CN104435698A

CN104435698A - Traditional Chinese medicine compound preparation for treating severe IgA nephropathy

Info

Publication number: CN104435698A
Application number: CN201310426475.2A
Authority: CN
Inventors: 邓跃毅; 钟逸斐; 蔡小凡; 许超; 其他发明人请求不公开姓名
Original assignee: Longhua Hospital Affiliated to Shanghai University of TCM
Current assignee: Longhua Hospital Affiliated to Shanghai University of TCM
Priority date: 2013-09-18
Filing date: 2013-09-18
Publication date: 2015-03-25

Abstract

The invention discloses a traditional Chinese medicine compound preparation for treatingsevere IgA nephropathy. The preparation is prepared from the following raw materials by weight: 10-30 parts of poria, 10-15 parts of fried atractylodes, 10-20 parts of stir-baked polygonatum rhizome with yellow rice wine, 10-15 parts of fried white peony root, 10-20 parts of Chinese angelica, 10-20 parts of yellow rice wine steamed fructus ligustri lucidi, 6-12 of common macrocarpium fruit prepared with wine, 15-30 parts of Chinese violet and 10-20 parts of rehmannia glutinosa. In addition, the invention also discloses a preparation method and application of the traditional Chinese medicine compound preparation.

Description

Compound Chinese medicinal preparation for the treatment of serious symptom IgA nephropathy and its production and use

Technical field

The present invention relates to a kind of compound Chinese medicinal preparation for the treatment of serious symptom IgA nephropathy, in addition, the invention still further relates to preparation method and the purposes of this Chinese medicine preparation.

Background technology

In China, IgA nephropathy be in current primary glomerulopathy Renal biospy recall rate the highest, account for the maximum disease of renal replacement therapies ratio.The age of onset of this disease based in, young, and most of conditions of patients is progressivity, wherein about has the IgA nephropathy patient of 15-40% will develop into end-stage renal failure gradually after making a definite diagnosis 10-20.So far, IgA nephropathy there is no the remedy measures of specially good effect, and the IgA nephropathy that especially pathological is heavier does not still have good Therapeutic Method become ESRD to delay disease progression and enter renal replacement therapies.

Clinical Western medicine mainly still concentrates on immunization therapy aspect for the treatment of serious symptom IgA nephropathy.Is simple hormone therapy confirmed its effectiveness for the treatment of by multinomial result of study, but correspondence uses in which kind of pathological change? how to use? when stop using? not yet reach unified common recognition.In addition, when treating patient also need to bear may due to hormone therapy bring as untoward reaction such as infection, metabolism disorder, osteoporosises.Therefore, in IgA nephropathy treatment, still there is dispute.For other Immunotherapy regimens, more do not follow card and learn according to confirming, the more alone hormone of immunosuppressant associating hormone can play better Renoprotective Effect.

Summary of the invention

In order to current immunosuppressive drug can be overcome for the shortcoming in the treatment of serious symptom IgA nephropathy, according to embodiment, the present invention wishes to provide a kind of without obvious toxic-side effects, the compound Chinese medicinal preparation of the serious symptom IgA nephropathy state of an illness be can clearly improve and alleviate again, thus the therapeutic effect of serious symptom IgA nephropathy, the quality of life of raising patient strengthened.In addition, the present invention also wishes to propose aforementioned compound Chinese medicinal preparation and medical usage thereof.

