CN104042682A - Traditional Chinese medicine composition for treating diabetic complication pneumonia - Google Patents
Traditional Chinese medicine composition for treating diabetic complication pneumonia Download PDFInfo
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Abstract
The invention relates to a traditional Chinese medicine composition for treating diabetic complication pneumonia. The composition comprises wild buckwheat extractive and at least one alpha-glycosidase inhibitor. Accidentally discovered by clinic and pharmacology, the composition has functions of treating diabetes and diabetic nephropathy and is in favor of improving diabetic complication pharyngitis and diabetic complication pneumonia through combined action of inhibition of wild buckwheat and glycosidase.
Description
Technical field
The present invention relates to the medicine of a kind of orally taken for curing diabetes and diabetes complicated pneumonia; Belong to natural medicine field.
Background technology
Diabetes complicated pneumonia, pneumonia has been one of common complication of diabetes.Old-aged diabetic's Complicating Pneumonia In Patients very easily causes multiple organ dysfunction, and then occurs organ failure, serious harm patient life security.
Diabetes merge scarcely typical case of symptoms of pneumonia, and patient's onset symptoms often shows as that heating, dysphoria, disturbance of consciousness, uncomfortable in chest, cardiopalmus, appetite are poor, nauseating, vomiting etc., and its cough is often not obvious, even there is no cough.But, in the time of health check-up, can find obvious pneumonia feature, be called clinically diabetes and merge asymptomatic pneumonia.
The influence factor of the asymptomatic pneumonia of diabetes mainly contains following 2 points: the sick neuropathy merging of urine can make coughre flex suppress, and is the main cause that asymptomatic pneumonia forms; When infection, easily there is even hyperosmolar coma of ketoacidosis, cause that thus non-respiratory symptom can cover respiratory symptom, make respiratory symptom not obvious, outstanding on the contrary.
Diabetes patient is easy to catch cold, and we also know that flu is also easily to cause pneumonia.Data show, the risk that diabetes patient suffers from an inflammation of the lungs, be 6 times of Healthy People, and case fatality rate is 3 times of Healthy People.
Therefore, finding to have the prodromal active drug for the treatment of diabetes pneumonia, is the needs of clinical treatment.
Diabetic nephropathy, is because diabetic sugar Developmental and Metabolic Disorder is the glomerular sclerosis due to main cause, and accompanies urine protein content to exceed normally, is called diabetic nephropathy.It is a kind of chronic complicating diseases of the serious and hazardness maximum that causes of diabetes, is that diabetes general microangiopathies one of shows, and Clinical symptoms is albuminuria, gradual renal function injury, and hypertension,, there is severe renal nonfunction late period in edema.And this disease is also one of major causes of death of diabetics.
The at present clinical effectively natural drug for the treatment of diabetic nephropathy that still lacks.
Rhizoma Fagopyri Dibotryis: be polygonaceae plant Rhizoma Fagopyri Dibotryis Fagopyrum dibotrys(D.Don) dry rhizome of Hara.
It is generally acknowledged that Rhizoma Fagopyri Dibotryis has heat-clearing and toxic substances removing, the effect of evacuation of pus blood stasis dispelling.1932 pages of " Chinese crude drug " the 32nd the 12nd phases of volume, the small sample clinical trial that a kind of multicomponent Chinese prescription that contains Rhizoma Fagopyri Dibotryis is used for the treatment of early diabetic nephropathy is disclosed.
Rhizoma Fagopyri Dibotryis rhizome is containing the former cyanidin of double focusing (dimeric Procyani-din), hecogenin (hecogenin), cupreol (β-sitosterol), can obtain the glycoside of p-coumaric acid (p-coumaric acid), ferulic acid (ferulic acid) and glucose (glucose) after tannin (tannin) and a kind of hydrolysis.Also contain left-handed epicatechin (epicatechin), 3-galloylepicatechin (3-galloyl epicatechin), 3,3 of former cyanidin (procyanidin) B-2, B-4 and former cyanidin B-2 '-digallic acid ester (3-3 '-digalloylprocyanidin).
Have report: Rhizoma Fagopyri Dibotryis root water decoction 20g(crude drug)/(kgd) and 13.3g(crude drug)/(kg.d) gavage, continuously 10d, all has to Mice Bearing Lewis Lung Cancer and cervical carcinomal U14 the inhibitory action showing, the curative effect of female mice compared with male mice for well.
