CN107596109A

CN107596109A - A kind of Chinese medicine preparation for treating idiopathic pulmonary fibrosis paracmasis disease and preparation method thereof

Info

Publication number: CN107596109A
Application number: CN201710961846.5A
Authority: CN
Inventors: 吕晓东; 庞立健; 刘创
Original assignee: Liaoning University of Traditional Chinese Medicine
Current assignee: Liaoning University of Traditional Chinese Medicine
Priority date: 2017-10-16
Filing date: 2017-10-16
Publication date: 2018-01-19

Abstract

The invention belongs to field of traditional Chinese, more particularly to a kind of Chinese medicine preparation for treating idiopathic pulmonary fibrosis paracmasis disease and preparation method thereof.The Chinese medicine preparation is made up of the raw material of following weight：130 140 parts of astragalus root, 60 70 parts of wide dragon, 82 88 parts of radix glehniae, 60 70 parts of Radix Angelicae Sinensis, 60 70 parts of Ligusticum wallichii, 60 70 parts of prepared rhizome of rehmannia, 60 70 parts of honey-fried licorice root, 60 70 parts of reticulate millettia, 60 70 parts of the tuber of dwarf lilyturf, 60 70 parts of fritillaria thunbergii.Said preparation is using veins disease theories as guidance, idiopathic pulmonary fibrosis paracmasis interpretation of the cause, onset and process of an illness understanding based on " deficiency syndrome of the lung network stasis of blood ", prescription is prepared with supplementing qi and nourishing yin, promoting blood circulation and removing blood stasis, eliminating the phlegm dredging collateral, it is finally reached and delays idiopathic pulmonary fibrosis progression of disease, alleviate disease symptomses, improve the therapeutic purposes of patients ' life quality.

Description

A kind of Chinese medicine preparation for treating idiopathic pulmonary fibrosis paracmasis disease and its preparation Method

Technical field

The invention belongs to field of traditional Chinese, more particularly to a kind of Chinese medicine for treating idiopathic pulmonary fibrosis paracmasis disease Preparation and preparation method thereof.

Background technology

Idiopathic pulmonary fibrosis (idiopathic pulmonary fibrosis, IPF) is a kind of agnogenic slow Property inflammatory interstitial lung disease, the disease with the alveolar spaces inflammatory reaction of idiopathic and alveolar structure it is disorderly for main pathology it is special Sign.Due to lung effectively take a breath area reduce, most idiopathic pulmonary fibrosis ultimately succumb to injury of lungs and it is conditions associated with hypoxia breathing decline Exhaust.In recent years, because HRCT etc. checks the popularization of equipment, on the incidence of disease of idiopathic pulmonary fibrosis and positive diagnosing rate are gradual Rise.Patient once makes a definite diagnosis idiopathic pulmonary fibrosis, its life span only 3-5.Epidemiological study shows, the IPF incidence of disease About 16.3/10 ten thousand, and acute exacerbation incidence is 20.7% in 3 years.Pathogenesis on IPF fails to understand a variety of be present Say, at present, several theories main are as follows：Cytokine network is unbalance, epithelium mesenchymal cell conversion, matrix generation with Degrade unbalance, oxidative and anti-oxidative is unbalance, Apoptosis, Th1 cells（I type helper cell）The factor and Th2 cells（II type is auxiliary Help T cell）The factor reacts unbalance theory etc..Because its pathogenesis is failed to understand, clinical effectively treatment means are few at present for the disease, except lung Beyond transplanting, Nintedanib and pirfenidone are the medications that guide is recommended in 2015, but because of expensive, domestic not yet list and Clinical practice is less, and other drugs or treatment method lack strong evidence-based medical and supported.

At present, hormone is the common drug for mitigating symptom in the domestic treatment idiopathic pulmonary fibrosis later stage, but prolonged application, tool There are a side effects such as hormone dependant, osteoporosis, the compliance of patient is poor.Chinese medicine idiopathic pulmonary fibrosis, which has to mitigate, suffers from The symptom of person, improve the quality of living, the advantage of Small side effects, being shared with hormone has the function that Synergistic attenuation.

Therefore, developing a kind of Chinese medicine preparation for treating idiopathic pulmonary fibrosis paracmasis disease turns into urgently to be resolved hurrily at present Problem.

The content of the invention

Present invention aims at a kind of Chinese medicine preparation for treating the idiopathic pulmonary fibrosis paracmasis is provided, said preparation is with network disease Theory the idiopathic pulmonary fibrosis paracmasis interpretation of the cause, onset and process of an illness understanding based on " deficiency syndrome of the lung network stasis of blood ", prepares prescription with supplementing qi and nourishing yin, work to instruct Blood stagnation resolvation, eliminating the phlegm dredging collateral, it is finally reached and delays idiopathic pulmonary fibrosis progression of disease, alleviate disease symptomses, improves minimal invasive treatment The therapeutic purposes of quality.

To realize the therapeutic purposes of the present invention, what the present invention was realized in：One kind treats idiopathic pulmonary fibrosis alleviation The Chinese medicine preparation of phase disease, the Chinese medicine preparation are made up of the raw material of following weight：Astragalus root 130-140 parts, wide dragon 60-70 parts, radix glehniae 82-88 parts, Radix Angelicae Sinensis 60-70 parts, Ligusticum wallichii 60-70 parts, prepared rhizome of rehmannia 60-70 parts, honey-fried licorice root 60-70 parts, Reticulate millettia 60-70 parts, tuber of dwarf lilyturf 60-70 part, fritillaria thunbergii 60-70 parts.

Preferably, the Chinese medicine preparation is made up of the raw material of following weight：Astragalus root 132g, wide dragon 66g, north are husky Join 88g, Radix Angelicae Sinensis 66g, Ligusticum wallichii 66g prepared rhizome of rehmannia 66g, honey-fried licorice root 66g, reticulate millettia 66g, tuber of dwarf lilyturf 66g, fritillaria thunbergii 66g.

Monarch drug in a prescription is astragalus root and the composition of wide dragon in the Chinese medicine preparation.

The formulation of the Chinese medicine preparation is mixture or granule.

The Chinese medicine preparation is combined with hormone and treats answering in idiopathic pulmonary fibrosis paracmasis disease medicament as preparation With.

