrhea, rheumatalgia, and traumatic injury. The effective component ferulic acid has blood lipid reducing effect.
Zedoary, the root and stem of Curcuma zedoary (Curcuma aromatica Roxb. [ c.zedoaria non Rosc. ]), Guangxi Curcuma zedoary (Curcuma kwangsisensis S.G.Lee et C.F.Liang) and Curcuma wenyujin Y.H.Chen et C.Ling) of the zingiberaceae family, are distributed in Guangdong, Guangxi, Sichuan, Yunnan, etc.; pungent and bitter in flavor, warm in nature, entering liver and spleen meridians. Has the effects of promoting qi circulation, removing blood stasis, resolving food stagnation and relieving pain. It is commonly used for blood-qi and heart pain, food stagnation, abdominal distention and pain, amenorrhea due to blood stagnation, dysmenorrhea, abdominal mass and lump, and traumatic injury. Modern researches show that the curcuma zedoary has a protective effect on both liver and kidney, and the curcuma wenyujin volatile oil has a certain anti-inflammatory effect.
The traditional Chinese medicine composition comprises raw astragalus mongholicus, codonopsis pilosula, cornus officinalis, herba lycopi, rhizoma alismatis, radix ranunculi ternati, rhizoma smilacis glabrae, caulis piperis futokadsurae, rhizoma dioscoreae nipponicae, trichosanthes kirilowii, angelica sinensis and curcuma zedoary. Wherein, the astragalus root is used as a monarch drug for tonifying qi and strengthening exterior, inducing diuresis and reducing edema, the codonopsis pilosula and the dogwood fruit are used as ministerial drugs for assisting the astragalus root to tonify kidney qi, and the herba lycopi, the rhizoma alismatis, the radix ranunculi ternate, the radix trichosanthis and the rhizoma smilacis glabrae are used as ministerial drugs. The traditional Chinese medicine composition has the advantages of complete monarch, minister, assistant and guide effects, strict compatibility and mutual assistance, has the functions of reinforcing the kidney, dispelling wind, eliminating turbidity and dredging collaterals, has very obvious clinical symptoms of improving diabetic nephropathy, can reduce blood creatinine, urea nitrogen and urine protein of diabetic nephropathy patients, has a good kidney protection effect, and has a good application prospect.
Detailed Description
The present invention is further described with reference to the following examples, which are intended to be illustrative only and not to be limiting of the scope of the claims, and other alternatives which may occur to those skilled in the art are within the scope of the claims.
Example 1: taking 5g of raw astragalus membranaceus, 20g of codonopsis pilosula, 5g of prepared cornus officinalis, 20g of herba lycopi, 5g of rhizoma alismatis, 30g of radix ranunculi ternati, 10g of rhizoma smilacis glabrae, 20g of kadsura pepper stem, 5g of dioscorea nipponica, 20g of radix trichosanthis, 5g of angelica sinensis and 20g of rhizoma zedoariae, adding water with the weight being 16 times that of medicinal materials, decocting for 1 hour, filtering, adding water with the weight being 8 times that of the medicinal materials into medicinal residues, decocting for 1 hour, combining water decoction liquid obtained in two times, filtering, concentrating the filtrate, drying in vacuum to obtain extract dry powder, adding dextrin, granulating by a wet method with 80% ethanol, and.
Example 2: taking 30g of raw astragalus membranaceus, 5g of codonopsis pilosula, 20g of prepared cornus officinalis, 5g of herba lycopi, 20g of rhizoma alismatis, 5g of radix ranunculi ternati, 40g of rhizoma smilacis glabrae, 5g of kadsura pepper stem, 20g of dioscorea nipponica, 5g of radices trichosanthis, 20g of angelica sinensis and 5g of rhizoma zedoariae, adding water with the weight being 16 times that of the raw materials, decocting for 1 hour, filtering, adding water with the weight being 8 times that of the raw materials into dregs of a decoction, decocting for 1 hour, combining water decoction solutions of the two times, filtering, concentrating the filtrate, drying in vacuum to obtain extract dry powder, adding starch.
Example 3: taking 30g of raw astragalus membranaceus, 15g of codonopsis pilosula, 10g of prepared cornus officinalis, 12g of herba lycopi, 10g of rhizoma alismatis, 30g of radix ranunculi ternati, 40g of rhizoma smilacis glabrae, 12g of kadsura pepper stem, 15g of dioscorea nipponica, 15g of radix trichosanthis, 12g of angelica sinensis and 10g of curcuma zedoary, adding water with the weight being 16 times that of the raw materials, decocting for 1 hour, filtering, adding water with the weight being 8 times that of the raw materials into medicinal residues, decocting for 1 hour, combining decoction liquid obtained in two times, filtering, concentrating the filtrate, performing spray drying to obtain extract dry powder, adding dextrin into the extract.