Utilize grafting under Mouse Kidney cyst membrane (SRCA), relatively cancerous lung tissue is transplanted the antitumaous effect of front and back stereomutation with prediction and evaluation Rhizoma Fagopyri Dibotryis extract gold E and CD1.
Rhizoma Fagopyri Dibotryis root element (Fagopyrum Cymosum Rootin, FCR) be the comprehensive tannin mixture of a class proposing from Rhizoma Fagopyri Dibotryis root, when every 1ml concentration is 125 μ g, to adenocarcinoma of lung GLC), squamous carcinoma of the cervix HeLa), the suppression ratio of nasopharyngeal squamous cell carcinoma (KB) Growth of Cells is respectively 84.5%, 78.9 %, 100%, makes film, RNA, DNA metabolism, the karyokinesis damaged of cancerous cell.
Cortex Mori is the root bark of moraceae plants Mulberry Morus alba L..
Pharmacological research shows that Rhizoma Fagopyri Dibotryis and composition thereof are without obvious vitro antibacterial activity, illustrates that this medicine does not belong to traditional antimicrobial drug.
Common healthy population upper respiratory tract infection, comprise viral influenza, use antibiotic often can not effectively improve prognosis, and diabetics upper respiratory tract infection, comprise viral influenza, early application antibiosis have and reduces the clinical income that complication occurs, still, the antibiotic of diabetics, diabetic nephropathy patient uses, and clinical have all multi-risk Systems.
Summary of the invention
The object of the present invention is to provide a kind of composite preparation of natural drug, for diabetics control blood glucose, simultaneously can be used for treating diabetes merge pneumonia, diabetes merge upper respiratory tract infection, delay diabetic nephropathy process.
The present invention all selects natural Chinese medicinal herb to make suitable medicine.
The invention provides a kind of compositions for the treatment of chronic complicating diseases of diabetes, formed by effective ingredient and pharmaceutically acceptable carrier, it is characterized in that:
A kind of Chinese medicine composition for the treatment of diabetes complicated pneumonia, formed by effective ingredient and pharmaceutically acceptable carrier, it is characterized in that: described effective ingredient is to come from: one has alpha-glucosidase inhibiting medical herb position and Rhizoma Fagopyri Dibotryis composition, described in there is the inhibiting medical herb of alpha-glucosidase position and comprise: Ramulus Mori, Cortex Mori, Folium Nelumbinis extract one or more.
Described a kind of Chinese medicine composition for the treatment of diabetes complicated pneumonia, is characterized in that: described have the inhibiting medical herb of an alpha-glucosidase position, and the Cortex Mori total alkaloid content of Cortex Mori extract is 10% 40%.
Described a kind of Chinese medicine composition for the treatment of diabetes complicated pneumonia, is characterized in that: in the preparation of said composition, contain the wild buttocks tail of epicatechin and 1-deoxidation mycin simultaneously.
Described a kind of Chinese medicine composition for the treatment of diabetes complicated pneumonia, is characterized in that: by medical material weight portion: 1 part of Cortex Mori: Rhizoma Fagopyri Dibotryis 2-4 part is used in conjunction with.
Described a kind of Chinese medicine composition for the treatment of diabetes complicated pneumonia is treated the application in medicine for treating diabetic nephropathy in preparation.
technique effect of the present invention:
Experimental example 1:
The impact of Cortex Mori-Rhizoma Fagopyri Dibotryis extract on diabetic nephropathy rats
1.1.1 the purebred rat of laboratory animal SD, male, and 60, body weight 200g scholar 20g.
2 1.1.2 experimental drug Cortex Mori-Rhizoma Fagopyri Dibotryis extract extractum, are evaporated to every milliliter contained material 2.48g through routine decoction, filtration, water-bath, are placed in 4 DEG C of Refrigerator stores for subsequent use;
Contrast medicine: lotensin, gliquidone.
experimental technique
1.2.1 model copy and grouping administration
Rat adaptability is fed one week, after glucose in urine, urine protein qualitative detection are negative, randomly draws 9 as Sham-operated control group (A group, be Normal group).All rats are with 10% chloral hydrate 3.5ml/kg intraperitoneal injection of anesthesia, preserved skin, and routine disinfection, at back, 1～1.5cm otch is done in Zuo Shen district.Model group rat exposes left kidney, peels off kidney fat and adrenal gland, and the left hilus renalis blood vessel of ligation, excises left kidney, sews up the incision.Iodophor disinfection, erythromycin ointment is smeared wound, once a day.Postoperative 1 week, model group was pressed 50mg/kg body weight intraperitoneal injection STZ, used before use 0.1mol/L sodium citrate buffer (PH4.4) to be immediately made into 2%STZ solution.Rats in normal control group, the isodose sodium citrate buffer of lumbar injection.