There is no the description to IgA nephropathy in TCM Document, through clinical position accumulation for many years and show the research of multinomial IgA nephropathy TCM Syndrome Type, in pathology and the heavier patient of clinical manifestation, the ratio of differential diagnosis in tcm shared by liver-kidney yin deficiency is very high.Inventor thinks: IgA nephropathy belongs to deficiency in origin and excess in superficiality mostly, based on void, the card of simulataneous insufficiency and excessive, serious symptom IgA nephropathy belongs to the state of an illness stage of deficiency in origin and excess in superficiality, simulataneous insufficiency and excessive, and many at the initial stage of a disease due to the moon, to lose spleen weak, in addition caused by wind heat, noxious dampness.Protracted inflammation, recurrent exerbation, cause healthy energy gradually to be hindered, deficiency of kidney yin, the kidney failing to nourish the liver, so that the hepatic and renal YIN deficiency.Chinese medicine Radix Rehmanniae property is put down, and abnormal smells from the patient is pure quiet, and " energy tonifying five ZANG-organs Kidney-Yin ", " vigour in energy the kidney invigorating " are the monarch drug of we, compatibility Fructus Corni, Fructus Ligustri Lucidi two taste enter kidney, liver two warp, nourishing the liver and kidney, tonifying YIN nourish blood, and Poria, the Rhizoma Atractylodis Macrocephalae, Rhizoma Polygonati replenishing QI to invigorate the spleen are wet with Jiao in change, Radix Paeoniae Alba tonifying YIN easing the affected liver.In addition, inventor thinks that with the passing of time IgA nephropathy is often delayed, and the course of disease is very long, so-called " prolonged illness causes the stasis of blood, pathogen usually intruding into collateral in protracted disease ", therefore polygamy closes the product selecting some blood circulation promoting and blood stasis dispelling when treating." book on Chinese herbal medicine just " has cloud: " its gas is light and pungent for Radix Angelicae Sinensis, its sweet in the mouth and weighing, therefore specially can enrich blood, therefore again can promoting the circulation of blood, and invigorating middle warmer has, and have benefit, the gas medicine in sincere blood in row, the panacea also in blood also." assistant can blood circulation promoting and blood stasis dispelling, nutrition blood, QI invigorating spermatogenesis can be supported again, when being first-selected.What also separately add with waste heat after Herba Violae relieving the exterior syndrome sensible heat heresy in side is clear, becomes nourishing the liver and kidney one side altogether.

Thus, according to embodiment, the compound Chinese medicinal preparation for the treatment of serious symptom IgA nephropathy provided by the invention, its innovative point is, it is prepared from by the crude drug of following weight proportioning: Poria 10-30; Rhizoma Atractylodis Macrocephalae (parched) 10-15; Stir-baked RHIZOMA POLYGONATI with yellow rice wine 10-20; Radix Paeoniae Alba (parched) 10-15; Radix Angelicae Sinensis 10-20; Wine Fructus Ligustri Lucidi 10-20; Wine Fructus Corni 6-12; Herba Violae 15-30; Radix Rehmanniae 10-20.

According to embodiment, in the compound Chinese medicinal preparation of aforementioned therapies serious symptom IgA nephropathy of the present invention, its dosage form is granule.

According to embodiment, the preparation method of the compound Chinese medicinal preparation granule of aforementioned therapies serious symptom IgA nephropathy of the present invention, comprises the steps: weighting raw materials by crude drug mix homogeneously by weight ratio, dry granulation, cross 18-40 mesh sieve, pack by the specification of every bag of 10g.

Compound Chinese medicinal preparation of the present invention is shown by evaluation of clinical curative effect: more simple hormone therapy better efficacy after compound Chinese medicinal preparation associating hormone therapy of the present invention, all has therapeutic potential improving in clinical symptoms and index etc.In the improvement for renal function and tcm syndrome curative effect, use more merely hormone therapy to have more advantage, and there is not serious untoward reaction, affirm that compound Chinese medicinal preparation of the present invention has clear and definite effectiveness in treatment serious symptom IgA nephropathy, thus make more reasonably clinical treatment, improve curative effect, to delay or to block going down of renal function, effectively reduce dialysis number.

Detailed description of the invention

Below in conjunction with specific embodiment, set forth the present invention further.These embodiments are interpreted as only being not used in for illustration of the present invention limiting the scope of the invention.After the content of having read the present invention's record, those skilled in the art can make various changes or modifications the present invention, and these equivalence changes and modification fall into the scope of the claims in the present invention equally.

Embodiment 1

Take Poria 10g, Rhizoma Atractylodis Macrocephalae (parched) 10g, stir-baked RHIZOMA POLYGONATI with yellow rice wine 10g, Radix Paeoniae Alba (parched) 10g, Radix Angelicae Sinensis 10g, wine Fructus Ligustri Lucidi 10g, wine Fructus Corni 6g, Herba Violae 15g and Radix Rehmanniae 10g, this 9 taste crude drug mix homogeneously, dry granulation, specification by every bag of 10g after crossing 18-40 mesh sieve is packed, hereinafter referred to as nourishing the liver and kidney granule.

