CN102319299B - Pharmaceutical composition for treating chronic renal failure and preparation method thereof - Google Patents
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Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention discloses a pharmaceutical composition for treating chronic renal failure and a preparation method thereof, and is characterized in that the pharmaceutical composition comprises the following raw material herbs: 90-180 parts of herba epimedii by weight, 10-40 parts of cordyceps sinensis by weight, 90-180 parts of glossy privet fruit by weight, 10-40 parts of red ginseng by weight, 160-250 parts of astragalus membranaceus by weight, 10-40 parts of schisandra chinensis by weight, 300-500 parts of salvia miltiorrhiza by weight, 10-40 parts of rheum officinale by weight, and 20-50 part of mirabilite by weight. The medicament of the invention is prepared based on clinical experience of several years, employs the treatment principle of reinforcing spleen and kidney, protecting heart and generating blood, relieving vomiting and dysuria, grasps the physiological characteristics and the interdependence of the three organs of heart, spleen and kidney, and greatly emphasizes the effect of heart protection; clinical research results also demonstrate that heart protection does contribute to the improvement of the prognosis of CRF; by treating with the pharmaceutical composition of the invention, the renal functions (Ccr, Scr, BUN) are improved, and the Ccr and Scr are quite significantly different by statistical treatment.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, be specifically related to a kind of pharmaceutical composition for the treatment of chronic renal failure and preparation method thereof.
Background technology
Chronic renal failure (CRF) is a kind of commonly encountered diseases, frequently-occurring disease, owing to there is no at present the effective measures of control primary disease, so that many patient's protracteds course of disease, finally develop into Uraemia in telophase, seriously endangering patient's health and lives safety.Primary disease Chinese medical discrimination be take spleen deficiency of kidney-QI as main, due to Cardiovascular Damage also very common clinically, and be usually to cause CRF main causes of death.
Summary of the invention
The invention provides a kind of pharmaceutical composition for the treatment of chronic renal failure and preparation method thereof.The present invention seeks to be achieved through the following technical solutions:
Pharmaceutical composition crude drug of the present invention consists of:
Pharmaceutical composition crude drug composition of the present invention is preferably:
Pharmaceutical composition crude drug composition of the present invention is preferably:
Pharmaceutical composition crude drug composition of the present invention is preferably:
The preparation method of pharmaceutical composition of the present invention is:
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 1-3 time, each 1-2 hour, and collecting decoction, filters, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 at 50 ℃, adds Cordyceps fine powder, mixes; According to common process, add conventional adjuvant to make the mixture of clinical acceptance, concentrated pill, capsule, drop pill, granule, tablet, pill, soft capsule, slow releasing agent, oral liquid or ejection preparation.
Herba Epimedii of the present invention is processed with honey Herba Epimedii.
Medicine of the present invention is that long-pending clinical experience prescription for many years forms, take invigorating spleen and kidney, protect the heart being responsible for production of blood, open lattice and be open to the custom as the rule for the treatment of, caught heart spleen kidney three dirty physiological propertys and mutual root relation, on the basis of benefiting vital QI and blood, assistant is asked it slowly with the method that opens lattice and be open to the custom, and makes this difficulty heavily demonstrate,prove and be made a connection.Meanwhile, attach great importance to the effect of " guarantor's heart ", to scheme " main bright lower peace ", " full twelve interior organs is healthy for blood vessels ".This feature in prescription legislation that is medicine of the present invention as the medicine for the treatment of CRF is also the key factor that obtains good efficacy.Clinical research result also confirms, focuses on protecting the prognosis that the heart contributes to improve CRF really.
Following experimental example and embodiment are used for further illustrating but are not limited to the present invention.
Experimental example 1: the clinical research of the present invention's (embodiment 1 preparation) medicine composite for curing 48 routine chronic renal failures
Physical data:
Selection meets chronic renal failure diagnostic criteria, renal function by stages at II more than the phase, and Chinese medical discrimination belongs to spleen kidney qi (sun) deficiency syndrome, and the course of disease surpasses 6 months and gets rid of reversible factors person as observing case.Patient is divided into treatment group and matched group at random, and number of cases is respectively 48 and 30.10 examples of being in hospital in treatment group patient, outpatient service 38 examples; Male's 28 examples, women's 20 examples, age 26-65 year, average 49.90 ± 12.70.8 examples of being in hospital in matched group patient, outpatient service 22 examples, male's 18 examples, women's 12 examples, age 27-64 year, average 47.40 ± 11.63, the course of disease is the shortest 9 months, the longest by 22, average 5.29 ± 5.11 years.Two groups of ordinary circumstances are learned by statistics and are processed relatively, and there was no significant difference, has comparability.
Observational technique:
1, Therapeutic Method treatment group gives pharmaceutical composition of the present invention, by Xiyuan Hospital, Chinese Medicine Academy of China's experiment pharmaceutical factory, is produced, and every bag containing 15 grams of crude drugs, each 2 bags, every bu 2 times.Matched group gives NIAODUQING electuary, and by Guangzhou, pharmaceutical factory of Nanfang Hospital produces, and each 1 bag, every day 4 times.Two groups all adopt diet control and the conventional symptomatic treatment of doctor trained in Western medicine, as corrected acidosis and water, electrolyte disturbance, if there is the infected, give anti-infective therapy; Hyperpietic, gives depressor treatment etc.Within 2 months, be 1 course for the treatment of, all patients all treated for 2 courses for the treatment of.
2, observation index: tcm symptom and sign, renal function (Ccr, Scr, BUN), blood fat (TG, TC), Endothelin (ET), parathyroid hormone (PTH) and ultrasoundcardiogram.
3, statistical method: enumeration data X 2 test, measurement data adopts t check, and ranked data adopt Ridit check
Result:
1, curative effect determinate standard is effective: A, clinical symptom relief or disappearance; B, endogenous creatinine clearance rate increase >=30%; C, serum creatinine reduce >=30%; Effective: A, clinical symptom relief or disappearance; B, endogenous creatinine clearance rate >=20%; C, serum creatinine reduce >=20%; Invalid: clinical manifestation and lab testing are all not improved or deterioration person.
2, clinical curative effect analysis: effective 14 examples for the treatment of group (29.17), effective 23 examples (47.92%), invalid 11 examples (22.92%), total effective rate is 77.08%.Effective 4 examples of matched group (13.33%), effective 17 examples (56.67%), no effect 9 (30%), total effective rate is 70%.Two groups of curative effects are learned by statistics and are processed relatively, there was no significant difference, and obvious effective rate is learned processing by statistics, u=59.14, P < 0.01, has significant differences.
3, the improvement situation comparison of two groups of cardinal symptoms: pharmaceutical composition of the present invention is better than NIAODUQING electuary to the improvement that patient's fatigue and weakness, waist soreness, nocturia increase, cardiopalmus is seized with terror, learns and processes by statistics, and P < 0.05, has significant difference.
4, the variation comparison of renal function before and after two groups of treatments, in Table 1.
The situation of change of renal function before and after table 1 liang group treatment
| Group | Number of cases | Ccr(ml/min) | Scr(umol/l) | BUN(mmol/l) |
| Treatment group | ||||
| Before treatment | 48 | 10.77±9.44 | 555.04±318.80 | 26.10±15.6 |
| After treatment | 48 | 18.46±15.84△△ | 420.74±239.19△ | 21.96±13.84 |
| Matched group | ||||
| Before treatment | 30 | 13.33±9.10 | 430.35±234.63 | 23.91±12.02 |
| After treatment | 30 | 14.12±13.02 | 400.43±168.99 | 27.86±18.24 |
With before treatment relatively: △ P < 0.05 △ △ P < 0.01 time with.