After 72h, survey blood glucose through tail venous blood sampling, blood glucose > 16.7mmol/L is that DM model is set up.Postoperative one week, randomly draw two for every group and survey microdose urine protein > 15 μ g/ml, determine that DN model forms.
Rat after modeling success is divided into 3 groups at random, is defined as 15 of pathologic group (B group), 15 of Cortex Mori-Rhizoma Fagopyri Dibotryis extract treatment groups (C group), 15 of western medicine groups (D group) with way of drawing lots.A, B group is given respectively distilled water 2ml gavage, and C group is to Cortex Mori-Rhizoma Fagopyri Dibotryis extract decocting liquid 2ml(24g/kg) gavage.D group is to lotensin (distilled water dissolves 1.5mg/kg) and gliquidone (distilled water dissolves 10mg/kg) suspension 2ml gavage.The equal 1 time/d of above administration, continues 10 weeks altogether.
1.2.2 observation index and method
(1) 10 week renal hypertrophy index (kidney weight/body weight) (KW/BW%)
(2) renal function (BUN, Scr).
(3) 24h urine protein quantitation (24hUpr),
2microglobulin.
2 results:
The comparison of the loose index of each group rat kidney, renal function after 2.1 treatments.The results are shown in Table 1.
The comparison (± S) of the loose index of the each group of table 1 rat kidney, renal function
The loose index of B group rat kidney, BUN, Scr all have significant difference (P<0.01) compared with A group; C group compares with B group, and renal hypertrophy index, BUN, Scr obviously reduce, and have significant difference (P<0.01).D group compares with B group, and These parameters also has utmost point significant difference (P<0.01).C group compares with D group, both no significant differences (P > 0.05).
Illustrate that the treatment of Cortex Mori-Rhizoma Fagopyri Dibotryis extract has more satisfactory curative effect improving aspect the loose index of rat kidney, kidney merit.
The comparison of each group rat 24hUpr, 2 microglobulins, α-SMA after 2.2 treatments.In table 2.
The comparison (± S) of the each group of table 2 rat 24hUpr, 2 microglobulins, α-SMA
B group rat 24hUpr, 2 microglobulins all have significant difference (P<0.01) compared with A group; C group compares with B group, and 24hUpr, 2 microglobulins obviously reduce, and have utmost point significant difference (P<0.01).D group compares with B group, and 24hUpr, 2 microglobulins also obviously decline, and difference has significance (P<0.01); C group compares with D group, both no significant differences (P > 0.05).
This experimental result shows: after the treatment of Cortex Mori-Rhizoma Fagopyri Dibotryis extract, rat model Pathological changes to be found, its glomerular sclerosis and matrix secreted situation are all light than pathologic group.It can be said that bright this can treat diabetic nephropathy, protection renal tissue, improves and recovers the therapeutic purposes of renal function.
Experimental example 2:
The therapeutical effect of Cortex Mori-Rhizoma Fagopyri Dibotryis extract to diabetes pharyngitis
Object: the further Clinical efficacy and safety of objective evaluation Sang Jin drop pill (Jinzhou Bo Ze medical sci-tech development corporation, Ltd. provides, and preparation method is with reference to embodiment) treatment acute pharyngitis.
Method: we have carried out clinical observation year January in May, 2012 to 2013.
The test method that adopts random packet, double blinding, multicenter contrast, treatment group is totally 105 examples, gives Sang Jin oral drip-ball; Matched group is totally 34 examples, gives jinlianhua pian oral.Observe altogether 5 days for two groups.
Diagnostic criteria
Western medicine diagnose standard
1. medical history has diabetic history, suffer from cold in the recent period, be heated, wet, overwork, tobacco and wine be excessive, and various physics or chemistry waits stimulation inducement.