Embodiment 2

Take Poria 30g; Rhizoma Atractylodis Macrocephalae (parched) 15g; Stir-baked RHIZOMA POLYGONATI with yellow rice wine 20g; Radix Paeoniae Alba (parched) 15g; Radix Angelicae Sinensis 20g; Wine Fructus Ligustri Lucidi 20g; Wine Fructus Corni 12g; Herba Violae 30g; Radix Rehmanniae 20g.This 9 taste crude drug mix homogeneously, dry granulation, packs, hereinafter referred to as nourishing the liver and kidney granule by the specification of every bag of 10g after crossing 18-40 mesh sieve.

Embodiment 3

Take Poria 20g; Rhizoma Atractylodis Macrocephalae (parched) 12.5g; Stir-baked RHIZOMA POLYGONATI with yellow rice wine 15g; Radix Paeoniae Alba (parched) 12.5g; Radix Angelicae Sinensis 15g; Wine Fructus Ligustri Lucidi 15g; Wine Fructus Corni 9g; Herba Violae 22.5g; Radix Rehmanniae 15g.This 9 taste crude drug mix homogeneously, dry granulation, packs, hereinafter referred to as nourishing the liver and kidney granule by the specification of every bag of 10g after crossing 18-40 mesh sieve.

Embodiment 4

Take Poria 10g; Rhizoma Atractylodis Macrocephalae (parched) 15g; Stir-baked RHIZOMA POLYGONATI with yellow rice wine 10g; Radix Paeoniae Alba (parched) 15g; Radix Angelicae Sinensis 10g; Wine Fructus Ligustri Lucidi 20g; Wine Fructus Corni 6g; Herba Violae 30g; Radix Rehmanniae 10g.This 9 taste crude drug mix homogeneously, dry granulation, packs, hereinafter referred to as nourishing the liver and kidney granule by the specification of every bag of 10g after crossing 18-40 mesh sieve.

Embodiment 5

Take Poria 30g; Rhizoma Atractylodis Macrocephalae (parched) 10g; Stir-baked RHIZOMA POLYGONATI with yellow rice wine 20g; Radix Paeoniae Alba (parched) 10g; Radix Angelicae Sinensis 20g; Wine Fructus Ligustri Lucidi 10g; Wine Fructus Corni 12g; Herba Violae 15g; Radix Rehmanniae 20g.This 9 taste crude drug mix homogeneously, dry granulation, packs, hereinafter referred to as nourishing the liver and kidney granule by the specification of every bag of 10g after crossing 18-40 mesh sieve.

Test example

In order to observe clinical efficacy, clinical efficacy is provided to be reported as follows by attached Longhua hospital of Traditional Chinese Medicine in Shanghai university Urology Department:

1. clinical data

1.1 kind of designs and principle

1.1.1 research design type

The multicenter study of at random, double blinding, contrast.

1.1.2 sample size

Research case derives from Longhua Hospital affiliated Shanghai University Of Chinese Traditional Medicine, Yueyang hospital; The outpatient service of the attached Ren Ji hospital of university of communications's medical college, Sixth Man people hospital and ward.Each center is 20 examples.

1.1.3 random method

Adopt SPSS statistical analysis software produce respectively 80 routine experimenters accept the random number of different therapeutic modality, listing serial number is 001-080, enters therapy of combining Chinese and Western medicine group or western medicine matched group according to after different differential diagnosis in tcm at random in the ratio of 1: 1.

1.1.4 blind is implemented

Adopt double-blind method

1.1.5 contrast method

On glucocorticoid treatment basis, the ratio with 1: 1 is carried out treatment by Chinese herbs medicine and is simulated medicine with Chinese medicine and contrast.This is comparing between therapy of combining Chinese and Western medicine with simple western medical treatment.

1.2 study population

The crowd of this test example belongs to the constitutional serious symptom IgA nephropathy patient of syndrome of yin deficiency of liver and kidney for Chinese medical discrimination.

1.2.1 diagnostic criteria

(1) Western medicine diagnose standard: (according to Wang Haiyan " nephrology " second edition)

A. clinical manifestation: the clinical manifestation with chronic glomerulonephritiss such as hematuria, albuminuria and renal hypofunctions.