From table 1, renal function after medicine composite for curing of the present invention (Ccr, Scr, BUN) is all improved, and learns and processes by statistics, and before and after treatment, Ccr, Scr have significant difference (P < 0.01).NIAODUQING electuary group renal function improves not obvious.Other two groups of Ccr, Scr, BUN improve there was no significant difference (P < 0.01).
5, the situation of change of hemoglobin and plasma protein before and after two groups of treatments, in Table 2.
The situation of change of hemoglobin and plasma protein before and after table 2 liang group treatment
| Group | Number of cases | Ccr(ml/min) | Scr(umol/l) | BUN(mmol/l) |
| Treatment group | ||||
| Before treatment | 48 | 87.74±25.43 | 41.67±6.53 | 66.68±8.35 |
| After treatment | 48 | 98.02±25.03△ | 42.97±5.78 | 67.59±12.25 |
| Matched group | ||||
| Before treatment | 30 | 87.93±32.49 | 43.04±3.4 | 69.37±5.026 |
| After treatment | 30 | 94.23±26.47 | 42.52±3.5 | 69.72±7.14 |
From table 2, pharmaceutical composition of the present invention can significantly improve the renal anemia that chronic renal failure causes, suitable with the effect of NIAODUQING electuary group.
6, Blood Lipid situation comparison before and after two groups of treatments, in Table 3.
The impact of table 3 pharmaceutical composition of the present invention on blood fat
| Number of cases | Before treatment | After treatment | |
| Cholesterol (mmol/L) | 42 | 5.21±1.81 | 4.08±1.84△△ |
| Triglyceride (mmol/L) | 42 | 2.13±1.19 | 1.64±0.99△ |
From table 3, pharmaceutical composition of the present invention has remarkable effect for reducing blood fat, and prompting the present invention can correct metabolism disorder of blood lipid, not only can delay CRF, can also prevent and treat the generation of cardiovascular complication.
7, the impact of pharmaceutical composition of the present invention on Endothelin (ET) and parathyroid hormone (PTH): in Table 4.
The impact of table 4 pharmaceutical composition of the present invention on Endothelin and parathyroid hormone
| Number of cases | Before treatment | After treatment | |
| ET(pg/ml) | 11 | 80.56±40.23 | 50.67±16.18△ |
| PTH(pg/ml) | 11 | 262.18±105.34 | 156.51±119.21△ |
From table 4, pharmaceutical composition of the present invention can obviously reduce CRF and cause that ET raises and PTH raises, thereby plays the protective effect to heart kidney.
8, the impact of pharmaceutical composition of the present invention on heart damage: in Table 5.
The impact of table 5 pharmaceutical composition of the present invention on heart
| Project | Number of cases | Before treatment | After treatment | P value |
| Left ventricle anteroposterior diameter | 11 | 48.67±2.83 | 48.87±3.18 | ＞0.05 |
| Left ventricle spacer thickness | 11 | 8.67±1.23 | 8.22±0.44 | ＞0.05 |
| LVEF | 11 | 70.22±11.21 | 69.22±11.64 | ＞0.05 |
| Left ventricular posterior wall thickness | 11 | 7.61±0.82 | 8.11±1.27 | ＞0.05 |
| Mevf | 11 | 9.24±2.32 | 8.55±2.29 | ＞0.05 |
| EPSS | 11 | 4.64±2.36 | 6.25±2.63 | ＞0.05 |
| Left atrium diameter l | 11 | 32.11±3.18 | 31.67±1.80 | ＞0.05 |
| Chamber anteroposterior diameter again | 11 | 17.63±4.21 | 17.63±3.82 | ＞0.05 |
| Two class lobe peak velocities | 11 | 0.70±0.22 | 0.63±0.17 | ＞0.05 |
| Bicuspid valve A peak flow velocity | 11 | 0.74±0.21 | 0.77±0.21 | ＞0.05 |
| Bicuspid valve A/E value | 11 | 1.09±0.47 | 1.25±0.32 | ＞0.05 |
| Tricuspid valve peak velocity | 11 | 0.52±0.08 | 0.58±0.16 | ＞0.05 |
| Aorta peak velocity | 11 | 1.04±0.18 | 1.13±0.37 | ＞0.05 |
| Pulmonary artery peak velocity | 11 | 0.88±0.16 | 0.95±0.19 | ＞0.05 |
| Aortic valve opening extent | 11 | 18.78±1.64 | 18.67±1.32 | ＞0.05 |
| Aortic valve internal diameter | 11 | 20.11±1.90 | 20.56±1.42 | ＞0.05 |
| Aortic sinus portion anteroposterior diameter | 11 | 31.00±3.35 | 31.00±2.78 | ＞0.05 |
From table 5; before and after medicine composite for curing group patient's of the present invention echocardiography indices treatment, without significance, change; show not increase the weight of at period in a medicine heart damage, thereby the heart damage that prompting pharmaceutical composition of the present invention causes CRF has certain protective effect.
Experimental example 2: the present invention's (embodiment 1 preparation) treatment and the mechanism thereof of pharmaceutical composition to rat 5/6 nephrectomy chronic renal failure (CRF)
Materials and methods
(1) laboratory animal: select 70 of male Wister rat, body weight 230-270g, 309 animal housing of hospital of PLA provide.Purchase people rat all negative through normal raising in a week, survey urine protein, side's row operation.
(2) experimental drug: the present invention's (embodiment 1 preparation) pharmaceutical composition, the Drug Manufacturing Room of Xiyuan Hospital, Chinese Medicine Academy of China provide.NIAODUQING pharmaceutical composition of the present invention, Guangzhou Kang Chen pharmaceutical factory (No.1 Military Medical Univ.).Lotensin, Beijing vapour Ba-Jia Ji pharmaceutical Co. Ltd.
(3) modeling method: experiment chronic renal failure model adopts Platt R method (22), select 10% concentration chloral hydrate, press the anesthesia of 0.3ml/100g body weight, through lumbar injection, after anaesthetizing, be fixed on minor operation plate rat is prostrate, Jian Jing ridge district portion chaeta, iodine tincture, ethanol is now sterilization often, in sterile working, ridge skin incision 3.0cm, downward deep 2.0cm on Zai Xiangjinzuo kidney district dorsal muscles, with anodontia (smoothly) clamper, draw out left kidney, in separation, lower fatty renal capsule, from upper, declivity cuts off cortex part (should not cut brokenly renal pelvis), apply fast gelatin foam hemostasis, remove hemorrhage after, put and return abdominal cavity, sew up dorsal muscles, kidney district is deep to the right again, with said method, take out right kidney, separated the two poles of the earth fatty renal capsule, with mosquito forceps, clamp renal artery, in the renal artery near-end ligation kidney base of a fruit, along mosquito forceps top, wipe out kidney again, unclamp mosquito forceps, put and return abdominal cavity, be taken up in order of priority and sew up dorsal muscles and skin, wound iodine tincture, alcohol disinfecting, kidney 75 approximately percent left and right is excised in operation altogether.
(4) grouping and administration: after operation, guaranteeing under conditions of water drinking, common cubed feed (crude protein quantity=22%) is fed three weeks, after performing the operation two weeks, randomly draw normal group and modeling group, measure respectively serum creatinine (scr) and hematuria element (Bun), modeling group and normal group comparison, modeling group rat creatinine, hematuria element obviously raises, and each group asks and make significance test have significant difference (P < 0.05).Again according to random process method, divide five groups afterwards: 12 of NIAODUQING pharmaceutical composition groups of the present invention, every day, gavage took pharmaceutical composition 7.14 * 10-3 body weight of the present invention every day (by 20 times/kg of adult's consumption body weight).12 of medicine composite for curing groups of the present invention, every day, gavage took pharmaceutical composition 0.02g/g of the present invention every day (by 20 times/kg of the consumption body weight of being grown up every day.12 of lotensin treatment groups, every day, gavage took 7.143 * 10-4mg/g body weight every day (by 20 times/kg of the consumption body weight of being grown up every day).12 of pathology matched groups, every day, gavage took cold water, and the amount of gavaging is 2ml/ day.10 under equal conditions row sham-operations are Normal group.To postoperative the 3rd week, start each treatment group and the pathologic group high protein high salt diet (crude protein content is=50%, contains Sal=5%, by Jiujiang feed factory autocracy) of feeding.