2. symptom
Primary symptom pharyngalgia or odynophagia, pharyngeal dry, scorching hot.
The sense of inferior disease general malaise, heating, fear of cold, extremities aching pain, inappetence.
3. check
Pharyngeal mucosa hyperemia, color is scarlet.
Pharynx rear wall lymph follicle and lateral pharyngeal band redness or pharyngeal mucous membrane pus point are dispersed in distribution.
Outstanding heap soil or fertilizer over and around the roots is hung down, soft palate is red and swollen.
Throat swab is cultivated pathogenic bacterium or feminine gender.
When diagnosis, must there is acute attack, possess above part or all of symptom, and have 1 or 1 to check above finding positive sign, diagnosable.
Curative effect judgement:
1, patient's tcm symptom, tongue, arteries and veins situation of change.Tcm syndrome comprises that pharyngalgia, dry pharynx and pharyngeal discomfort, pharyngeal burning sensation, fever with chills, headache, malasia, cough are coughed up phlegm, yellowish or reddish urine, be hard and dry, pharyngeal mucosa hyperemia, tonsil redness, cheek enlargement, submandibular lymph nodes enlargement pain.
2, the observation of local sign.
3, the test of body temperature.
4, routine blood test (total white blood cells and differential counting).
Record once above 1,2,3 every day, 4 before test, the each record in end of the final point once.
Result: treatment group clinical cure 26 example (24.76%) 59 examples (56.16%), effective 59 examples (56.16%), effective 15 examples (14.29%), invalid 5 examples (4.76%), total obvious effective rate is 80.95%, total effective rate is 95.24%; Matched group clinical cure 9 examples (26.47%), effective 11 examples (32.35%), effective 10 examples (29.71%), invalid 4 examples (11.47%), total obvious effective rate is 58.82%, total effective rate is 88.33%.Ridit inspection, U=0.0430, P < 0.05, has significant difference.Traditional Chinese medical science disease curative effect: treatment group clinical cure 33 examples, effective 42 examples, effective 26 examples, invalid 4 examples, total obvious effective rate is 71.43%, total effective rate is 96.19%; Matched group clinical cure 9 examples, effective 13 examples, effective 7 examples, invalid 5 examples, total obvious effective rate is 64.71%, total effective rate is 85.29%.Ridit analyzes, U=0.0425, and P < 0.05, has significant difference.
Result shows, Sang Jin drop pill has better reduction diabetes pharyngitis patient blood leukocytes effect (P < 0.05) compared with jinlianhua pian.
Conclusion: through observing, have no obvious adverse reaction and toxic and side effects after treatment group patient takes medicine; Observed result shows, Sang Jin drop pill has better clinical efficacy to diabetes pharyngitis, and the two has good safety.
Detailed description of the invention:
Embodiment 1:
The preparation of Sang Jin drop pill:
Cortex Mori 500g
Rhizoma Fagopyri Dibotryis 1000g
Folium Mori, Rhizoma Fagopyri Dibotryis are with 6 times of amount 80% alcohol reflux secondaries, and each 0.5 hour, merge extractive liquid,, filtered, and filtrate is concentrated into relative density 1.35～1.40(50 DEG C) thick paste,
Add in the edible rapeseed oil of removing moisture and foam, mix, dripping under 58～70 DEG C of conditions, makes condensed fluid with the aqueous paraffin wax of 12 DEG C, and drop is aqueous paraffin wax to the greatest extent, puts in silica gel drier and is dried, and to obtain final product.
Embodiment 2,
Cortex Mori 500g
Rhizoma Fagopyri Dibotryis 2000g
Folium Mori, Rhizoma Fagopyri Dibotryis are with 12 times of amount 75% alcohol reflux secondaries, each 1 hour, merge extractive liquid,, filtered, filtrate is concentrated into relative density 1.35～1.40(50 DEG C) thick paste, add in the Macrogol 4000 of melting and the mixture of polyethylene glycol 6000, mix, dripping under 58～70 DEG C of conditions, make condensed fluid with the aqueous paraffin wax of 12 DEG C, drop is aqueous paraffin wax to the greatest extent, puts in silica gel drier and is dried, and to obtain final product.