B. pathological diagnosis: turn out to be IgA nephropathy through renal fibroblast immunopathogenesis.

C. Secondary cases IgA nephropathy is got rid of.

(2) Standards of Chinese Medical Syndrome Differentiation:

This disease belongs to the traditional Chinese medical science " the kidney-wind syndrome " category.According to the analysis of country's 15 brainstorm subjects, there is dryness with foreign body sensation in the eyes or blurred vision, dizziness or tinnitus, dysphoria with feverish sensation in the chest palms and soles, dry mouth and throat, nocturnal emission or menoxenia in patient, red tongue yellow and thin fur, thready and rapid pulse person can distinguish as syndrome of yin deficiency of liver and kidney.

Table 1: syndrome of yin deficiency of liver and kidney (Chinese medicine syndrome integral)

1.2.2 inclusive criteria

(1) be diagnosed as Primary IgA nephropathy through Renal biospy and clinical examination, and pathological manifestations is LeeShi more than III grade;

(2) in age 18-60 year, sex, nationality are not limit;

(3) CKD<5 phase: eGFR (MDRD) formula >15ml/min/1.73m ²

1.2.3 exclusion standard

(1) once accepted immunosuppressant in nearly 3 months, cytotoxic drug therapy was greater than 4 weeks;

(2) once accept glucocorticoid (prednisone or meticortelone) dosage in nearly 3 months and reach more than 4 weeks more than 20mg/d;

(3) suffers from acute or radical property nephritis person;

(4) suffers from active stage hepatitis B and lasting Liver function grade transaminase disorder person;

(5) suffer from malignant tumor patient or have malignant tumor medical history, HIV history, psychiatric history, acute central nervous system disease, Severe gastrointestinal tract disease, the person that prohibits the use glucocorticoid;

(6) abnormal carbohydrate metabolism, fasting glucose is more than 6.2mmol/L person;

(7) gestation or women breast-feeding their children;

(8) accepting other clinical trial investigators;

(9) merge life-threatening complication as severe infections or there is other organ serious disease and dysfunction person.

The process 1.3 case comes off

Its case notes table will be retained to the case that comes off, write falling-away cause clearly, and using last assay as final result.

The termination of 1.4 research cases

Exit test standard:

1. there is the severe digestive road symptom person of being impatient in treatments period, medicine decrement or postpone using, and symptom resumes treatment after improving, as still can not resistance to receptor;

2. treatments period occurs that glutamate pyruvate transaminase raises, and medicine decrement or postponement use, and check after liver protecting therapy, if glutamate pyruvate transaminase no longer raises, continue test follow up a case by regular visits to, as continue raise, if or 2 weeks after check glutamate pyruvate transaminase still exceed Upper Limit of Normal Value more than 2 times persons;

3. the treatments period person that occurs severe infections;

4. there is gestation, death or person lost to follow-up;

5. patient compliance extreme difference or drug withdrawal were more than 3 weeks persons.

No matter which kind of reason above, its case notes table will be retained to the case exiting test, write the reason stopping test clearly, and using last assay as final result.

2 Therapeutic Method

2.1 Primary Care

(1) dietetic nutrition:

As there is renal hypofunction, by China's " chronic kidney disease proteinaceous nutrient treatment Consensus of experts " suggestion, according to body weight and renal hypofunction degree, giving not commensurability high-quality protein diet, while low protein diet, the absorption of heat should be maintained.

(2) control blood pressure:

To the patient that blood pressure raises, with reference to international JNC V II and K/DOQI diagnosis and treatment standard, should by controlling of blood pressure at below 130/80mmHg.

First antihypertensive drugs applies ACEI or ARB class; Still by controlling of blood pressure to target person, then can be able to not add with CCB and other antihypertensive drugs at such medicine of application.

(3) immunosuppressant therapy adopts prednisone oral medication:

Prednisone initial dose selects 40mg-60mg/d oral according to the situation such as weight in patients, renal hypofunction; Take eight to ten two weeks altogether; After this within every two weeks, subtract 5mg, reduce to 30mg; Monthly subtract 5mg again, about treatment is withdrawn for about 9 months.