(5) mensuration of blood pressure: treat to measure respectively for the 8th week and 12 weeks and respectively organize rat tail arterial blood pressure, with Blood pressure meter for Rat model RBP-1, China-JapanFriendship Hospital survey meter of blood pressure.
(6) collection of specimens: the above-mentioned rat successive administration to ten of respectively organizing starts kill animals after two weeks and collects specimen.Sacrifice of animal was plucked in the past eyeball and was got blood, after do the external perfusion experiment of heart, take out kidney simultaneously fast, weigh, kidney is divided into 2 parts, does light microscopic, electron microscopic examination.Heart is done after external perfusion experiment, rapid weighing, and heart is divided into 3 parts, does light microscopic, Electronic Speculum and puts quick-freezing in liquid nitrogen, preserves.
(7) observation item:
1, overview: observe and respectively organize rat diet, defecation, expression, Mao Ze, diet, mobility, body weight, survival rate etc.
2, blood biochemical analysis
Serum creatinine: respectively at treating 4th week, getting blood and finally pluck eye with eye socket for eight weeks, 12 weeks
Ball is got blood.
Blood urea nitrogen
Hematochrome
Serum calcium
Serum paraoxonase
Serum albumin
Total serum protein
Serum total cholesterol
Serum triglycerides
Serum LDL .Chol
Serum hdl .Chol
Above-mentioned hematochrome: adopt Sysmex F-820 and F-270 (Japan manufactures) automatic analyzer to measure, other biochemical indicators all adopt Italy to manufacture AMS photo-Analyzer FT-2 biochemical instruments and measure.
Urinate 24 hours protein determinations, treat and rat was positioned over respectively in metabolic cage in the 4th, eight, 12 weeks, collect twenty-four-hour urine amount, adopt NHITACHI 7150Automatic Analyzer (Japan manufactures) to measure.
3, the mensuration β 2-mG RIA KIT IMK (Code) of blood, urine β 2 one microglobulins numbering 416, and Beijing China Atomic Energy Science Research Institute produces, the full-automatic Y calculating instrument of FF620G, and Beijing Nuclear Instrument Factory produces.
4, left compartment muscle Endothelin and atrial natriuretic peptide are measured:
(1) Endothelin: Endothelin RIA Kit East Asia immunological technique institute, China, Beijing (95) defend No. R-68, the accurate word of medicine '
(2) atrial natriuretic peptide: ANFR1A Kit China Atomic Energy Science Research Institute, Beijing, defends No. R-15 above-mentioned LKB of adopting 1272Clinigamma Automatic Gamma Counter of the accurate word of medicine, (Sweden's system) analyzer.
5, the heart, nephridial tissue pathological examination
The heart, nephridial tissue are fixed with 20% formalin, paraffin embedding, and film-making, HE, PAM-HE dyeing, om observation, a little tissue collecting makes electron microscopy study.
6, statistical disposition: each achievement data all represents with mean ± standard deviation (x ± SD), measurement data one factor analysis of variance between group.
Result
(1) impact on general status
Overall health of patients: all dead 12 survival rates 82.86% of second day after operation to two, the cause of the death how anxious renal failure, massive hemorrhage and infection.After the 3rd day, animal situation is more steady, and the cause of the death is mainly edema, chronic renal failure and gavage die of asphyxiation (because animal temper becomes impetuous).Outward appearance: the present invention's (embodiment 1 preparation) pharmaceutical composition group, lotensin group rat hair color gloss, flexible movements, and NIAODUQING group pathologic group, hair color is withered and yellow without pool gradually, and mobility is poor and temper is impetuous.
Diet aspect: modeling rat appetite was all on a declining curve in postoperative one week.Two weeks start, it is cumulative that each organizes rat appetite, by the 3rd week because starting to feed high salt high protein feed, each organizes rat amount of drinking water increases, in Table 6, normal group < the present invention (embodiment 1 preparation) pharmaceutical composition group < NIAODUQING group < lotensin group < pathologic group, urine amount aspect, in Table 7, each group also increases to some extent, pathologic group > lotensin group > NIAODUQING group > the present invention (embodiment 1 preparation) pharmaceutical composition group, appetite aspect, each is organized compared with normal group and reduces, but body weight increases, in Table 8, through dissecting dead rat, all there is edema, as ascites, pathological manifestations resembles similar in appearance to the spleen deficiency of kidney-QI of the traditional Chinese medical science.
Urine protein aspect: postoperative one week, modeling rat is visible urine protein all, qualitative ±～+++ not etc.After GP TH, the 4th, eight, 12 weeks, twenty-four-hour urine albumen quantitatively all lower than 9 of the following expression of pathologic group.
Table 6 is respectively organized rat amount of drinking water comparison in 24 hours
mI/24h
※ and pathologic group be P < 0.05 relatively
※ ※ and pathologic group be P < 0.01 relatively
Table 7 is respectively organized rat twenty-four-hour urine amount
mI/24h
※ and pathologic group be P < 0.05 relatively
※ ※ and pathologic group be P < 0.01 relatively
Table 8 is respectively organized the variation of rat body weight
gram
※ and pathologic group compare P < 0.05 △ △ and normal group compares P < 0.01
※ ※ and pathologic group compare P < 0.01 △ and normal group compares P < 0.05
The table 9 twenty-four-hour urine protein quantification of four or eight ten two weeks
mg/24h
※ and pathologic group relatively have significant difference P < 0.05
※ ※ and pathologic group relatively have significant differences P < 0.01
(2) kidney wet weight and body weight ratio change in Table 10
Table 10 is respectively organized kidney weight in wet base and the comparison of body weight ratio after 12 weeks
※ ※ and pathologic group relatively have significant differences P < 0.001
★ ★ and pharmaceutical composition group of the present invention relatively have significant differences P < 0.01
★ and pharmaceutical composition group of the present invention relatively have significant difference P < 0.05
(3) impact on blood urea nitrogen and creatinine
Pathologic group blood urea nitrogen and creatinine all raise, all there is significant difference (P < 0.01) with normal group, the present invention's (embodiment 1 preparation) pharmaceutical composition group, NIAODUQING group, lotensin group, this explanation the present invention is improved renal function, but pharmaceutical composition group of the present invention and lotensin group be no significant difference (P > 0.05) more, aspect creatinine, pharmaceutical composition group suppression ratio NIAODUQING of the present invention many 17.31%.And statistically (there were significant differences for P<0.05>, illustrates that pharmaceutical composition group of the present invention improves renal function effect and be better than NIAODUQING, and similar to lotensin (P > 0.05).(in Table 11-13)
The variation of table 11 modeling time and creatinine
(mmol/L)
※ ※ and pathologic group be P < 0.01 relatively
★ ★ and pharmaceutical composition group of the present invention be P < 0.01 relatively
The variation of table 12 modeling time and BUN
(mmol/L)
※ and pathologic group be P < 0.05 relatively
★ ★ and pharmaceutical composition group of the present invention be P < 0.01 relatively
Table 13 is respectively organized the comparison of blood urea nitrogen and creatinine after 12 weeks
※ ※ and pathologic group be P < 0.01 relatively
★ ★ and pharmaceutical composition group of the present invention be P < 0.05 relatively
(4) impact on hemoglobin
NIAODUQING, pharmaceutical composition of the present invention, a lotensin group hemoglobin and pathologic group be significantly increased (P < 0.01) in this test, pharmaceutical composition group of the present invention is higher than NIAODUQING group, and be better than lotensin group (P < 0.05), illustrate that the present invention has hemopoietic function, contribute to improve the quality of living, (in Table 14).