Example 4: taking 30g of raw astragalus membranaceus, 15g of codonopsis pilosula, 10g of prepared cornus officinalis, 12g of herba lycopi, 10g of rhizoma alismatis, 30g of radix ranunculi ternati, 40g of rhizoma smilacis glabrae, 12g of kadsura pepper stem, 15g of dioscorea nipponica, 15g of radix trichosanthis, 12g of angelica sinensis and 10g of curcuma zedoary, adding water with the weight being 16 times that of the raw materials, decocting for 1 hour, filtering, adding water with the weight being 8 times that of the raw materials into medicinal residues, decocting for 1 hour, combining water decoction of the two times, filtering, concentrating the.
Example 5: taking 30g of raw astragalus membranaceus, 15g of codonopsis pilosula, 10g of prepared cornus officinalis, 12g of herba lycopi, 10g of rhizoma alismatis, 30g of radix ranunculi ternati, 40g of rhizoma smilacis glabrae, 12g of kadsura pepper stem, 15g of dioscorea nipponica, 15g of radix trichosanthis, 12g of angelica sinensis and 10g of curcuma zedoary, adding water with the amount which is 16 times of the weight of the medicinal materials, decocting for 1 hour, filtering, adding water with the amount which is 8 times of the weight of the medicinal materials into medicinal residues, decocting for 1 hour, combining decoction liquid obtained in two times, filtering, concentrating the filtrate, spray.
Example 6: clinical observation of the invention for treating diabetic nephropathy
1. The source of the cases is: 80 diabetic nephropathy patients who are treated by special outpatient service or hospitalized in 3 months of nephrology department from 2018 to 2020 in Nanjing, the patients who are treated and enter the treatment group are all in accordance with the syndrome of kidney deficiency, dampness and turbidity and blood stasis, and the patients who are in accordance with the inclusion standard are divided into a treatment group and a control group according to a random control principle, wherein 40 patients in each group.
2. Diagnostic criteria for diabetic nephropathy: according to the diagnosis standard of diabetic nephropathy, which is issued by the endocrine society of Chinese medical society for Endocrinology 2016 (Chinese adult diabetes nephropathy clinical diagnosis specialist consensus), and improved global kidney disease prognosis organization KDIGO (CKD assessment and management clinical practice guideline 2012), the diagnosis standard belongs to stage III and stage IV DN as observation objects according to the Mogensen staging standard. The method specifically comprises the following steps: firstly, the exact history of diabetes mellitus is provided; ② fundus retinopathy; ③ the quantification of urinary microalbumin is more than 30mg/24h or the urinary albumin/urinary creatinine is more than 30 mg/mmol. And the eGFR is more than 10 ml/min.
3. The treatment grouping method comprises the following steps: before selection, the basic physical signs are stable by treatment of limiting protein intake, giving high-quality low-protein diet, controlling blood sugar, reducing blood pressure and the like, and the cases meeting the selection conditions enter the test. The selected cases were as follows 1: 1 were randomly divided into treatment and control groups. In this study, 2 patients were dropped from the treatment group, 38 patients were treated, and 40 patients were compared.
(1) Basic treatment: performing related basic knowledge propaganda and education on the patient; a low salt, low fat, high quality, low protein diet; the dosage of the oral hypoglycemic agent or insulin is determined according to specific disease conditions, so that the blood sugar reaches the standard and the occurrence of low blood sugar is avoided, the fasting blood sugar is less than or equal to 7.1mmol/L, the blood sugar after 2 hours of meal is less than 11.1mmol/L, and the glycosylated hemoglobin is less than 7 percent.
(2) Control group treatment: at the same time as the basic treatment, hypertensive patients were given irbesartan 150mg 1 time a day according to blood pressure conditions. Patients with serum creatinine >265umol/l select non-ACEI, ARB antihypertensive drugs to control blood pressure.
(3) Treatment group treatment: non-ACEI, ARB class drugs were selected for hypotension in the basal treatment. And the oral liquid prepared in example 4 was administered. The medicine is taken in the morning and evening for 2 times, 20ml each time, and the treatment course is 8 weeks.
Note: p <0.01 compared to the matched sample t test used in the group before treatment. Compared with the control group after treatment, the delta P is less than 0.05, and the delta P is less than 0.01.
Note: p <0.05, P <0.01, compared to the pretreatment pair in this group. Compared with the control group after treatment, the delta P is less than 0.05.