A kind of preparation method for the Chinese medicine preparation for treating idiopathic pulmonary fibrosis paracmasis disease, the preparation method include with Lower step：

Weigh the Ten Herbs in claim 1, fritillaria thunbergii is given as one thinks fit cataclasm, is mixed with remaining nine taste medicine, is first given and drinking before decocting medicinal herbs Cold water soak 30-45 minutes, water did not had 1 middle finger, 2-4 centimetres, and rear plus 8 times of amount decoctings boil 3 times, 1 hour every time, collecting decoction, Filtration, is concentrated into 1000ml, and dispensed.

Taken 2 days by formula, it is twice daily, early to take within 30 minutes before meals（50-75ml）, supper half an hour after takes（50- 75ml）, the Chinese medicine preparation is heated before taking；More than half an hour is separated with other Chinese patent drugs, Western medicine；During medication, forbid taking With pungent, fish raw meat, stimulating food, raw food, greasy, sour and astringent F＆B.

A kind of quality determining method for the Chinese medicine preparation for treating idiopathic pulmonary fibrosis, through high effective liquid chromatography for measuring, It is its index composition to determine the Astragaloside IV in astragalus root, calycosin glucoside, yellow using Astragaloside IV, Mao Ruiyi Ketone glucoside is as this product assay composition, and for controlling this quality, astragalus root must not be less than in terms of Astragaloside IV 10mg, in terms of calycosin glucoside, 4mg must not be less than.

Medicine composition of the present invention and side's solution are as follows：

Chinese medicine preparation provided by the invention is using veins disease theories as academic thought, based on to the idiopathic pulmonary fibrosis paracmasis " deficiency syndrome of the lung The pathogenesis understanding of the network stasis of blood ", with " qi-restoratives dredging collateral " to treat big method, with Qing Dynasty's Wang Qingren it《The correction of the errors of medical works》Yang-tonifying also five Soup composition carries out plus-minus for basic prescription and formed.

Astragalus root, wide dragon are monarch drug in a prescription in side.Astragalus root, it is sweet, it is warm-natured.Return lung, the spleen channel, function tonifying Qi and lifting yang, honey are processed The effect of its tonifying middle-Jiao and Qi can be strengthened.In addition, the Radix Astragali, which also has, nourishes kidney qi, the work(of replenishing and activating blood.《The Decoction and Material Medica》Say:The Radix Astragali " soft taste, be and the dirty vigour of kidney tonifying for Central Region medicine ... ..., be inner medicine ".《Japan hanako materia medica》Record:The Radix Astragali " helps gas, strengthened Muscles and bones, put on flesh, enrich blood ", there is the Zhang Yuansu speech Radix Astragali to treat " blood vessels are not all right " again.Earthworm nature and flavor are salty-cold,《Compendium of Materia Medica》Referred to as For with clearing and activating the channels and collaterals, promoting blood circulation and removing blood stasis, while can relieving asthma.The two benefit one is logical, plays qi-restoratives dredging collateral and is used.Ministerial drug is husky for north Ginseng, Radix Angelicae Sinensis, Ligusticum wallichii are ministerial drug altogether.Radix glehniae cold nature, sweet, slight bitter, return lung the spleen channel, there are nourishiing yin to clear away the lung-heat, the work of expelling phlegm and arresting coughing With.It is generally believed that for radix glehniae is compared with adenophora tetraphylla, it is longer than foster lung yin,《The new compilation of materia medica》Record:" radix glehniae, sweetness and bitterness are slightly cold, taste Light body is light.Special tonifying lung is cloudy, clearing lung-heat fire ",《Herbal justice》Say：" heat of clearing lung-heat stomach, supporting the moon of lung stomach ".Astragalus root, radix glehniae two The same return lung of person, spleen, kidney three are dirty, play the work(of tonifying Qi enriching yin, nourshing blood and promoting blood circulation altogether with the Radix Astragali.Radix Angelicae Sinensis is sweet, pungent, warm, Return liver, the heart, the spleen channel. 《Book on Chinese herbal medicine is just》Record：" Radix Angelicae Sinensis, its is sweet and weighs, therefore can specially enrich blood, and its gas is light and pungent, therefore and can promoting circulation of blood, and bowl spares has, in row There is a benefit, the gas medicine in sincere blood, the also panacea in blood.About assistant is then mended with mending, therefore can be supported nutrition blood, tonifying Qi production of sperm, is pacified five Dirty, strengthen body, beneficial mind, all tangible deficient diseases are omni-benefiting.”《Book on Chinese herbal medicine is newly organized》：" Radix Angelicae Sinensis, acrid-sweet flavor, temperature, can rise can Drop, the YIN aspect of YANG are nontoxic.Though there is point up and down, and enrich blood then one.It is dirty to enter the heart, spleen, liver three.But its property is very dynamic, the Qi-tonifying drug entered In then tonifying Qi, then enrich blood in the antianaemics entered, without determining work(." Ligusticum wallichii property and flavor of peppery and warm perfume (or spice) is dry.Its property is walked without keeping, Ji Nenghang Dissipate, enter blood system again, promoting blood circulation active force is strong.Its property of Radix Angelicae Sinensis, Ligusticum wallichii is dynamic to alter, and bowl spares has row, must be mended in row, to control the guiding principle of blood Neck, also main gas is used, and its matter is slightly moistened, non-dry the ratio between strong.Adjutant is reticulate millettia, cultivated land, bulb of thunberg fritillary.Reticulate millettia is bitter in taste, It is sweet, temperature.Main enter liver, kidney two warp, there is the effect of replenishing and activating blood, menstruation regulating dredging collateral, with returning, rhizome of chuanxiong control the loss of qi and blood altogether.Prepared rhizome of rehmannia Sweet, slight bitter, tepor, the thoughts of returning home, liver and kidney channel, function tonifying blood and regulating menstruation, enriching yin and nourishing kidney.Cultivated land enter liver kidney and the special nourishing the blood and yin of work(, are filled out Lean marrow, kidney-KIN being deficient person, it can all use it.《Compendium of Materia Medica》Record, " the ripe then tepor of glutinous rehmannia ..., and kidney tonifying, the blood person of declining need to use It ",《Medicine origin》Say, " prepared rhizome of rehmannia ... is enriched blood, and void is insufficient, and the people that deficient blood declines must use ".Tuber of dwarf lilyturf cold nature, sweet and slightly bitter taste, The thoughts of returning home, lung, stomach, work(can yin-nourishing Tianjin, dry moistening lungs.《Medicine reflects》Say, the tuber of dwarf lilyturf is " micro- cloudy in sun.The moon is lung medicine, and micro- the moon removes it in lung Fu Huo, fire go then lung gold life ".Prepared rhizome of rehmannia, to use, is altogether the product for yin-nourishing of enriching blood with tuber of dwarf lilyturf mutual reinforcement between.The white return lung warp of fritillaria thunbergii color, has The work(of reducing phlegm and resolving masses, priming enter lung network, mop up that phlegm is turbid, and assistant helps prodrug further to recover the normal physiological function of lung network.Processed in side Radix glycyrrhizae relieving spasm to stop pain, coordinating the drug actions of a prescription, it is to make medicine.