Table 14 is the impact on hemoglobin after 12 weeks
※ ※ and pathologic group be P < 0.01 relatively
★ ★ and pharmaceutical composition group of the present invention be P < 0.05 relatively
(5) impact on serum albumin and total protein
Aspect raising serum albumin, pharmaceutical composition group of the present invention and NIAODUQING group have highly significant effect (P < 0.01), but lotensin does not have this effect, for total protein aspect, pharmaceutical composition of the present invention is better than NIAODUQING (P < 0.05) and lotensin group (P < 0.01), in Table 15.
Table 15 is respectively organized the comparison of serum albumin and total protein after 12 weeks
※ and pathologic group compare P < 0.05 ★ and pharmaceutical composition group of the present invention compares P < 0.05
※ ※ and pathologic group compare P < 0.01 ★ ★ and pharmaceutical composition group of the present invention compares P < 0.01
(6) impact on T-CHOL and triglyceride
Pathologic group T-CHOL increases extremely, and each medication group T-CHOL is lower than pathologic group respectively, and has statistically remarkable meaning, and between three groups, pharmaceutical composition group T-CHOL of the present invention is minimum.
Aspect triglyceride, pharmaceutical composition group of the present invention, effect for reducing fat is (P < 0.01) very obviously, is secondly NIAODUQING (P < 0.05), and lotensin group is not obvious, in Table 16.
Table 16 is respectively organized the comparison of T-CHOL and triglyceride after 12 weeks
★ ★ and pathologic group be P < 0.01 relatively
(7) to B
2the impact of-microglobulin
This experimental result, pharmaceutical composition of the present invention and NIAODUQING have obvious reduction B2 microglobulin, lotensin is effective (P < 0.05) also, for urine B2 microglobulin aspect, pharmaceutical composition of the present invention is better than NIAODUQING, and than lotensin significantly (P < 0.05), in Table 17.
Table 17 is respectively organized the comparison of B2M after 12 weeks
※ and pathologic group compare P < 0.05 ★ and pharmaceutical composition group of the present invention compares P < 0.05
※ ※ and pathologic group be P < 0.01 relatively
(8) impact with high density lipoprotein (HDL) on low density lipoprotein, LDL (LDL)
In experimental result, in Table 18, showing that pharmaceutical composition of the present invention has very significantly reduces LDL (P < 0.01), be secondly lotensin, and NIAODUQING is not obvious, for improving HDL, in three groups of medicines, pharmaceutical composition of the present invention is the highest, and for treatment of vascular, sclerosis has effect to this explanation Herba mesonae chinensis, contribute to prevent sclerosis of blood vessels effect, contribute to prevent complicated with cardiovascular sick.
Table 18 is respectively organized the comparison of LDL and HDL after 12 weeks
※ ※ and pathologic group be P < 0.05 relatively
※ ※ and pathologic group be P < 0.01 relatively
(9) impact on blood calcium and serium inorganic phosphorus
CRF has calcium, phosphorus metabolism obstacle often, especially hemodialysis patients has hypercalcemia and hyperphosphatemia, just there is high calcium high phosphorus in this experiment, doctor trained in Western medicine is applied low calcium dialysis treatment and is added the oral phosphorus agent of falling, and in this test, pharmaceutical composition of the present invention has the phosphorus of falling effect (P < 0.05), in Table 19.Fall phosphorus and can prevent the damage of cardiac muscle.
Table 19 is respectively organized the comparison of blood calcium and serium inorganic phosphorus after 12 weeks
※ ※ and pathologic group be P < 0.01 relatively
※ ※ and pathologic group be P < 0.05 relatively
(10) impact with Endothelin (ET) on atrial natriuretic peptide (ANF)
During CRF, miopragia is moved in the ANF specific receptor in kidney and deactivation, and plasma ANF raises, but the effects such as its diuresis and expansion blood vessel disappear.In addition ET level obviously raise and with blood BUN, Cr is proportionate and is.Experimental result, in Table 20, pharmaceutical composition group of the present invention and lotensin group are not obvious, and NIAODUQING group raises very obvious, for tri-groups of ET, all have reducing effect (P < 0.01), and pharmaceutical composition group of the present invention is better than NIAODUQING group and the equivalence of lotensin group.
The comparison of atrial natriuretic peptide and Endothelin is respectively organized in table 20 treatment after 12 weeks
※ and pathologic group compare P < 0.05 ★ and pharmaceutical composition group of the present invention compares P < 0.01
※ ※ and pathologic group be P < 0.01 relatively
(11) impact on blood pressure
CRF is often with hypertension, and hypertension not only increases the weight of the infringement of renal function but also affects cardiac function, so control blood pressure, is the important step that delays and treat chronic renal failure, is also one of cardioprotection means.Experimental result shows 8 weeks, 12 weeks, all have hypotensive effect, in Table 21.
Table 21 is respectively organized after eight weeks the blood pressure comparison rear in 12 weeks
※ and pathologic group compare P < 0.05 ★ and pharmaceutical composition group of the present invention compares P < 0.05
※ ※ and pathologic group be P < 0.01 relatively
The Histomorphological of (12) Herba mesonae chinensis Chongji for Treatment chronic renal failure experimentation
Instrument: paraffin slicing machine, Japan, ERMA; Automatic tissue dehydration apparatus, Hubei China Xiaogan Electronic Instruments Plant, TS-12E type; Microscope, Japan, OLYPUS, BH-2 type.
Method: get kidney after zootomy and put into formalin solution and fix, dehydration after drawing materials, paraffin
Embedding, film-making, HE, PAM-HE dyeing, om observation.
Result:
Normal group: on kidney, ball and renal tubules structure are normal
Pathologic group: glomerule severe proliferation of mesangial cells and extracellular matrix increase, part GCBM is segmental fracture and segmental necrosis.The whole interior visible albumen exudate of capsule ball, locates and has a diffuse crescent formation; Part glomerule is segmented sclerosis; Indivedual glomerule are full bead sclerosis.In glomerule, erythrocyte becomes silted up and collects, and has the visible microthrombusis in place.Part renal tubules is atrophy sexual intercourse; Indivedual renal tubules are the protein cast that in gangrenosum acne variation, tube chamber, more or less as seen.Kidney interstitial has place to be fibrosis, and has lymphocytic infiltration, asks small artery wall thickening in matter, has hardening phenomenon.
Of the present invention group: most glomerule are slight mesentery hypertrophy, sometimes can see the glomerule of structure normal.A small amount of glomerule is slight segmented sclerosis, and indivedual visible capillary basement membranes of glomerule have phenomenon of rupture, but has no the glomerule of full bead sclerosis.' the visible a small amount of protein cast of urinary cast intracavity is with a little fat vacuole.
NIAODUQING group: most of glomerule is moderate mesentery hypertrophy, the erythrocyte of visible bunchiness string for stringing up cash in ancient times money shape in blood capillary, the visible capillary basement membrane of part glomerule has phenomenon of rupture, and part glomerule has slight sclerosis.Glomerule balloon wall thickens some and is division.Part renal tubular epithelial tissue is downright bad variation, has a plurality of protein casts in tube chamber, has fibrosis in interstitial.
Lotensin group: most of glomerule is moderate mesentery hypertrophy, and has neutrophilic infiltration.Some fracture of GCBM, and visible " double track " changes.Glomerular capillary intracavity can a plurality of microthrombusiss of party, and indivedual glomerule are downright bad, and in balloon cavity, visible albumen exudate, has a plurality of bulky protein casts in renal tubules, and interstitial has cell infiltration.