2.2 test medications

Investigational agent is Chinese medicine granules, and simulation medicine is low dosage Chinese medicinal granule placebo: by GMP standard production (Tianjiang Pharmaceutical Industry Co., Ltd., Jiangyin).

Nourishing the liver and kidney granule: the nourishing the liver and kidney granule that random selecting embodiment 1-5 is obtained, specification 10g/ wraps.

Using method:

Take each 1 bag of nourishing the liver and kidney granule, every day 2 times is oral;

2.3 observe the course for the treatment of

Totally 48 weeks.

2.4 medication management

Each center director specifies drug control person be responsible for the getting of clinical research medicine, keeping and drop by the wayside and the recovery of case research medication lost to follow-up, return or destruction.

The regulation of 2.5 drug combinations

(1) treatments period, can not apply other immunosuppressant or cell toxicity medicament simultaneously;

(2) treatments period, when hormones is treated, can add and avoid osteoporosis with calcium preparation, calcitriol etc., also can add and use all kinds of gastric mucosa protectant;

(3) treatments period, as occurred, anemia can add with chalybeate and erythropoietin;

(4) treatments period, as dyslipidemia occurs person, with reference to China's blood fat remedial proposal in 1997 and U.S.'s calendar year 2001 " NCEP third time report (NCEPATP III) " standard, make T-CHOL <5.72mmol/L (<220mg/dl), LDL-C <3.64mmol/L (<140mg/dl), triglyceride <2.26mmol/L (<200mg/dl).Lipid-regulation medicine can select his class D or the special class of shellfish oral;

(5), as there is the complication such as severe electrolyte, infection, heart failure or anti symptom treatment should being given in time when there is untoward reaction in treatments period.

2.6 observation index

General data: body weight, blood pressure etc.

Curative effect index:

(1) leading indicator

Glomerular filtration rate (MDRD formulae discovery), serum creatinine

(2) secondary index

A.24 hours urine protein quantitatively, urine erythrocyte

B. symptom improves situation: tcm syndrome changes

Above index all needs to detect for following up a case by regular visits at every turn.

(3) endpoints

Glomerular filtration rate declines and reaches 50%, and serum creatinine is double

Safety indexes:

A. routine blood test, liver function, blood fat

B. stool routine, excrement occult blood, electrocardiogram

Above a is that treatments period detects once for every 24 weeks; B surveys once for each before and after treatment.

The observation cycle:

The time point that observation index gathers: 4 weeks ± 3 days, 12 weeks ± 3 days, 24 weeks ± 3 days, 36 weeks ± 3 days, 48 weeks ± 3 days (as time meet national official holiday, can postpone 5 days).

2.7 adverse events are observed and are analyzed

When finding untoward reaction, researcher can take necessary treatment measures according to conditions of patients, as: adjustment therapeutic dose, suspends treatment etc., and determines whether termination test.When there is serious adverse events, the unit bearing experimental study must take necessary treatment measures immediately, the safety of protection experimenter.All adverse events all answer tracing study to normal or normal, the various ways such as follow-up study mode can be selected in hospital according to the weight of adverse events, outpatient service, phone.Also need itemized record and reporting clinical research responsible department and Ethics Committee.

2.8 Evaluation of Synthetic Effect of Holistic standards

(1) tcm syndrome criterion of therapeutical effect is with reference to (new Chinese medicine guideline of clinical investigations):

A. effective: tcm clinical practice symptom, sign are obviously improved, syndrome integral reduces >=75%;

B. effective: tcm clinical practice symptom, sign take a favorable turn, syndrome integral reduces >=30%;

C. invalid: tcm clinical practice symptom, sign are all not improved, even increase the weight of, syndrome integral subtracts less than 30%.

Note: computing formula is: [before (before treatment the rear integration of integration-treatment)/treatment integration] × 100%

(2) doctor trained in Western medicine criterion of therapeutical effect: (new Chinese medicine guideline of clinical investigations):

A. cure: clinical symptom disappears, and urine erythrocyte is turned out cloudy or 1-2/HP, urine protein is turned out cloudy or lower than 0.2g/24h, normal renal function.

B. effective: clinical symptom substantially disappears or obviously improves, urine erythrocyte counting is comparatively front reduces more than 50%, and urine protein reduces more than 50%, normal renal function.