Embodiment 3,
Cortex Mori 500g
Rhizoma Fagopyri Dibotryis 1000g
Folium Mori, Rhizoma Fagopyri Dibotryis are with 8 times of amount 75% alcohol reflux secondaries, each 1.5 hours, merge extractive liquid,, filtered, filtrate is concentrated into relative density 1.35～1.40(50 DEG C) thick paste, add in the Macrogol 4000 of melting and the mixture of polyethylene glycol 6000, mix, dripping under 58～70 DEG C of conditions, make condensed fluid with the aqueous paraffin wax of 12 DEG C, drop is aqueous paraffin wax to the greatest extent, puts in silica gel drier and is dried, and to obtain final product.
Embodiment 4,
Folium Mori 1500g
Rhizoma Fagopyri Dibotryis 1000g
Folium Mori 2000g, add 8～12 times of water gagings, decocting, 60～100 DEG C of heating, stir 1～2 hour, filter, after filtrate high speed centrifugation, polysulfonamides membrane filtration, be concentrated into relative density 1.35～1.40(50 DEG C) thick paste, Rhizoma Fagopyri Dibotryis with 8 times amount 75% alcohol reflux secondaries, each 1.5 hours, merge extractive liquid,, filter, filtrate is concentrated into relative density 1.35～1.40(50 DEG C) thick paste, merge with above-mentioned thick paste; Add in the Macrogol 4000 of melting and the mixture of polyethylene glycol 6000, mix, dripping under 58～70 DEG C of conditions, makes condensed fluid with the aqueous paraffin wax of 12 DEG C, and drop is aqueous paraffin wax to the greatest extent, puts in silica gel drier and is dried, and to obtain final product.
Embodiment 5,
Folium Mori 1500g
Rhizoma Fagopyri Dibotryis 1000g
Folium Mori 2000g, add 8～12 times of water gagings, decocting, 60～100 DEG C of heating, stir 1～2 hour, filter, after filtrate high speed centrifugation, polysulfonamides membrane filtration, be concentrated into relative density 1.35～1.40(50 DEG C) thick paste, Rhizoma Fagopyri Dibotryis with 8 times amount 75% alcohol reflux secondaries, each 1.5 hours, merge extractive liquid,, filter, filtrate is concentrated into relative density 1.35～1.40(50 DEG C) thick paste, merge with above-mentioned thick paste; Add the adjuvant such as starch to granulate, dry, granulation 500g and get final product.
Embodiment 6,
The preparation of Sang Jin tablet
Folium Mori 1500g
Rhizoma Fagopyri Dibotryis 2500g
Folium Mori are dried, pulverize as coarse powder, with extraction, filter, obtain extracting solution; 2) ultrafiltration: said extracted liquid is made to hyperfiltration treatment, collect gained filtrate; 3) concentrated: by step 2) gained filtrate carries out concentration by NF membrane or reverse osmosis membrane, obtains concentrated solution; 4) dry: concentrated solution is dried, is pulverized, obtain described Folium Mori extract,
Depletion Semen Fagopyri Esculenti decoction pieces, with 8 times amount 75% alcohol reflux secondaries, each 1.5 hours, merge extractive liquid,, filter, filtrate is concentrated into relative density 1.35～1.40(50 DEG C) thick paste, for subsequent use
Prepared Folium Mori extract, Rhizoma Fagopyri Dibotryis thick paste and adjuvant are made to tablet:
Folium Mori-Rhizoma Fagopyri Dibotryis extract 195g,
Microcrystalline Cellulose 270g,
Mannitol 272g,
Magnesium stearate 8g,
PVP K30 2g,
Folium Mori-Rhizoma Fagopyri Dibotryis extract filler microcrystalline Cellulose was waited to 120 mesh sieves, for subsequent use; PVP K30 is dissolved in to 70% alcoholic solution, is made into w/v and is 2% PVP K30 alcoholic solution, for subsequent use; By Folium Mori-Rhizoma Fagopyri Dibotryis extract, filler microcrystalline Cellulose, mannitol, after mix homogeneously, with above-mentioned PVP K30 alcoholic solution 60ml soft material processed for subsequent use, 20 mesh sieves are granulated, 60 ° of C are dried 20 minutes, and granulate, adds magnesium stearate lubricant, fully tabletting and get final product after mix homogeneously, every heavy 0.4g, one time 1,3 times on the one.