Under 10 * 10 times of mirrors, each group is observed respectively 5 * 5 visuals field, counting glomerule, and the processing that takes statistics, and result is as table 22
Table 22 sclerosis rate
According to above-mentioned showing, pathologic group hardening ratio is for the highest by 29.09%, secondly for lotensin group is 7.59%, and NIAODUQING group and Herba mesonae chinensis electuary group are minimum, be respectively 0.58% and 0.64%, through Ridit, check, the clear pathological changes of Herba mesonae chinensis electuary group and NIAODUQING is all very significantly lighter than pathologic group P < 0.01, and two groups are also significantly better than lotensin group (P < 0.05), illustrate that we have the sclerosis that reduces glomerule, the effect of control renal failure.
Tectology is discussed
Histomorphological result shows, Herba mesonae chinensis electuary has the sclerosis that alleviates glomerule, and more normal glomerule as seen in tissue slice, there is no discarded glomerule and diffuse crescent formation, sclerosis number through technology glomerule is done statistical disposition, we's hardening ratio is very significantly low (P < 0.01) than case group, and significantly lower than lotensin group (P < 0.05), illustrates that we have the effect of control glomerular sclerosis.
Experimental example 3: the experimentation of the present invention's (embodiment 1 preparation) pharmaceutical composition cardioprotection function
Materials and methods
One, material:
1, animal: the Rat Heart that is taken at 5/6 nephrectomy chronic renal failure.
2, medicine and reagent:
NaCI, KCL, KH2PO4, MgSO4,7H2o, cacI2, NaHCO3 glucose, K2HPO4, is provided by Beijing chemical reagent two factories, Red Star chemical plant, Beijing, China Drug Co.'s Beijing purchasing and supply station etc.
Heparin, China Drug Co.'s Beijing purchasing and supply station.
3, dosing: distilled water is all used in dosing.
(1) KH liquid: experiment preparation on the same day.Form: NaCl, 118.ommol/L, 4.7mmol/L, KH2PO4,0.93mmol/L, MgSO4 7H2o, 1.2mmol/L, caCI2,1.5mm01/L, NaHc03,250mmol/L, glucose, 11.0mmol/L, pH7.30-7.40.
4, Endothelin is put and is exempted from medicine box: (95) defend immunological technique institute BeiJing, China, mono-No. 68 East Asia of the accurate word R of medicine
5, instrument:
Channel polygraph, RM6000, Japanese photoelectricity
Thermostatic water-circulator bath device, 501 types, Shanghai City Shanghai County the second hardware factory
Multifunctional heart program stimulation instrument, FD-1A type, state-run Taizhou Electronic Instruments Plant
Electronic analytical balance, MPl20-1 type, Shanghai Second Balance Factory
Electronic analytical balance, ER mono-182A type, Japanese Shimadzu
Digital ph, PHS mono-3C type, Fan Long Instrument Ltd.
Pressure transducer .TP mono-200T, Japanese photoelectricity
Full-automatic r calculating instrument, FF620G, Beijing Nuclear Instrument Factory produces.
Two, method:
1, grouping: animal grouping is according to the experiment grouping of above-mentioned 5/6 nephrectomy rat, be divided into 9 of (1) normal group, 8 of (2) pathologic group, 7 of (3) NIAODUQING groups, (4) 10 of the present invention (embodiment 1 preparation) pharmaceutical composition groups, 8 of (5) lotensin groups.
2, experimental implementation: 5/6 nephrectomy chronic renal failure rat, after eyeball blood-letting, is opened thoracic cavity at once, clip heart, stops fighting with 4 ℃ of cold NS rapidly, after pruning, aortic cannulation is installed, and carries out the perfusion of Langendorff device.Pressure is due to 60mmHg, and infusion liquid is used 37.C constant temperature KHB, fills with 95%02 and 5%CO2.Ventricle endosphere is installed, and topping up, makes left ventricular end diastolic presssure (LVEDP). due to 10mmHg.Stablize 10 ' after, measure arteria coronaria charge (CF), record parameters of left ventricular function.If heart rate is less than 300 beats/min, use heart rate actuator by heart rate due to 300 beats/min, after 3min, measure once again parameters of left ventricular function, in pouring into again 20 ', 30 ' record parameters of left ventricular function, and measure CF.
3, instrument condition:
CarrierAmplifer，AP-610G：GAIN FACTOR：6.35，SEN：50mmHg/DIV，Direct，Speed：10mm/sec.
Differentiator, ED-600G:TIME CONST:0.5msec, HICUT:15Hz, SEN:7.7, Clipper: off for amplitude hour, when large with "+" or " one ".
Multifunctional heart program stimulation instrument: S1 is synchronous, " S1 ", cycle: 200ms, Sl output, " directly going out ", " intracardiac ", amplitude 2-3V
4, index:
(1) parameters of left ventricular function: left chamber maximum collapse is pressed (LVPSP), heart rate (HR), the maximum rate of change (± DP/DTmax) of intraventricular pressure.Adjust ventricle endosphere filling amount, when LVEDP is scheduled to 10mmHg, measure each value.Heart rate and intraventricular pressure change the xHR of product (RPP)=(LVPSP.LVEDP);
(2) CF:LVEDP measures this value when 10mmHg;
(3) ventricular muscles weight in wet base: perfusion is taken off heart after finishing immediately, cuts off atrium along coronary sulcus, wipes away dryly with filter paper, take weight in wet base.
(4) ventricular muscles histopathological examination: ventricular muscles claims after weight in wet base, takes out two fritters.With 20% formalin normal saline solution, fix for one.Specimens paraffin embedding slices, does HE dyeing, and another piece is fixed with phosphate buffer glutaraldehyde, through conventional method, makes electron microscopic section.
(5) ventricular muscles Endothelin is measured:
1. ventricular muscles is claimed after weight in wet base freezingly rapidly, be stored in liquid nitrogen.
2. take out and be stored in the ventricular muscles in liquid nitrogen, the muscular tissue of the coring 100mg that weighs, puts as early as possible 1HAClml and mills, then in 100 ℃ of water-baths, boil 10 minutes, and homogenate, 4 ℃ of centrifugal 15min of 3000rpm, get at supernatant-20 ℃ and preserve, and Endothelin is measured the method for exempting from of putting that adopts.
5, statistical procedures: variable represents with X ± SD.Adopt non-matching students ' check.
Three, experimental result
(1) cardiac determination
1, heart rate situation: experimental result shows that the present invention (embodiment 1 preparation) pharmaceutical composition is to stablizing chronic kidney hypofunction rat heart rate and be better than NIAODUQING and pathologic group (P < 0.05) being better than lotensin, as following table 23.
Table 23 heart rate (HR): (beat/min)
※ and pathologic group be P < 0.05 relatively
※ ※ and pathologic group be P < 0.01 relatively
2, ventricular systolic function: press and the maximum rate of change situation of intraventricular pressure from left ventricle maximum collapse; the present invention's (embodiment 1 preparation) each treatment group of pharmaceutical composition group left ventricle maximum collapse pressure ratio is lower; prompting the present invention can reduce cardiac afterload, plays protection Myocardial Effects.For the rate of change of intraventricular pressure maximum, the present invention is also high than NIAODUQING group, illustrates that myocardial function damage is not heavy, as following table 24,25.
The left chamber of table 24 maximum collapse is pressed (LVPSP): mmHg
The maximum rate of change (+DP/DTmax) of table 25 intraventricular pressure: (mmHg/sec)
3, ventricular diastole function: from a DP/DTmax meansigma methods, the present invention (embodiment 1 preparation) pharmaceutical composition group is to improve ventricular diastole function aspects similar to lotensin effect, and NIAODUQING effect is the poorest, as shown in table 26 below.