All medicines share, treating a disease by looking into both its root cause and symptoms, tonification and purgation in combination, and supplementing qi and nourishing yin, promoting blood circulation, eleminating phlegm and freeing channels share, up to qi-restoratives dredging collateral Effect.

Compared with prior art, the present invention has the advantages that.

The oral medicinal herb preparation of idiopathic pulmonary fibrosis is treated made of pure Chinese medicine by present invention system, is managed in Traditional Chinese Medicine By under guidance, the pathogenesis of idiopathic pulmonary fibrosis " deficiency syndrome of the lung network stasis of blood " is recognized according to veins disease theories, based on qi-restoratives dredging collateral Principle of reatment, allotment supplementing qi and nourishing yin, Chinese medicine promoting blood circulation and removing blood stasis, eliminating the phlegm dredging collateral, for treating idiopathic lung pulmonary fibrosis.

Compatibility of the present invention is proper, curative for effect, medication is simple, safe, compliance is good, medical treatment cost is more low excellent Point.Compared to existing medicine, the present invention is delaying progression of disease, improves life in patients and is avoiding poisonous side effect of medicine etc. Also there is certain advantage, to treat the preferable compound Chinese medicinal preparation of idiopathic lung fiber curative effect.

The present invention can be combined with hormone, associated with therapeutic effect better than using hormone merely, so as to reduce hormone pair In the side effect of human body, there is preferable application prospect.

Brief description of the drawings

Fig. 1 is that each group HE dyes picture in embodiment 1（× 200 times）.

Fig. 2 is that each group Masson dyes picture in embodiment 1（× 200 times）.

Fig. 3 is INF- γ mRNA expression electrophoretograms in each group lung tissue of rats in embodiment 1, wherein, 1. blank pair According to group；2. model control group；3. Western medicine group；4. astragalus root+pseudo-ginseng group；5. astragalus root+wide dragon group；6. the red sage root+Ligusticum wallichii group；7. Astragalus root+red sage root group.

Fig. 4 is IL-4 mRNA expression electrophoretograms in each group lung tissue of rats in embodiment 1, wherein, 1. blank controls Group；2. model control group；3. Western medicine group；4. astragalus root+pseudo-ginseng group；5. astragalus root+wide dragon group；6. the red sage root+Ligusticum wallichii group；7. process The Radix Astragali+red sage root group.

Fig. 5 is preparation flow schematic diagram of the present invention.

Embodiment

The monarch drug in a prescription screening experiment of the present invention of embodiment 1.

Experimental basis：This compound preparation inventor is with CBMdisc（CBM）, middle National IP Network（CNKI） Database is scope, using a variety of data digging methods, determines that medicine uses in Chinese medicine compound prescription preventing and treating idiopathic pulmonary fibrosis side The frequency first five be the Radix Astragali, the red sage root, radix glycyrrhizae, the tuber of dwarf lilyturf, Ligusticum wallichii, core combines first five red sage root-Radix Astragali, the red sage root-Radix Angelicae Sinensis, pellet Ginseng-Ligusticum wallichii, the Radix Astragali-pseudo-ginseng, the red sage root-Radix Codonopsis, card element are mainly that the deficiency of vital energy, blood stasis, the deficiency of Yin are most commonly seen, and its card type often to demonstrate,prove more Based on element is mutually combined.Based on data above Result, the application patent side monarch drug in a prescription astragalus root+wide dragon and astragalus root are determined + the red sage root, the red sage root+Radix Angelicae Sinensis, the Radix Astragali+pseudo-ginseng, model group, six groups of prednisone are compared, and are injected with the most frequently used tracheotomy Bleomycin modeling mode is observed.

Experiment purpose：Inquire into various combination compound Chinese medicinal preparation monarch drug in a prescription and intervene idiopathic pulmonary fibrosis rat model effect effect Should, it was demonstrated that astragalus root+wide dragon combined effect is optimal.

Materials and methods

1. material

1.1 experimental animal

From Wistar rats 210, male and female half and half, 200 ± 20g of body weight, cleaning grade, to be purchased from the long-living biotechnology in Liaoning limited Company（Animal credit number：SCXK (the Liao Dynasty) 2010-0001）

1.2 experimental drugs and reagent

Experimental drug：Hydrochloride for injection bleomycin（Nippon Kayaku K. K, production approval number X30362, import drugs Registration certificate number：H20090885,15mg/ branch）；Chinese medicine each group（By Affiliated Hospital of Liaoning University of Traditional Chinese Medicine's experiment of TCM center system Agent room provides.Concentration:1.13g/ml；Date is provided：2016.9.04.Specification：500ml/ bottles；Preservation condition：4 DEG C of refrigerators are protected Deposit）；(Tianjin Tianyao Pharmaceutical Co., Ltd. produces prednisone acetate tablets, and state is accurate：H12020698 batch numbers：130302, 5mg/ pieces).

Reagent：IL-4 ELLISA kits（Article No.：EK0406）, INF- γ ELLISA kits（Article No.：EK0374）、 Protein Ladder (11 band)（Article No.：00150801）:Thermo companies of the U.S.；Western Bright ECL luminescent solutions （Article No.：D-26012-407）：Advansta companies of the U.S.；Total RNA extraction reagent box（Centrifuge column type）：TIANGEN BIOTECH （BEIJING）；BioRT reverse transcription amplifications（RT-PCR）Kit（Two-step method）：Beijing Quanshijin Biotechnology Co., Ltd； DNA marker (article No.s：BM101) Beijing Quanshijin Biotechnology Co., Ltd；Trizol：Invitrogen companies；Primer, Polygala Bioisystech Co., Ltd is won on behalf of synthesizing by Beijing three.