C. effective: clinical symptom has certain improvement, urine erythrocyte counts minimizing comparatively but lower than 50%, urine protein reduces but lower than 50%, renal function is without deterioration.

D. invalid: clinical symptom is without improvement, and urine erythrocyte counting and urine protein are without minimizing, and renal function is without improvement or worsen.

2.9 statistical analysis

(1) statistical software

Statistical software adopts SPSS18.0

(2) the selection of analytical data collection

FAS crowd.FAS concentrate curative effect relevant portion come off, exit the missing data of case adopt before the last observed data method of (LOCF) of carrying down supplement, the curative effect relevant portion data acquisition linear interpolation method lacked between follow-up period is supplemented.FAS collection is selected to add up after rejecting some cases according to inclusion criteria.

(3) statistical analysis content

Case performance, Baseline Data and efficacy analysis, safety analysis

(4) statistical analysis technique

All statistical test all adopt two-sided test, and P value is less than 0.05 and is considered to checked difference and has statistical significance.

The description of quantitative target calculates mean, standard deviation, median, maximum, minima.

Description all kinds of number of cases and the percent of classification indicators.

A. general information and baseline characteristic

The demographic of patient, the course of disease, baseline clinical index are carried out statistics and described.Baseline is defined as treatment the 0th week (when entering to organize).

According to the numerical characteristic of variable, select independent samples t test or Wilcoxon rank test to carry out baseline to the quantitative data such as age, the course of disease, baseline clinical index of two groups and compare; According to the numerical characteristic of variable, use X 2 test to carry out baseline to sex and compare.

B. influence factor's statistics

For avoiding blood pressure for the impact of therapeutic evaluation, before the treatment, two groups adopt covariance analysis statistics blood pressure situation.

C. curative effect statistics

Clinical effective rate describes with number of cases and percent and uses Ridit(rank test) carry out statistical analysis.

Each clinical efficacy indexes (renal function index, albuminuria, urine erythrocyte and TCM syndrome evaluation), as quantitative data, adopts the method for spss repeated measure to carry out statistical analysis, and is adjusted as covariant by baseline value.When getting rid of Baseline Data interference, compare indices respectively in the test group and matched group of overall grouping and each Syndrome Classification subgroup with the curative effect difference in the group for the treatment of time change and between group, and carry out statistics description.

D. adverse events statistics

Grouping is described and list, calculates the incidence rate often organizing adverse events.List is summed up and is compared generation and the relation of medicine, the order of severity of adverse events of two groups of adverse events.

3. result

3.1 ordinary circumstance

This test example is included first case in from 2011.1 and is started to enter group end to 2012.2, and include 80 cases in altogether, each 40 examples of test group, matched group, complete case load totally 68 examples, a variety of causes exits 12 examples, expulsion rate 15%.

3.2 baseline case

Totally divide into groups during baseline and test group and matched group equal no difference of science of statistics (P>0.05) in the demography such as age, sex index and every clinical laboratory measures in two different pattern of syndrome subgroups, there is comparability.(table 2-4)

Table 2: sex baseline compares

	Treatment group	Matched group	χ ²Value	P value
					Man's (example)	25（65.8%）	23（62.2%）	0.107	0.744
Female's (example)	13（34.2%）	14（37.8%）

Table 3: age and course of disease baseline compare

Table 4: the baseline of Chinese medicine syndrome integral and clinical indices compares

3.3 analysis of Influential Factors

Between blood pressure level two groups of groups for the treatment of front and back treatment group and matched group no significant difference (P>0.05) (see table 5)

Table 5: the comparison of blood pressure

3.4 comparitive study

3.4.1 comprehensive therapeutic effect

(1) tcm syndrome curative effect: tcm syndrome effective percentage is all higher than matched group (P<0.05).(see table 6)

(2) doctor trained in Western medicine curative effect: treated effect two groups of group difference not statistically significants (P>0.05).(see table 7)

Table 6: the efficient comparison of Chinese medicine syndrome integral

Table 7: the efficient comparison of western medical treatment

Because doctor trained in Western medicine curative effect is a kind of the standard of curative effect evaluation that the various index of complex clinical is carried out, the sensitivity of evaluation is not strong, so carry out statistical analysis to specific targets once.