The rate of change (DP/DTmax) of table 26 intraventricular pressure maximum: (mmHg/sec)
4, the impact on heart rate and intraventricular pressure variation product: from the overall situation of cardiac function, the average of the present invention's (embodiment 1 preparation) pharmaceutical composition group is lower than normal group, but all higher than other each groups. and the present invention's (embodiment 1 preparation) pharmaceutical composition group and NIAODUQING group variant (P < 0.05), as shown in table 27 below.
Table 27 heart rate and intraventricular pressure change product (RPP): (mmHg/sec)
※ and pathologic group be P < 0.05 relatively
(2) impact on coronary flow: the present invention as can be seen from Table 28 (embodiment 1 preparation) pharmaceutical composition is better than NIAODUQING group (P < 0.05) to improving coronary flow.
Table 28 coronary flow (CF) (ml/min)
(3) impact on myocardium weight in wet base and the variation of body weight ratio and ventricular muscles Endothelin (ET), in Table 29.
Experimental result shows. the present invention (embodiment 1 preparation) pharmaceutical composition all can reduce myocardial hypertrophy (P < 0.01) with lotensin, and the present invention's (embodiment 1 preparation) thus pharmaceutical composition can also obviously reduce the effect that myocardium interior ET. plays cardioprotection.
Myocardium weight in wet base respectively organized by table 29 and body weight ratio compares and myocardium chamber Endothelin (ET) compares
※ and pathologic group comparison (P < 0.05)
★ and the present invention (embodiment 1 preparation) pharmaceutical composition comparison (P < 0.05)
※ ※ and pathologic group comparison (P < 0.01)
Experimental example 4, the present invention's (the embodiment 1 preparation) impact of pharmaceutical composition on isolated culture neonatal rat myocardial cell
With the present invention's (embodiment 1 preparation) pharmaceutical composition aqueous solution (16g/kg/ day), give Wistar rat gavage, every day 1 time, continuous 10 days, after last administration 1 hour, eyeball was got blood, and centrifuging and taking serum, be placed in 56 ℃ of water bath 30min deactivation complements, 0.22 μ syringe needle filter filters, and is sub-packed in sterile vials, and-20 ℃ frozen standby.Normal rat serum is got blood with the normal Wistar white mouse of not medication with said method, prepares frozen standby.
Experimental example 5: the impact of Primary cultured myocardial cells Endotoxin Damage
Experiment minutes five groups, i.e. matched group, LPS (10ul/ml) group, LPS (100ul/ml) group, medicine serum 200ul/ml+LPS (100ul/ml) group, medicine serum 400ul/ml+LPS (100ul/ml) group.After above-mentioned grouping, test, and be determined as follows index: 1., muscle cell membrane Membranous lipid fluidity is 3. mtt assay cytoactive etc. of cytosolic free calcium concentration in cardiomyocyte 2..
Method: the cell suspension after packet transaction is splashed into respectively to 95 orifice plates and count approximately 4 * 10
5/ ml, 37 ℃, under 5% carbon dioxide, incubation, after the short time, adds 20ul/ hole MTT (5mg/ml is dissolved in PBS preparation), 37 ℃, under 5%-carbonoxide condition, train after 14h, abandon supernatant, add after the dimethyl sulphoxide solution (preparation of 20%SDS+10% dimethyl sulfoxide) in 150ul/ hole 37 ℃, 5% carbon dioxide lucifuge was hatched after 10 hours, measured its optical density value.This experimental applications DG3022 type enzyme-linked immunosorbent assay instrument (λ=570nm), every group of 10 holes, result is done statistical procedures.
Result
One, endotoxin is attacked the protective effect on the impact of myocardial cell activity and the present invention's (embodiment 1 preparation) pharmaceutical composition, as shown in following table 30
The comparison of mtt assay cytoactive between each group of table 30
Between group, compare:
G3：G4t＝6.9393P＜0.001※※
G3：G5t＝0.5217P＞0.5
From the cytoactive of upper table prompting medicine serum 200ul/ml+LPS (100ul/rnl) and matched group without statistical discrepancy; but with by LPs attack group, relatively have obvious rising separately; statistical disposition has significant differences (P < o01), illustrates that the present invention has protective effect to the activity of myocardial cell.
Two, the present invention (embodiment 1 preparation) pharmaceutical composition on the impact of cultivating myocardial cell LPS attack model membrane fluidity as table 31.
The comparison of cell membrane fluidity between each group of table 31
Between group, compare:
G3：G4t＝3.2879P＜0.02※※
G3：G5t＝3.3579P＜0.02※※
From upper table, point out two medicine serum groups all to improve cell membrane fluidity and there were significant differences (P < 0.02) with pathologic group.After myocardial cell under fire damages, cell membrane fluidity can reduce, as pathologic group.And treatment group is due to the protective effect of medicine, the mobility of its film does not reduce, and can maintain the level similar to Normal group, illustrates that the present invention is stabilized cell membrane fluidity to the mechanism of preservation of myocardial cell.
Three, the present invention (embodiment 1 preparation) pharmaceutical composition is to cultivating myocardial cell LPS attack model endocellular liberation ca
++the impact of concentration, as following table 32
Table 32 pair is cultivated myocardial cell LPS attack model endocellular liberation ca
++the impact of concentration
(nmol/L)
Between group, compare: G3:G4t=4.7253P < 0.01 ※ ※
G3:G5t=6.7779P < 0.001 (extremely)
From visible LPS (100ul/ml) the pathologic group myocardial cell of table 32, have obvious damage, its endocellular liberation calcium concentration obviously raises.This is intracellular calcium overload, is generally considered to be reversibility in cell and is damaged to dead final common path.Under normal circumstances, the outer liquid Ca++ concentration of myocardial cell is 10
-3nmol/L, and endochylema concentration is only 10 during tranquillization
-7mol/L, both differ approximately 10000 times, and measuring as seen intracellular free calcium is to be of great significance.This experimental result shows that the present invention and pathologic group have very significantly difference (P < 0.01) to illustrate that the present invention may and reduce intracellular calcium overload by stabilized cell membrane fluidity, thus the protective effect of performance to myocardial cell.
Four, the present invention (embodiment 1 preparation) the extracellular fluid electrolytical impact of pharmaceutical composition on Anoxia myocardial cell model, in Table 33.
Table 33 is on the electrolytical n=10 that affects of extracellular fluid
Sodium: compare G2:G3t=1.289P < 0.05 ※ between group
G2：G1t＝8.186P＜0.01※※
Potassium: group is asked comparison G2:G3t=0.456P < 0.5
G2：G1t＝8.563P＜0.01※※
Calcium: group is asked comparison G2:G3t=5.849P < 0.01 ※ ※
G2：G1t＝16.860P＜0.01※※
From table 33, show the visible born of the same parents' extracellular sodium ion concentration (P < 0.05) that obviously reduce of the present invention, but not obvious on potassium ion impact, it is consistent on the impact of extracellular calcium with the experiment of cytosolic free calcium concentration in cardiomyocyte concentration, the outer calcium ion of born of the same parents of pathologic group is less than the present invention's (embodiment 1 preparation) pharmaceutical composition group (P < 0.01), illustrate because pathologic group cell injury, intracellular calcium overload, so extracellular calcium is less than Herba mesonae chinensis; Middle dose of group, proving again the present invention can stabilized cell in calcium, reduce the damage of myocardial cell, thereby cell membrane has protective effect.
Five, the present invention (the embodiment 1 preparation) impact of pharmaceutical composition on the myocardium enzyme LDH of myocardial cell, in Table 34
Table 34 is on the impact of myocardium enzyme LDH (u/L)
From table 34 medicine serum group, be starkly lower than pathologic group, illustrate that the present invention has protective effect to myocardial cell.When myocardial cell is after damage, LDH leaks in culture medium in cell, and the LDH of take can reflect the protective effect of this medicine to myocardial cell as index.