The above clinical applicationExperiments show that the invention can reduce Scr (mu mol/L), BUN (mmol/L), ACR (mg/gCr) and MALb (mg/L) and increase GFR (ml/min)*1.73m2) Compared with a control group, the composition has significant difference, which shows that the composition has good treatment effect on diabetic nephropathy.
Example 7: pharmacodynamic experiments of the invention
1. Apparatus and materials
1.1 Main instruments: HEA-230 glucometer (OMRON, Japan), blood glucose test paper (OMRON, Japan), 5415R type centrifuge (Eppendorf, Germany), Sartorius electronic balance (Sidoris scientific instruments (Beijing) Co., Ltd.), Hitachi OLYMPUS automated biochemical analyzer (model 7600, Nanjing Sanko Co., Ltd.).
1.2 reagent: streptozotocin (STZ, SIGMA); example 4 the resulting oral liquid formulation was prepared.
1.3 Experimental animals: 60 healthy male Sprague-Dawley (SD) rats, clean grade, 4-6 weeks old, body weight approximately 140-: SYXK (threo) 2017-0040. After the adaptive feeding is carried out for one week, the experiment is carried out without adverse reaction.
2. Experimental methods
2.1, molding: the method comprises the following steps of grouping 50 SD rats according to a random digital table, wherein 10 rats in a normal group (N group) and 50 rats in a molding group are adaptively fed for 7 days, fasting for 12 hours, weighing and preparing a diabetic nephropathy model, carrying out left-side intraperitoneal injection on the model group at one time according to 55mg/kg of a 1% Streptozotocin (STZ) solution, carrying out left-side intraperitoneal injection on the normal group (N group) by using an equivalent amount of physiological saline, carrying out standard diet on each group, periodically replacing padding and disinfecting cages. And (3) continuously measuring random blood sugar for 3 days 72 hours after the STZ solution is injected into the model, wherein the blood sugar value is more than 16.7mmol/L, the preparation of the Diabetes Mellitus (DM) model is successful, the persons who do not reach the standard are repeatedly injected into the left abdominal cavity of the STZ solution with the concentration of 55mg/kg for 1 time, and the persons who reach the standard in blood sugar are repeatedly measured after 5 days and enter the subsequent Diabetic Nephropathy (DN) model. After the rats which are successfully molded by DM are fed for 1 week, the random blood sugar is more than 16.7mmol/L, the urine volume is 1.5 times or more of that of the normal group (N group), and the 24h urine protein is 1.5 times or more of that of the normal group (N group), so that the model DN model is successfully prepared, and the molded rats which have the index which is not up to the standard are removed.
2.2 grouping and administration: 40 rats of DN model are randomly divided into 10 model groups (DN group), 10 low-dose groups of Chinese herbal compound, 10 medium-dose groups of Chinese herbal compound (GSM group) and 10 high-dose groups of Chinese herbal compound (GSH group). The dosage of the rat is calculated according to the body weight per kilogram of the animals and the human bodies (6.25 times of the human bodies), and the low, medium and high dosage groups of the traditional Chinese medicine compound group adopt the medicinal components prepared in the example 1. The group N and the group DN are administrated by 0.1ml/10g normal saline, the compound Chinese medicine components are administrated according to low, medium and high concentrations (respectively 10.99, 21.98 and 43.96g/kg) of the tested medicine respectively, the administration volume is 0.1ml/10g, the administration is carried out for 1 time every day, and the administration is carried out continuously for 6 weeks.
2.3 observation indexes: blood sugar: and detecting the random blood sugar of the rat by using an HEA-230 glucometer respectively on 0 day, 21 days and 42 days after the molding is successful. 24-hour urinary protein quantification: after the model is formed and after the medicine intervention is finished, urine is collected for 24 hours by using a metabolism cage respectively, the urine volume is recorded, and the 24-hour urine protein content is measured by a radioimmunoassay. Renal function: blood samples were collected in the clinical laboratory of Hospital, Nanjing, and Scr and BUN were detected by an OLYMPUS automatic biochemical analyzer. Observation of kidney histopathology: the rat is anesthetized, then the cervical vertebra is removed, the right kidney is taken, the capsule is removed, the kidney blood vessel is irrigated by normal saline to remove blood, the filter paper is dried, the rat is cut along the sagittal median line, 1/2 is placed into 4 percent paraformaldehyde fixing solution, the rat is embedded by normal paraffin after 48 hours, the rat is sliced by 4um continuously, the rat is stained by HE, and the pathological and histological changes of the kidney are observed under a light mirror.