3.4.2 index curative effect

(1) curative effect index:

A.eGFR (MDRD formula)

The results of analysis of variance (degree of freedom of group internal effect adopts Greenhouse-Geisser method to correct) of Repeated Measurement Data shows, the main effect for the treatment of time should have significant difference (P=0.000), there is reciprocal action (P=0.001) treatment time with treatment grouping, the main effect for the treatment of grouping should have significant difference, and test group eGFR change more obviously (P=0.003).(see table 8)

Table 8:eGFR (ml/min/1.73m ²) efficacy analysis of (MDRD formula)

The average speed that b.eGFR declines

Pace of change average speed=(treat the 48th week front eGFR of eGFR-treatment) of the eGFR change weekly { i.e./48 weeks } of eGFR before and after comparative test group and treatment of control group, significant difference (P<0.05) is had between two groups of groups, test group eGFR change value apparently higher than matched group, and be on the occasion of.(see table 9)

The efficacy analysis of table 9:eGFR (MDRD formula) pace of change

C. serum creatinine

The results of analysis of variance (degree of freedom of group internal effect adopts Greenhouse-Geisser method to correct) of Repeated Measurement Data shows, the main effect for the treatment of time should have significant difference (P=0.040), there is reciprocal action (P=0.006) treatment time with treatment grouping, the main effect for the treatment of grouping should have significant difference, and the change of test group serum creatinine more obviously (P=0.010).(see table 10)

Table 10: the efficacy analysis of serum creatinine (umol/l)

(2) secondary efficacy index:

A. Chinese medicine syndrome integral

The results of analysis of variance (degree of freedom of group internal effect adopts Greenhouse-Geisser method to correct) of Repeated Measurement Data shows, the main effect for the treatment of time should have significant difference (P=0.000), treatment time to divide into groups non-interaction action (P=0.387) with treatment, the main effect for the treatment of grouping should have significant difference, and the change of test group TCM syndrome integration more obviously (P=0.016).(see table 11)

Table 11: the efficacy analysis of traditional Chinese medical science integration syndrome (dividing)

B. urine erythrocyte

The results of analysis of variance (degree of freedom of group internal effect adopts Greenhouse-Geisser method to correct) of Repeated Measurement Data shows, the main effect for the treatment of time should have significant difference (P=0.002), treatment time divide into groups non-interaction action (P=0.187) with treatment, the main effect no difference of science of statistics (P=0.332) that treatment is divided into groups.(see table 12)

Table 12: the efficacy analysis of urine erythrocyte (individual/ul)

C.24h urine protein

The results of analysis of variance (degree of freedom of group internal effect adopts Greenhouse-Geisser method to correct) of Repeated Measurement Data shows, the main effect for the treatment of time should have significant difference (P=0.000), treatment time divide into groups non-interaction action (P=0.782) with treatment, the main effect no difference of science of statistics (P=0.405) that treatment is divided into groups.(see table 13)

The efficacy analysis of table 13:24h urine protein (g/d)

3.5 adverse events

There is adverse events 7 example altogether, test group 4 example (10%), matched group 3 example (7.5%).(see table 14-15)

Table 14: test group adverse events is added up

Adverse events	Number of cases	With medicine dependency
			Upper respiratory tract infection	1	May be relevant
Urine sense	2	May be relevant
			Liver damages	1	May be relevant

Table 15: matched group adverse events is added up

Adverse events	Number of cases	With medicine dependency
			Upper respiratory tract infection	1	May be relevant
Urine sense	1	May be relevant
			Liver damages	1	May be relevant

4. conclusion

1) compared with the western medical treatment scheme of simple oral hormone, Chinese and Western is LEE III grade and above Primary IgA nephropathy patient in conjunction with integration scenario (Chinese medicine granules cooperation oral hormone) for pathological manifestations, at Chinese traditional treatment effective percentage, namely alleviate clinical symptoms, aspect of improving the quality of living curative effect is better;

2) compared with the western medical treatment scheme of simple oral hormone, Chinese and Western is have more treatment advantage in LEE III grade and above Primary IgA nephropathy renal function of patients in conjunction with integration scenario (Chinese medicine granules cooperation oral hormone) improving pathological manifestations;

3) Chinese and Western is low in conjunction with integration scenario endpoints incidence rate, and adverse events incidence rate is low, has very high safety.