Six, the present invention (embodiment 1 preparation) pharmaceutical composition on myocardial cell injury after the impact of Endothelin, in Table 35
The impact of table 35 on Endothelin (ET)
From table 35 prompting medicine serum group Endothelin, significantly lower than pathologic group (P < 0.01), illustrate that the present invention can pass through to reduce ET, thereby reduce the impact on myocardial cell.ET outside myocardial cell is very low under normal circumstances, and after cell injury I) q, I] ET raises.This experimental result is consistent with ET experiment in ventricular muscles tissue, illustrates that the present invention has the effect of protecting myocardial cell.
Experimental example 6: the clinical research physical data of the present invention's (embodiment 1 preparation) medicine composite for curing 48 routine chronic renal failures:
Selection meets chronic renal failure diagnostic criteria, renal function by stages at II more than the phase, and Chinese medical discrimination belongs to spleen kidney qi (sun) deficiency syndrome, and the course of disease surpasses 6 months and gets rid of reversible factors person as observing case.Patient is divided into treatment group and matched group at random, and number of cases is respectively 48 and 30.10 examples of being in hospital in treatment group patient, outpatient service 38 examples; Male's 28 examples, women's 20 examples, age 26-65 year, average 49.90 ± 12.70.8 examples of being in hospital in matched group patient, outpatient service 22 examples, male's 18 examples, women's 12 examples, age 27-64 year, average 47.40 ± 11.63, the course of disease is the shortest 9 months, the longest by 22, average 5.29 ± 5.11 years.Two groups of ordinary circumstances are learned by statistics and are processed relatively, and there was no significant difference, has comparability.
Observational technique:
1, Therapeutic Method treatment group gives pharmaceutical composition of the present invention, by Xiyuan Hospital, Chinese Medicine Academy of China's experiment pharmaceutical factory, is produced, and every bag containing 15 grams of crude drugs, each 2 bags, every bu 2 times.Matched group gives NIAODUQING electuary, and by Guangzhou, pharmaceutical factory of Nanfang Hospital produces, and each 1 bag, every day 4 times.Two groups all adopt diet control and the conventional symptomatic treatment of doctor trained in Western medicine, as corrected acidosis and water, electrolyte disturbance, if there is the infected, give anti-infective therapy; Hyperpietic, gives depressor treatment etc.Within 2 months, be 1 course for the treatment of, all patients all treated for 2 courses for the treatment of.
2, observation index: tcm symptom and sign, renal function (Ccr, Scr, BUN), blood fat (TG, TC), Endothelin (ET), parathyroid hormone (PTH) and ultrasoundcardiogram.
3, statistical method: enumeration data X 2 test, measurement data adopts t check, and ranked data adopt Ridit check
Result:
1, curative effect determinate standard is effective: A, clinical symptom relief or disappearance; B, endogenous creatinine clearance rate increase >=30%; C, serum creatinine reduce >=30%; Effective: A, clinical symptom relief or disappearance; B, endogenous creatinine clearance rate >=20%; C, serum creatinine reduce >=20%; Invalid: clinical manifestation and lab testing are all not improved or deterioration person.
2, clinical curative effect analysis: effective 14 examples for the treatment of group (29.17), effective 23 examples (47.92%), invalid 11 examples (22.92%), total effective rate is 77.08%.Effective 4 examples of matched group (13.33%), effective 17 examples (56.67%), no effect 9 (30%), total effective rate is 70%.Two groups of curative effects are learned by statistics and are processed relatively, there was no significant difference, and obvious effective rate is learned processing by statistics, u=59.14, P < 0.01, has significant differences.
3, the improvement situation comparison of two groups of cardinal symptoms: pharmaceutical composition of the present invention is better than NIAODUQING electuary to the improvement that patient's fatigue and weakness, waist soreness, nocturia increase, cardiopalmus is seized with terror, learns and processes by statistics, and P < 0.05, has significant difference.
4, the variation comparison of renal function before and after two groups of treatments, in Table 36.
The situation of change of renal function before and after table 36 liang group treatment
| Group | Number of cases | Ccr(ml/min) | Scr(umol/l) | BUN(mmol/l) |
| Treatment group | ||||
| Before treatment | 48 | 10.77±9.44 | 555.04±318.80 | 26.10±15.6 |
| After treatment | 48 | 18.46±15.84△△ | 420.74±239.19△ | 21.96±13.84 |
| Matched group | ||||
| Before treatment | 30 | 13.33±9.10 | 430.35±234.63 | 23.91±12.02 |
| After treatment | 30 | 14.12±13.02 | 400.43±168.99 | 27.86±18.24 |
With before treatment relatively: △ P < 0.05 △ △ P < 0.01 time with.
From table 36, renal function after medicine composite for curing of the present invention (Ccr, Scr, BUN) is all improved, and learns and processes by statistics, and before and after treatment, Ccr, Scr have significant difference (P < 0.01).NIAODUQING electuary group renal function improves not obvious.Other two groups of Ccr, Scr, BUN improve there was no significant difference (P < 0.01).
5, the situation of change of hemoglobin and plasma protein before and after two groups of treatments, in Table 37.
The situation of change (X ± S) of hemoglobin and plasma protein before and after table 37 liang group treatment
| Group | Number of cases | Ccr(ml/min) | Scr(umol/l) | BUN(mmol/l) |
| Treatment group | ||||
| Before treatment | 48 | 87.74±25.43 | 41.67±6.53 | 66.68±8.35 |
| After treatment | 48 | 98.02±25.03△ | 42.97±5.78 | 67.59±12.25 |
| Matched group | ||||
| Before treatment | 30 | 87.93±32.49 | 43.04±3.4 | 69.37±5.026 |
| After treatment | 30 | 94.23±26.47 | 42.52±3.5 | 69.72±7.14 |
From table 37, pharmaceutical composition of the present invention can significantly improve the renal anemia that chronic renal failure causes, suitable with the effect of NIAODUQING electuary group.
6, Blood Lipid situation comparison before and after two groups of treatments, in Table 38.
The impact of table 38 pharmaceutical composition of the present invention on blood fat
| Number of cases | Before treatment | After treatment | |
| Cholesterol (mmol/L) | 42 | 5.21±1.81 | 4.08±1.84△△ |
| Triglyceride (mmol/L) | 42 | 2.13±1.19 | 1.64±0.99△ |
From table 38, pharmaceutical composition of the present invention has remarkable effect for reducing blood fat, and prompting the present invention can correct metabolism disorder of blood lipid, not only can delay CRF, can also prevent and treat the generation of cardiovascular complication.
7, the impact of pharmaceutical composition of the present invention on Endothelin (ET) and parathyroid hormone (PTH): in Table 39.
The impact of table 39 pharmaceutical composition of the present invention on Endothelin and parathyroid hormone
| Number of cases | Before treatment | After treatment | |
| ET(pg/ml) | 11 | 80.56±40.23 | 50.67±16.18△ |
| PTH(pg/ml) | 11 | 262.18±105.34 | 156.51±119.21△ |
From table 39, pharmaceutical composition of the present invention can obviously reduce CRF and cause that ET raises and PTH raises, thereby plays the protective effect to heart kidney.
8, the impact of pharmaceutical composition of the present invention on heart damage: in Table 40.