Embodiment 7,
The assay of the wild buttocks tail of epicatechin and 1-deoxidation mycin in Mulberry gold grain
Folium Mori 1500g
Rhizoma Fagopyri Dibotryis 1000g
Folium Mori 2000g, add 8～12 times of water gagings, decocting, 60～100 DEG C of heating, stir 1～2 hour, filter, after filtrate high speed centrifugation, polysulfonamides membrane filtration, be concentrated into relative density 1.35～1.40(50 DEG C) thick paste, Rhizoma Fagopyri Dibotryis with 8 times amount 75% alcohol reflux secondaries, each 1.5 hours, merge extractive liquid,, filter, filtrate is concentrated into relative density 1.35～1.40(50 DEG C) thick paste, merge with above-mentioned thick paste; Add the adjuvants such as starch to granulate, dry, granulation 500g, is distributed into every bag of 5g, for three batches, learns test for content assaying method with legal system.
Epicatechin assay:
It is appropriate that epicatechin reference substance is got in the preparation of reference substance solution, accurately weighed, makes the epicatechin solution of every 1 mL containing 26.88# μ g with acetonitrile-water (10:90) mixed solution, to obtain final product.
Depletion Semen Fagopyri Esculenti granule 20 g, porphyrize, get approximately 3 g, accurately weighed, put into the filter paper of preparation, after tightly wrapping, put into apparatus,Soxhlet's, with 50 mL ethanol extraction 6 h, let cool extracting solution is shaken up, filter, precision measures subsequent filtrate 25 mL, be evaporated near dry, residue adds acetonitrile-water (10:90) mixed solution gradation washing, washing liquid is transferred in 10 mL measuring bottles, add acetonitrile-water (10:90) mixed solution to scale, shake up, centrifugal 5 min of 3000 r/min, precision measures supernatant 5 mL, be added on polyamide column (30～60 orders, internal diameter 1.0 cm, column length 15 cm, wet method dress post) on, 50 mL eluting add water, discard water liquid, use again ethanol 100 mL eluting, collect eluent, be evaporated near dry, residue dissolves with acetonitrile water (10:90) mixed solution, be transferred in 10 mL measuring bottles, add acetonitrile water (10: 90) mixed solution and be diluted to scale, shake up and get final product
Chromatographic column: Agilent ZORBAX DB-C18 (4. 6mm × 250mm, 5m); Mobile phase: acetonitrile: 0. 04% phosphoric acid (12.5:87.5); Detect wavelength: 280 nm; Flow velocity: 1. 0 mL/min; Column temperature: 30 DEG C; Sample size: 20 μ L
Three parts of working samples, epicatechin content is respectively: 215 μ g/bags, 225 μ g/bags, 195 μ g/bags.
The wild buttocks tail of 1-deoxidation mycin is measured: the chromatographic column of (1-D N J) assay: Agilent ZORBAX DB-C18 (mm × 250mm, 5m), mobile phase (acetonitrile)-0.1% acetic acid)=3 6: 64; Detect wavelength 254n m, flow velocity 1. 0m L/m i n, sample size 20 μ L.
Three parts of working samples, the mould cellulose content of the wild buttocks tail of 1-deoxidation is respectively: 75 μ g/bags, 95 μ g/bags, 115 μ g/bags.
Claims (4)
1. treat the Chinese medicine composition of diabetes complicated pneumonia for one kind, formed by effective ingredient and pharmaceutically acceptable carrier, it is characterized in that: described effective ingredient is to come from: one has alpha-glucosidase inhibiting medical herb position and Rhizoma Fagopyri Dibotryis composition, described in there is the inhibiting medical herb of alpha-glucosidase position and comprise: Ramulus Mori, Cortex Mori extract one or more.
2. a kind of Chinese medicine composition for the treatment of diabetes complicated pneumonia according to claim 1, is characterized in that: described have the inhibiting medical herb of an alpha-glucosidase position, and the Cortex Mori total alkaloid content of Cortex Mori extract is 10% 40%.
3. a kind of Chinese medicine composition for the treatment of diabetes complicated pneumonia according to claim 1, is characterized in that: in the preparation of said composition, contain the wild buttocks tail of epicatechin and 1-deoxidation mycin simultaneously.
4. as a kind of Chinese medicine composition for the treatment of diabetes complicated pneumonia of any one in claim 1～2 is treated the application in medicine for treating diabetic nephropathy in preparation.
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