2.4 statistical treatment: statistical analysis was performed using SPSS26.0 software. The measured data are expressed in terms of (X +/-S), two-by-two comparison adopts t test, and multiple groups of comparison adopts one-factor variance analysis. P <0.05 is statistically significant.
3. Results of the experiment
3.1 comparison of fasting plasma glucose in rats of each group (Table 3)
Table 3 comparison of random blood glucose changes (mmol/L) (X ± S) (n ═ 10) in each group of rats
Note: compared with normal control group, the delta P is less than 0.01, and compared with model group, the color P is less than 0.05
Compared with the normal control group, the blood sugar of the mice in the rest groups is obviously increased (P <0.01), and the blood sugar of the administration groups is not obviously different (P > 0.05). Over time, blood glucose in each administration group was reduced compared to the model group, and the difference was statistically significant (P < 0.05).
3.2 conditions of 24-hour urine protein in rats of each group (Table 4)
Table 4 comparison of 24h urine protein (mg/24h) (X ± S) (n ═ 10) for each group of rats
Note: compared with a normal control group, the delta P is less than 0.01, and compared with a model group, the quantitative rate of the urine protein of each group is improved, the decrease is most obvious in a high-dose group of the tested traditional Chinese medicine, and the # P is less than 0.01.
3.3 comparison of serum levels of Scr and BUN in rats of each group (Table 5)
Table 5 serum Scr, BUN levels (X ± S) of rats in each group (n ═ 10)
Note: in comparison with the normal group,#P<0.01, Δ P compared to model group<0.05。
3.4 pathological integral comparison of rat kidney in each group (Table 6)
Table 6 pathological integral of rat kidney (X ± S) (n ═ 10)
Note: in comparison with the set of models,ΔP<0.05。
and (4) conclusion: the invention can effectively reduce the blood sugar, blood creatinine, urea nitrogen and 24-hour urine protein of a diabetic nephropathy rat, and improve the kidney injury, and the curative effect of the invention is related to the drug dosage.
Claims (6)
1. A traditional Chinese medicine composition for treating diabetic nephropathy is characterized by being prepared from the following traditional Chinese medicines in parts by weight: 5-30 parts of raw astragalus membranaceus, 5-20 parts of codonopsis pilosula, 5-20 parts of cornus officinalis, 5-20 parts of herba lycopi, 5-20 parts of rhizoma alismatis, 5-30 parts of radix ranunculi ternati, 10-40 parts of rhizoma smilacis glabrae, 5-20 parts of kadsura pepper stem, 5-20 parts of rhizoma dioscoreae nipponicae, 5-20 parts of trichosanthes root, 5-20 parts of angelica sinensis and 5-20 parts of curcuma zedoary.
2. The traditional Chinese medicine composition as claimed in claim 1, which is prepared from the following traditional Chinese medicines in parts by weight: 15-30 parts of raw astragalus membranaceus, 10-20 parts of codonopsis pilosula, 8-20 parts of prepared cornus officinalis, 8-20 parts of herba lycopi, 5-20 parts of rhizoma alismatis, 15-30 parts of radix ranunculi ternati, 20-40 parts of rhizoma smilacis glabrae, 8-20 parts of kadsura pepper stem, 10-20 parts of rhizoma dioscoreae nipponicae, 10-20 parts of trichosanthes root, 8-20 parts of angelica sinensis and 8-20 parts of curcuma zedoary.
3. The traditional Chinese medicine composition according to claim 2, which is prepared from the following traditional Chinese medicines in parts by weight: 30 parts of raw astragalus membranaceus, 15 parts of codonopsis pilosula, 10 parts of prepared cornus officinalis, 12 parts of herba lycopi, 10 parts of rhizoma alismatis, 30 parts of radix ranunculi ternati, 40 parts of rhizoma smilacis glabrae, 12 parts of kadsura pepper stem, 15 parts of rhizoma dioscoreae nipponicae, 15 parts of trichosanthes root, 12 parts of angelica sinensis and 10 parts of curcuma zedoary.
4. The traditional Chinese medicine composition according to any one of claims 1 to 3, which is prepared by a method comprising the following steps: extracting with water, and making into final product.
5. The Chinese medicinal composition according to any one of claims 1 to 3, wherein the Chinese medicinal preparation is prepared by extracting the Chinese medicinal materials and adding pharmaceutically acceptable adjuvants, and is in the form of pill, tablet, capsule, granule, soft capsule or oral liquid.
6. The use of a Chinese medicinal composition according to any one of claims 1-3 in the preparation of a medicament for the treatment of diabetic nephropathy.
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