Instrument

CX41-12C02 light microscopes (Japanese Olympus companies), DYCP-40E electrophoresis tanks（Liuyi Instruments Plant, Beijing）, Tanon Gis gel image analysis systems（Shanghai Tian Neng Science and Technology Ltd.s）, BI-2000 type image analysis systems（Chengdu is safe Science and Technology Ltd. of alliance）, the full-automatic ELIASA of the types of anthos 2010（Austrian AnthosLabtecInstruments）, WD-9413B type gel image analysers（Beijing Liuyi Instrument Factory）, the spectrophotometer of 16C14 types 721（Shanghai precision section Learn Instrument Ltd.'s manufacture）, UV-2800 type ultraviolet-uisible spectrophotometers（You Nika（Shanghai）Instrument Co., Ltd）； EPS300 type electrophoresis apparatuses（Shanghai Tian Neng Science and Technology Ltd.s）, grads PCR instrument（Bio Rad Laboratories）, transferring film instrument（Shanghai day energy Science and Technology Ltd.）.

Method

210 Wistar rats conventinal breedings of 2.1 animal packets and administration are randomly divided into seven groups after 3 days by male and female, body weight, Respectively blank control group, model control group, prednisone acetate tablets control group (abbreviation Western medicine group), astragalus root+wide dragon, process Huang Stilbene+the red sage root, the red sage root+Radix Angelicae Sinensis, six groups of the Radix Astragali+pseudo-ginseng, every group 30.Modeling next day, day gastric infusion, its Chinese and Western medicine group gives With Econopred piece 0.625mg, suspension is dissolved into distilled water, according to 1ml/100g volume gavages.Dosage of drug group Give 0.5g dosage respectively, after distilled water dissolved particles agent, also by 1ml/100g volume gavages.Blank control group and model pair Give isometric physiological saline respectively according to group, each group checks weekly weight, adjusts dosage according to changes of body mass, altogether 28 days.

Modeling method is with reference to Szapiel etc.^[1]Method is big with 3% yellow Jackets (40mg/kg) intraperitoneal injection of anesthesia Mouse, the imperial mixture granule group difference tracheal strips Injecting Bleomycin after Retaining solution 0.2-0.3ml of model group, metacortandracin group, ginseng (press constitution Measure 5mg/kg administrations), under equal conditions intratracheal injection etc. holds physiological saline to Normal group.

Methods of sample collection tri- time point materials of the 7th, 14,28 d, each time point each component after modeling Other 10 rats of abdominal aorta sacrificed by exsanguination.After each group rat is to be injected intraperitoneally 10% chloral hydrate anesthesia, fixation of being lain on the back, Through abdominal aortic blood 4-5ml, at room temperature after static 2h, centrifugation（3600r/min, 10min）, separate serum, be sealed in- 80 DEG C of refrigerators, it is to be measured；Then turn on thoracic cavity isolated lung tissue.After 4 DEG C of physiological saline rinsed cleans, connective tissue is rejected, with Filter paper blots, and claims weight in wet base.Left and right lung tissue is separated again, takes left lung tissue to be placed in 10% neutral buffered formalin solution fixed, Conventional dehydration, with FFPE.Then will take in the cryopreservation tube that right lung tissue is put into sterilization in advance and DEPC is treated, -80 DEG C Under the conditions of save backup.

Method is detected and judged by ELISA kit explanation operation.Each hole is determined under 450nm wavelength with ELIASA selection Absorbance（OD）Value.

2.5Western blot methods are detected and judged

After each group lung tissue of rats carries out tissue homogenate, total protein is extracted with Tissue lysates, and it is dense to carry out BCA methods measure albumen Degree.After each group protein sample carries out SDSPAGE electrophoresis with 40 μ g albumen applied sample amounts, by electrotransfer by protein delivery to pvdf membrane On.Pvdf membrane carries out primary antibody incubation (1: 500) after the closing overnight of 5% BSA/PBS solution, with INF- γ, IL-4, further After being incubated with the secondary antibody of HRP marks, protein signal is detected using DAB development processes.Using biogel electrophoretic image analysis system It is scanned and quantifies, calculates each purpose band and relative amount of the internal reference β-actin Reinhoit Zahl as each albumen.

Detection and judgement are surveyed by TRIzol liquid specification operation extraction lung tissue total serum IgE with ultraviolet specrophotometer Measure RNA concentration and quantify, template amount takes 2 μ L.Primer：IFN-γ：Upstream：Under 5 '-TGGATATCTGGAGGAACTGG-3 ' Trip：5 '-CGACTCCTTTTCCGCTTCCT-3 ' amplified fragments 310bp；IL-4 primers：Upstream 5 '- - CTTTCAGTGTTGTGAGCTT-3 ' the amplified fragments 360bp of CACCTTGCTGTCACCCTGT-3 ' downstreams 5 '；β-actin draw Thing：- AATGTCACGCACGATTTCCC-3 ' the amplified fragments of-GAGACCTTCAACACCCCAGCC-3 ' the downstreams of upstream 5 ' 5 ' 263bp.Reaction condition：Pre-degeneration 2min, circulation：94 DEG C of denaturation 30s, 65 DEG C of 30 s of annealing, 72 DEG C extend 30s, 72 DEG C of ends Extend 30s, 30 circulations.The hot lid design temperature of PCR amplification instrument is 105 DEG C.RT-PCR product decision analysises：RT-PCR products exist Electrophoresis is carried out on 1.5% Ago-Gel, sample-adding amount is 5 μ L, using Tanon Gis gel image analysis system measurement electrophoresis Band integrated absorbance, (IA) are determined, and analyze the IA ratios of each purpose RNA bands and internal reference β-actin RNA bands, as Each purpose RNA relative amount.

Statistical analysis technique statistical analysis handles software using SPSS 15.0, and measurement data data are added and subtracted with mean and marked It is accurate poor（±s）Represent, two groups are compared and examined with t；Multiple-group analysis variance analysis, p<0.05 or p<0.01 is considered as statistically With significant.