The impact of table 40 pharmaceutical composition of the present invention on heart
| Project | Number of cases | Before treatment | After treatment | P value |
| Left ventricle anteroposterior diameter | 11 | 48.67±2.83 | 48.87±3.18 | ＞0.05 |
| Left ventricle spacer thickness | 11 | 8.67±1.23 | 8.22±0.44 | ＞0.05 |
| LVEF | 11 | 70.22±11.21 | 69.22±11.64 | ＞0.05 |
| Left ventricular posterior wall thickness | 11 | 7.61±0.82 | 8.11±1.27 | ＞0.05 |
| Mevf | 11 | 9.24±2.32 | 8.55±2.29 | ＞0.05 |
| EPSS | 11 | 4.64±2.36 | 6.25±2.63 | ＞0.05 |
| Left atrium diameter l | 11 | 32.11±3.18 | 31.67±1.80 | ＞0.05 |
| Chamber anteroposterior diameter again | 11 | 17.63±4.21 | 17.63±3.82 | ＞0.05 |
| Two class lobe peak velocities | 11 | 0.70±0.22 | 0.63±0.17 | ＞0.05 |
| Bicuspid valve A peak flow velocity | 11 | 0.74±0.21 | 0.77±0.21 | ＞0.05 |
| Bicuspid valve A/E value | 11 | 1.09±0.47 | 1.25±0.32 | ＞0.05 |
| Tricuspid valve peak velocity | 11 | 0.52±0.08 | 0.58±0.16 | ＞0.05 |
| Aorta peak velocity | 11 | 1.04±0.18 | 1.13±0.37 | ＞0.05 |
| Pulmonary artery peak velocity | 11 | 0.88±0.16 | 0.95±0.19 | ＞0.05 |
| Aortic valve opening extent | 11 | 18.78±1.64 | 18.67±1.32 | ＞0.05 |
| Aortic valve internal diameter | 11 | 20.11±1.90 | 20.56±1.42 | ＞0.05 |
| Aortic sinus portion anteroposterior diameter | 11 | 31.00±3.35 | 31.00±2.78 | ＞0.05 |
From table 40; before and after medicine composite for curing group patient's of the present invention echocardiography indices treatment, without significance, change; show not increase the weight of at period in a medicine heart damage, thereby the heart damage that prompting pharmaceutical composition of the present invention causes CRF has certain protective effect.
Embodiment 1
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 2 times, and 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filtered, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 (50 ℃), adds Cordyceps fine powder, mixes to obtain compositions.Get compositions 1g, sucrose 2g, dextrin 1g, granulation, dry, make 1000g, obtain.
Embodiment 2
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 2 times, 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filters, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 (50 ℃), add Cordyceps fine powder, mix to obtain compositions, according to conventional method, add conventional adjuvant to make capsule.
Embodiment 3
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 2 times, and 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filters, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 (50 ℃), add Cordyceps fine powder, mix compositions according to conventional method, add conventional adjuvant to make tablet.
Embodiment 4
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 2 times, and 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filtered, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 (50 ℃), adds Cordyceps fine powder, mixes to obtain compositions, makes oral liquid.
Embodiment 5
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 2 times, 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filters, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 (50 ℃), add Cordyceps fine powder, mix to obtain compositions, according to conventional method, add conventional adjuvant to make concentrated pill.
Embodiment 6
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 2 times, and 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filters, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 (50 ℃), add Cordyceps fine powder, mix compositions according to conventional method, add conventional adjuvant to make pill.
Claims (17)
1. treat a pharmaceutical composition for chronic renal failure, it is characterized in that this pharmaceutical composition crude drug consists of:
2. pharmaceutical composition as claimed in claim 1, is characterized in that this pharmaceutical composition crude drug consists of:
3. pharmaceutical composition as claimed in claim 1, is characterized in that this pharmaceutical composition crude drug consists of:
4. the pharmaceutical composition as described in as arbitrary in claim 1-3, is characterized in that the Herba Epimedii in this pharmaceutical composition crude drug is processed with honey Herba Epimedii.
5. pharmaceutical composition as claimed in claim 1, is characterized in that above nine tastes make the ejection preparation of clinical acceptance.
6. the preparation method of the pharmaceutical composition as described in as arbitrary in claim 1-3, is characterized in that the method is:
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 1-3 time, each 1-2 hour, and collecting decoction, filters, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 at 50 ℃, adds Cordyceps fine powder, mixes; According to common process, add conventional adjuvant to make the capsule of clinical acceptance, granule, tablet, pill, slow releasing agent, oral liquid.
7. the preparation method of the pharmaceutical composition as described in as arbitrary in claim 1-3, is characterized in that the method is:
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 1-3 time, each 1-2 hour, and collecting decoction, filters, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 at 50 ℃, adds Cordyceps fine powder, mixes; According to common process, add conventional adjuvant to make the drop pill of clinical acceptance, concentrated pill or mixture.
8. the preparation method of pharmaceutical composition as claimed in claim 4, is characterized in that the method is:
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other processed with honey Herba Epimedii decoct with water 1-3 time, each 1-2 hour, and collecting decoction, filters, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 at 50 ℃, adds Cordyceps fine powder, mixes; According to common process, add conventional adjuvant to make the capsule of clinical acceptance, granule, tablet, pill, slow releasing agent, oral liquid.
9. the preparation method of pharmaceutical composition as claimed in claim 4, is characterized in that the method is:
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other processed with honey Herba Epimedii decoct with water 1-3 time, each 1-2 hour, and collecting decoction, filters, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 at 50 ℃, adds Cordyceps fine powder, mixes; According to common process, add conventional adjuvant to make the drop pill of clinical acceptance, concentrated pill or mixture.
10. the preparation method of pharmaceutical composition as claimed in claim 6, is characterized in that the capsule in the method is soft capsule.
The preparation method of 11. pharmaceutical compositions as claimed in claim 6, is characterized in that the method is:
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 2 times, and 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filtered, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 at 50 ℃, adds Cordyceps fine powder, mixes; According to common process, add conventional adjuvant to make the capsule of clinical acceptance, granule, tablet, pill, slow releasing agent, oral liquid.
The preparation method of 12. pharmaceutical compositions as claimed in claim 7, is characterized in that the method is:
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other Herba Epimedii decoct with water 2 times, and 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filtered, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 at 50 ℃, adds Cordyceps fine powder, mixes; According to common process, add conventional adjuvant to make the drop pill of clinical acceptance, concentrated pill or mixture.
The preparation method of 13. pharmaceutical compositions as claimed in claim 8, is characterized in that the method is:
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other processed with honey Herba Epimedii decoct with water 2 times, and 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filtered, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 at 50 ℃, adds Cordyceps fine powder, mixes; According to common process, add conventional adjuvant to make the capsule of clinical acceptance, granule, tablet, pill, slow releasing agent, oral liquid.
The preparation method of 14. pharmaceutical compositions as claimed in claim 9, is characterized in that the method is:
Above nine tastes, Cordyceps is ground into fine powder; Eight tastes such as all the other processed with honey Herba Epimedii decoct with water 2 times, and 2 hours for the first time, 1.5 hours for the second time, collecting decoction, filtered, and filtrate is condensed into the clear paste that relative density is 1.28-1.32 at 50 ℃, adds Cordyceps fine powder, mixes; According to common process, add conventional adjuvant to make the drop pill of clinical acceptance, concentrated pill or mixture.
The preparation method of 15. pharmaceutical compositions as claimed in claim 11, is characterized in that the capsule in the method is soft capsule.
The application of 16. pharmaceutical compositions as described in as arbitrary in claim 1-3 in the medicine of preparation treatment chronic renal failure.
The application of 17. pharmaceutical compositions as claimed in claim 4 in the medicine of preparation treatment chronic renal failure.
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| 肾衰冲剂调节慢性肾衰竭大鼠血液动力学改善肾功能的研究;高建东等;《中国中西医结合肾病杂志》;20030430;第4卷(第4期);223-224 * |
| 高建东等.肾衰冲剂调节慢性肾衰竭大鼠血液动力学改善肾功能的研究.《中国中西医结合肾病杂志》.2003,第4卷(第4期),223-224. |
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