Claims

1. treat a compound Chinese medicinal preparation for serious symptom IgA nephropathy, it is characterized in that, it is prepared from by the crude drug of following weight proportioning: Poria 10-30; Rhizoma Atractylodis Macrocephalae (parched) 10-15; Stir-baked RHIZOMA POLYGONATI with yellow rice wine 10-20; Radix Paeoniae Alba (parched) 10-15; Radix Angelicae Sinensis 10-20; Wine Fructus Ligustri Lucidi 10-20; Wine Fructus Corni 6-12; Herba Violae 15-30; Radix Rehmanniae 10-20.

2. the compound Chinese medicinal preparation for the treatment of serious symptom IgA nephropathy as claimed in claim 1, it is characterized in that, the weight proportion of crude drug is: Poria 10, Rhizoma Atractylodis Macrocephalae (parched) 10, stir-baked RHIZOMA POLYGONATI with yellow rice wine 10, Radix Paeoniae Alba (parched) 10, Radix Angelicae Sinensis 10, wine Fructus Ligustri Lucidi 10, wine Fructus Corni 6, Herba Violae 15 and Radix Rehmanniae 10.

3. the compound Chinese medicinal preparation for the treatment of serious symptom IgA nephropathy as claimed in claim 1, it is characterized in that, the weight proportion of crude drug is: Poria 30; Rhizoma Atractylodis Macrocephalae (parched) 15; Stir-baked RHIZOMA POLYGONATI with yellow rice wine 20; Radix Paeoniae Alba (parched) 15; Radix Angelicae Sinensis 20; Wine Fructus Ligustri Lucidi 20; Wine Fructus Corni 12; Herba Violae 30; Radix Rehmanniae 20.

4. the compound Chinese medicinal preparation for the treatment of serious symptom IgA nephropathy as claimed in claim 1, it is characterized in that, the weight proportion of crude drug is: Poria 20; Rhizoma Atractylodis Macrocephalae (parched) 12.5; Stir-baked RHIZOMA POLYGONATI with yellow rice wine 15; Radix Paeoniae Alba (parched) 12.5; Radix Angelicae Sinensis 15; Wine Fructus Ligustri Lucidi 15; Wine Fructus Corni 9; Herba Violae 22.5; Radix Rehmanniae 15.

5. the compound Chinese medicinal preparation for the treatment of serious symptom IgA nephropathy as claimed in claim 1, it is characterized in that, the weight proportion of crude drug is: Poria 10; Rhizoma Atractylodis Macrocephalae (parched) 15; Stir-baked RHIZOMA POLYGONATI with yellow rice wine 10; Radix Paeoniae Alba (parched) 15; Radix Angelicae Sinensis 10; Wine Fructus Ligustri Lucidi 20; Wine Fructus Corni 6; Herba Violae 30; Radix Rehmanniae 10.

6. the compound Chinese medicinal preparation for the treatment of serious symptom IgA nephropathy as claimed in claim 1, it is characterized in that, the weight proportion of crude drug is: Poria 30; Rhizoma Atractylodis Macrocephalae (parched) 10; Stir-baked RHIZOMA POLYGONATI with yellow rice wine 20; Radix Paeoniae Alba (parched) 10; Radix Angelicae Sinensis 20; Wine Fructus Ligustri Lucidi 10; Wine Fructus Corni 12; Herba Violae 15; Radix Rehmanniae 20.

7., as the compound Chinese medicinal preparation of the treatment serious symptom IgA nephropathy of claim 1-6 as described in any one, it is characterized in that, its dosage form is granule.

8. treat the preparation method of the compound Chinese medicinal preparation of serious symptom IgA nephropathy as claimed in claim 7, it is characterized in that, by weight ratio weighting raw materials by crude drug mix homogeneously, dry granulation, crosses 18-40 mesh sieve, pack by the specification of every bag of 10g.

9. the application of the compound Chinese medicinal preparation in claim 1-6 described in any one in the medicine of preparation treatment serious symptom IgA nephropathy.