As a result

1. ordinary circumstance

During experiment, 10 rats deaths, the death rate 4.7% are shared.Wherein on the day of modeling, blank control group has 1 rat Death, laparotomy exploration is without exception, considers that overdose of anesthesia is dead.3d model control groups, astragalus root+wide dragon group, Western medicine group are equal There is 1 rats death, 5d astragalus roots+pseudo-ginseng group, Western medicine group also have 1 rats death, and 5 equal bodies of rat of appeal are become thin, The most thin underweight 130g of person, and snout has a small amount of bronzing secretion, consulting literatures, considers the cell toxicant with bleomycin Property is relevant, or Earlier period of inflammation is heavier, and immunity difference is not resistant to.15d model control groups, Chinese medicine astragalus root+pseudo-ginseng group have 1 Rats death, 17d, 24d salviamiltiorrhizabung+Ligusticum wallichii group respectively have a rats death, in view of rat is dead at night, after dissection Detect, do not find obvious exception, the analysis cause of the death may be relevant with weary oxygen or respiratory failure.

Induced lung index variation situation

Compared with blank control group：Remaining six groups of rat paragonimus cysts through bleomycin modeling are obvious in 3 detection time points Increase（p<0.01）；Compared with model control group：Western medicine group, astragalus root+pseudo-ginseng group, astragalus root+wide dragon group rat paragonimus cyst Substantially reduced in 3 detection times（p<0.01), the red sage root+Ligusticum wallichii, astragalus root+red sage root group then decreased 14d, 28 days； Compared with Western medicine group：Astragalus root+wide dragon group rat paragonimus cyst is decreased obviously（p<0.05 or p<0.01）(being shown in Table 1)

3. model evaluation

3.1 HE are dyed

Blank control group lung tissue of rats is clear in structure, and alveolar septum has no hyperemia, oedema, inflammation and fibrosis, respectively without thickening Time point does not occur obvious pathological change.

Model control group meets pulmonary fibrosis pathological change, shows as pulmonary alveolitis and pulmonary fibrosis.7d using pulmonary alveolitis as It is main, visible pulmonary capillaries hyperemia is dyed, alveolar septum oedema, alveolar wall has thickened, and it is thin to occur a large amount of macrophages in alveolar space Inflammatory cell infiltration based on born of the same parents, and visible a small amount of fibroblast proliferation aggregation；14th day, pulmonary alveolitis mitigated earlier above, Alveolar septum is obvious broadening earlier above, and inflammatory cell has been reduced, and fibroblast then showed increased earlier above, interstitial collagen fiber Start hyperplasia, begin with fibrosis change；28th day, pathological manifestations were based on fibrosis.Pulmonary alveolitis disappears substantially, rarely seen a small amount of Inflammatory cell, alveolar collapse, disappearance, structural change, alveolar septum further thickens, is broken, a large amount of fibroblasts aggregations, Collagen deposition, pulmonary fibrosis form fibrotic scar based on changing.Compared with model control group, the lung of remaining five groups of administration groups Histopathology is similar, but has different degrees of improvement, and pathological change is similar, and lesion degree is sequentially respectively from light to heavy：The During 7d, Western medicine group, astragalus root+wide dragon, astragalus root+pseudo-ginseng, Radix Angelicae Sinensis+Ligusticum wallichii, the astragalus root+red sage root；During 14d：Western medicine group, process The Radix Astragali+wide dragon, astragalus root+pseudo-ginseng, Radix Angelicae Sinensis+Ligusticum wallichii, the astragalus root+red sage root；During 28d：Astragalus root+wide dragon, Western medicine group, process The Radix Astragali+pseudo-ginseng, Radix Angelicae Sinensis+Ligusticum wallichii, the astragalus root+red sage root（See Fig. 1）.

3.2 Masson are dyed

After dyed, nucleus is in blue-green, and cytoplasm and gtelatinous fibre take on a red color, and collagenous fibres are in green.

Blank control group bronchus of rat wall collagen layer is relatively thin, and alveolar septum portion has a small amount of very thin collagen of blueness of dying to divide Cloth, and thin vessels, bronchium have no.Model control group rat meets pulmonary fibrosis pathological change, the glue compared with other each groups Fibrillation deposition is most heavy.It is broadening between rat 7d alveolars, it is seen that bronchial wall, vascular wall and alveolar septum are had illicit sexual relations au bleu Collagenous fibres distribution；There are collagenous fibres in the visible bronchuses at different levels of 14d and vessel outer wall, the alveolar septa thickened, prompt Collagenous fibres increase, extracellular matrix increase；28d can in part bronchiole, low externa and fibrosis consolidation area See large stretch of blue collagen fiber hyperplasia, prompt diffusivity lung fiber to be formed.Compared with same period model control group, remaining five groups of administrations Group Each point in time pathological change is similar, but fibrosis have a different degrees of improvement, and lesion degree is suitable from light to heavy Sequence：Western medicine group, astragalus root+wide dragon, astragalus root+pseudo-ginseng, Radix Angelicae Sinensis+Ligusticum wallichii, the astragalus root+red sage root during 7d；During 14d, Western medicine Group, astragalus root+wide dragon, astragalus root+pseudo-ginseng, Radix Angelicae Sinensis+Ligusticum wallichii, the astragalus root+red sage root；Astragalus root+wide dragon, Western medicine during 28d Group, astragalus root+pseudo-ginseng, Radix Angelicae Sinensis+Ligusticum wallichii, the astragalus root+red sage root（See Fig. 2）.

Hydroxyproline content measurement result in each group lung tissue of rats

Compared with blank control group：Model control group, Western medicine group, astragalus root+pseudo-ginseng group, astragalus root+red sage root group rat are in 3 inspections Survey the equal showed increased of hydroxyproline in time point lung tissue（P<0.01）, astragalus root+wide dragon group also has increase, but without statistics Difference（P>0.05）；Compared with same period model group, Western medicine group, astragalus root+three, astragalus root+wide dragon group rat are when detecting for 3 Between put lung tissue in hydroxyproline significantly reduce（P<0.01 or P<0.05）Though the red sage root+Ligusticum wallichii, astragalus root+red sage root group also have Reduced, but difference unobvious（P>0.05）；Compared with Western medicine group：Astragalus root+wide dragon group rat hydroxyl in the 7th day lung tissue Proline reduces obvious（P<0.05）（It is shown in Table 2）.

Method each group rat blood serum INF- γ, IL-4 assay result

3.1 each group rat blood serum INF- γ content

Compared with blank control group, the INF- γ of other each group rat blood serums substantially reduce in 3 periods（P ＜ 0.01）； Compared with model control group, the INF- γ of Western medicine group, astragalus root+pseudo-ginseng group and astragalus root+wide dragon group rat blood serum are at 3 Between section it is significantly raised（P ＜ 0.01 or P ＜ 0.05）, INF- γ are 14 in the red sage root+Ligusticum wallichii, astragalus root+red sage root group rat blood serum My god, raised within 28 days（P ＜ 0.05）；Compared with Western medicine group：Astragalus root+wide dragon, astragalus root+equal difference of pseudo-ginseng group are without system Meter learns meaning（P ＞ 0.05）, the INF- γ of astragalus root+pseudo-ginseng group, astragalus root+red sage root group rat blood serum are obvious at 28 days to be reduced（P ＜ 0.01）, in 7 days, 14 days equal no significant differences（P ＞ 0.05）.（It is shown in Table 3）

3.2 each group rat blood serum IL-4 assay result

Compared with blank control group, model control group, astragalus root+pseudo-ginseng group and the red sage root+Ligusticum wallichii, astragalus root+red sage root group rat serum Clear IL-4 is significantly raised in 3 periods（P ＜ 0.01 or P ＜ 0.05）；Compared with model control group, Western medicine group, process The IL-4 of the Radix Astragali+pseudo-ginseng group, astragalus root+wide dragon group, the red sage root+Ligusticum wallichii, astragalus root+red sage root group rat blood serum is in 3 periods It is obvious to reduce（P ＜ 0.01）；Compared with Western medicine group：The IL-4 of astragalus root+pseudo-ginseng group, astragalus root+wide dragon group rat blood serum In 3 period no significant differences（P ＞ 0.05）.（It is shown in Table 4）

4. each group lung tissue of rats INF- γ/IL-4mRNA expressions

4.1RT-PCR methods detection each group lung tissue of rats INF- γ mRNA expression results are shown：With blank control group ratio Compared with remaining each group lung tissue of rats INF- γ mRNA significantly lowers in 3 period expressions（p<0.01）；With model pair Compare according to group, Western medicine group, Chinese medicine each group lung tissue of rats INF- γ mRNA significantly raise in 3 period expressions（p< 0.01）.Compared with Western medicine group, astragalus root+wide dragon group lung tissue of rats INF- γ mRNA show in 3 period expressions Write and lower（p<0.01）（It is shown in Table 5, Fig. 3）

4.2 each group lung tissue of rats IL-4 mRNA expressions

RT-PCR methods detection each group lung tissue of rats IL-4 mRNA expression results are shown：Compared with blank control group, remaining Each group lung tissue of rats IL-4 mRNA significantly raise in 3 period expressions（p<0.01）；Compared with model control group, Western medicine group, Chinese medicine each group lung tissue of rats IL-4 mRNA significantly lower in 3 period expressions（p<0.01）.With Western medicine Group compares, and astragalus root+wide dragon group lung tissue of rats IL-4 mRNA are suitable with Western medicine in 3 period expressions（It is shown in Table 6, Fig. 4）.

This experimental studies results shows that INF- γ, IL-4 in blank control group rat blood serum are during experiment without obvious Change.In contrast, INF- γ contents substantially reduce in model control group rat blood serum, and IL-4 contents substantially increase and In fibrotic processes, the increase of both contents is just opposite with downward trend.Illustrating two then has obvious antagonism, with Document report result is consistent.In each group through pharmaceutical intervention, compared with model control group, Western medicine and rat in each dosage group of Chinese medicine Serum I NF- γ levels substantially raise, and IL-4 levels then substantially reduce, and prompt medicine to have and promote INF- γ, suppress IL-4's Effect.It of particular concern is, Western medicine group and the content and blank control group ratio of IL-4 in astragalus root+wide dragon group serum Compared with though there is rise, not possessing both statistical significances, prompting has the function that significantly to suppress IL-4 in serum.And process The Radix Astragali+wide dragon is slightly better than Western medicine group to INF- γ, IL-4 expression regulation effect.Pass through relative immunity group, RT-PCR methods IL-4, INF- γ albumen and mRNA testing results in the lung tissue of rats measured, astragalus root+wide dragon effect are slightly better than Western medicine Group, remaining each group are worse than Western medicine group.

The experimental study of the preparation method extracting factor of the present invention of embodiment 2

1st, factor level table

In order to select optimal water extraction process, using orthogonal experiment to influenceing the principal element extraction time of water extraction, carrying Number, amount of water is taken to be investigated, each factor selects three levels, and concrete numerical value is shown in Table 1.

, test method and data

Get it filled material（Astragalus root 30g, radix glehniae 20g, Radix Angelicae Sinensis 15g, Ligusticum wallichii 15g, prepared rhizome of rehmannia 15g, earthworm 15g, honey-fried licorice root 15g, Reticulate millettia 15g, tuber of dwarf lilyturf 15g, fritillaria thunbergii 15g）Every part of 170g, totally nine parts, according to factor level table and L₉（3⁴）Orthogonal arrage is tried Test.Every part of extract solution is concentrated, is transferred in 250ml measuring bottles, is added water constant volume, shake up, precision draws 15ml, 70 DEG C of dryings, obtains Dry cream, using Astragaloside IV and Calycosin-7-O-BETA-D-glucoside content and dry cream rate as inspection target, carry out overall merit (dry cream rate, hair Stamen isoflavones glucoside content, the weight coefficient of Astragaloside content are respectively 0.2,0.4,0.4) preferred optimum extraction work Skill, concrete outcome are shown in 2.

, variance analysis

Orthogonal experiments are subjected to variance analysis, the results are shown in Table 3.

From table 2,3 results, B factors are significant factors, and it is B ＞ C ＞ A that each factor influences primary and secondary to result, optimum extraction Technique is A₃B₃C₃, it is cost-effective with reference to big produce reality, with A₁B₃C₁As optimum extraction process, i.e., plus 6 times of water is measured, extraction 3 It is secondary, extract 1 hour every time.

, confirmatory experiment：

Get it filled material 170g, totally three parts, is operated by process above, measure Astragaloside IV and calycosin glucoside content, goes out Cream rate.Checking test the results are shown in Table 4.

As a result show, water extraction process is stable, favorable reproducibility.

The experimental study of the preparation method separation and purification technique of the present invention of embodiment 3.

Chinese medicine extract is the mixture of Multiple components, and existing active ingredient has invalid impurity again, if do not removed impurity, meeting Influence the quality and stability of preparation.This prescription removes a part of impurity using sedimentation separation method.Specific method is by extract solution After the standing refrigeration of certain time, Aspirate supernatant, precipitation is discarded.To extract concentration, time of repose, dwell temperature is done Investigate.

1st, extract concentration is investigated

Medicinal material is weighed in prescription ratio, is decocted by above-mentioned technique, filtration, filtrate is concentrated into 0.5g crude drugs/ml, 1.0g crude drug/ml, 1.5g crude drugs/ml, respectively take 100ml, and into graduated cylinder, normal temperature stands 24 hours, and as a result 0.5g crude drugs/ml groups sedimentation is obvious, solid-liquid Layering is clear, and 1.0g crude drugs/ml groups sedimentation is obvious, and solid-liquid layering is substantially clear, and 1.5g crude drugs/ml groups have sedimentation, but not complete Complete to be sink to graduated cylinder bottom, color is deep, solid-liquid layering unobvious, is unfavorable for supernatant sucking-off.Therefore extract solution is concentrated into 0.5g Crude drug/ml is settled, proper.

2nd, time of repose is investigated

It is 0.5g crude drugs/two parts of ml 100ml to take concentration, and respectively into graduated cylinder, normal temperature stands 24 hours, 48 hours, and observation is heavy Form sediment, as a result stand 48 hours precipitations compared with standing 24 hours precipitations, have no showed increased, so extract solution stands 24 hours .

3rd, dwell temperature is investigated

It is 0.5g crude drugs/two parts of ml 100ml to take concentration, and respectively into graduated cylinder, a room temperature, portion is put in refrigerator and refrigerated （4℃）24 hours, as a result precipitation capacity and no significant difference.But to prevent decoction from going bad, put refrigerator cold-storage and be preferred.

4 clinical test of the present invention of embodiment

Purpose：Evaluation present invention treatment IPF clinical efficacy

1. clinical data：

1.1 case sources and packet

This research observation case meets the case of inclusion criteria, selection from Affiliated Hospital of Liaoning University of Traditional Chinese Medicine's outpatient service and ward Morbidity 3 years in early metaphase pulmonary interstitial fibrosis patient, altogether observe patient IPF 60；According to randomly assigne, using random digit Table method, test group and each 30 of control group are randomly divided into, and according to double blinding（Researcher and subject）Envelope is hidden principle and is divided into Herb mixture+hormone prednisone treatment group and hormone prednisone group.

1.2 experiment medications

Chinese medicine compound prescription mixture（There is provided by Affiliated Hospital of Liaoning University of Traditional Chinese Medicine's experiment of TCM center Drug Manufacturing Room.Concentration:1.13g/ ml；Date is provided：2016.9.04.Specification：500ml/ bottles；Preservation condition：4 DEG C of refrigerators preserve）.Main prescription and preparation method are as follows：

1.2.1 prescription：132 parts of astragalus root, 66 parts of wide dragon, 88 parts of radix glehniae, 66 parts of Radix Angelicae Sinensis, 66 parts of Ligusticum wallichii, prepared rhizome of rehmannia 66 Part, 66 parts of honey-fried licorice root, 66 parts of reticulate millettia, 66 parts of the tuber of dwarf lilyturf, 66 parts of fritillaria thunbergii

1.2.2 preparation method：The taste of the above ten, fritillaria thunbergii are given as one thinks fit cataclasm, add 6 times of amount decoctings to boil 3 times, 1 hour every time, collecting decoction, filter Cross, be concentrated into 1500ml, refrigerate（4 DEG C~10 DEG C）Place 24 hours, take supernatant concentration to be dispensed, sterilizing, i.e., to 1000ml .

1.3 administrated method

Test group（A groups）：Taken 2 days by every pair of decoction of medicinal ingredients of formula, twice daily, early to take 50ml within 30 minutes before meals, supper is later half Hour takes 50ml, heats decoction before taking；During taking decoction of medicinal ingredients, forbid taking pungent, fish raw meat, stimulating food, raw food, it is greasy, Sour and astringent F＆B, the course for the treatment of 3 months, oral one month of joint prednisone 0.5mg/kg, rear 2 months prednisones are changed to 0.25mg/kg.Hormone group（B groups）：Oral one month of prednisone 0.5mg/kg, rear 2 months prednisones are changed to 0.25mg/kg.

1.4 diagnostic criteria：

1.4.1 case selection standard

Western medicine diagnostic criteria（With reference to respirology branch of Chinese Medical Association idiopathic lung（Interstitial）Fibrosis diagnoses and treatment guidelines （Draft）；Chinese tuberculosis and breathing magazine 2002；（25）, 7：387.）Patient immune function is normal, and meets following all masters Want conditions for diagnostics and at least 3~4 secondary conditions for diagnostics, can clinical diagnosis be IPF.

Main Diagnosis standard：The cause of disease of known interstitial lung disease except 1., toxic action, environmental pollution such as some drugses With the ILD caused by connective tissue disease；2. abnormal PFT changes, including restrictive ventilatory functional disturbance and (or) gas Exehange barrier；3. chest HRCT shows as the netted shade in bilateral pulmonary bottom, few to change with ground glass sample, there is honeycomb lung in late period； 4. the evidence of TBLB or bronchoalveolar lavage without other diseases.

Secondary diagnostic criteria：1. the age>50 years old；2. had difficulty in breathing after concealment onset or unaccountable motion；3. disease Sick duration >=3 month；4. bilateral pulmonary bottom audible and inspiratory crackles.

Severity Scaling standard

Weight：TLC (total lung capacity) or DLco (diffusion)≤40%；Or pulmonary function detection can not be completed；

In：40%<TLC (total lung capacity) or DLco (diffusion)≤60%；

Gently：60%<TLC (total lung capacity) or DLco (diffusion)≤80%；

Nothing：80%<TLC (total lung capacity) or DLco (diffusion).

Traditional Chinese medical science lung kidney qi Yin bivacuity, blood stasis retardance card diagnostic criteria：（With reference to Issued by China State Bureau of Technical Supervision《Tcm clinical practice Diagnosis and treatment term syndrome part》With《New Chinese medicine clinical guidance principle》Formulate：(1) chronic cough, phlegm are white;(2) dyspnea with shortness of breath, it is dynamic then breathe heavily Very, air-breathing is especially difficult;(3) uncomfortable in chest, weak (4) easily catch a cold;(5) soreness and weakness of waist and knees, Hiccough and deaf, dizzy (6) tongue it is dark red or There is ecchymosis, deficient and weak pulse or the thin chi that sinks are weak.Possess 3 i.e. diagnosable (wherein 1,2,6 is indispensable symptom).

1.4.2 include and exclusion standard

Inclusive criteria：

Meet idiopathic pulmonary interstitial fibrosis Western medicine diagnostic criteria；The course of disease is less than 3 years；Age was in 50 to 70 years old persons；In two weeks not Took the medicine for having considerable influence to experiment medication.

Exclusion standard：Merge the heart, brain, lung, liver, kidney and hemopoietic system severe primary disease, and psychiatric patient； The gestational period or nursing period patient, and to testing medication allergy sufferers；Other researchers are participated in nearly two months；Refusal can not be signed Affix one's name to informed consent form person.

1.4.3 efficacy assessment standard

Branch is breathed according to Chinese Medical Association to formulate for 2002《Idiopathic lung (interstitial) fibrosis diagnoses and treatment guidelines (grass Case)》Formulate

1.4.4 doctor trained in Western medicine the standard of curative effect evaluation

After the treatment of 3 months, if follow-up twice in succession meets following 2 conditions above, then it is assumed that to therapeutic response Well, the state of an illness improves:1. symptom mitigation, mobility enhancing.2. x-ray rabat or HRCT abnormal images are reduced.3. PFT table Existing TLC, VC, DLCO, PaO2 long period keeps stable.Data below is for reference:TLC or VC increases >=10%, or at least increase ≥200 mL;DLCO increases >=15% at least increase by 3 mLmin-1mmHg-1;Arterial oxygen saturation (SaO2) increases Add ＞ 4%;PaO2 increases >=4 mmHg (thinking lung improving physiological function with 2 or more than 2 persons) in cardiopulmonary exercise test.

Low Response or Endodontic failure:1. exacerbation of symptoms, particularly have difficulty in breathing and cough.It is 2. different on x-ray rabat or HRCT Normal image increases, and honeycomb lung or pulmonary hypertension sign particularly occurs.3. PFT deteriorates.Data below is for reference:TLC Or VC declines >=10% or declines >=200 mL;DLCO declines >=15% or at least declines >=3 mLmin-1mmHg-1; SaO2 decline alveolar-arterial partial pressure of oxygen poor ［ P (A-a) O2 ］ in >=4%, or exercise test increase >=4 mmHg (with 2 or More than 2 persons think that PFT deteriorates).

It is stable：After treatment 3 months, symptom and x-ray rabat or HRCT show interstitial lung lesion without significantly improving or aggravate.

1.4.5 tcm syndrome curative effect determinate standard：

Judged according to Nimodipine method integration method, computational methods：Therapeutic index=（Integrated before treatment after integration-treatment）/ treat preceding integrate × 100%

1. clinic control symptom, sign disappear or basic disappearance, syndrome integral Jian Shao≤95%

2. effective symptom, sign are obviously improved, the ＜ 95% of syndrome integral Jian Shao≤70%

3. effective symptom, sign take a favorable turn, the ＜ 70% of syndrome integral Jian Shao≤30%

4. invalid symptom, sign are not improved, even aggravating, syndrome integral reduces ＜ 30%

1.5 evaluation index：

1.5.1 safety indexes

1. general record project：

Test start date, informed consent form sign date, the past medication, with disease etc..

Demographic characteristics：Sex, age, height, body weight, nationality.

Vital sign：Body temperature, tranquillization pulse frequency, breathing, rest 10 minutes after blood pressure（Systolic pressure, diastolic pressure）.

Influences on curative effect：Allergies, medication history, ill history, drug combination situation.

Observation on compliance：Can on time, medication according to quantity；Whether other medicines are voluntarily used.

2. blood, urine, feces are conventional, electrocardiogram, liver function（ALT、AST）, renal function（BUN、Cr）Detection, x-ray rabat, blood coagulation Mechanistic assays, gait test in 6 minutes.

3. adverse reaction

1.5.2 clinical effect index

1. clinical symptoms：Cough, expiratory dyspnea, gait test in 6 minutes.

2. the Syndrome Scale of traditional Chinese medical science lung kidney qi Yin bivacuity and blood stasis retardance card quantifies.

TCM symptom score standard：（With reference to《New Chinese medicine guideline of clinical investigations》）

Pant：Weight (6 points)：Failing to lie flat due to dyspnea when quiet；In (4 points)：Pant and do not write when quiet, aggravated after pausing activity； Gently (2 points)：Panted after obvious activity (such as stepping on building, work)；Without (0 point)：Unconsciously panted after activity.

Feel suffocated：Weight (6 points)：Being felt suffocated when quiet to lie down；In (4 points)：Feel suffocated and do not write when quiet, add after pausing activity Weight；Gently (2 points)：Obvious activity (such as stepping on building, work) is slightly felt suffocated afterwards；Without (0 point)：Unconsciously felt suffocated after activity.

It is uncomfortable in chest：Weight (6 points)：It is uncomfortable in chest serious when quiet；In (4 points)：It is uncomfortable in chest when quiet not write, aggravated after pausing activity； Gently (2 points)：Obvious activity (such as stepping on building, work) is slight uncomfortable in chest afterwards；Without (0 point)：It is unconsciously uncomfortable in chest after activity.

Shortness of breath：Weight (6 points)：Shortness of breath must not continue when quiet, it is impossible to lie down；In (4 points)：Shortness of breath does not write when quiet, pauses Aggravated after activity；Gently (2 points)：Obvious activity (such as stepping on building, work) slight shortness of breath afterwards；Without (0 point)：Gas is can not help after activity It is short.

Cough：Weight (6 points)：Cough is frequent round the clock, influences work and sleep；In (4 points)：Paroxysmal cough, do not influence to sleep；Gently (2 points)：Interruption cough；Without (0 point)：Without cough.

Cough up phlegm：More (3 points)：24h amounts of expectoration are in 100 more than mL；In (2 points)：The mL of 24h amounts of expectoration 50~100；Gently (1 point)： Occasionally there are phlegm, the mL of 24h amounts of expectoration 20~50；Without (0 point)：Without phlegm

Velcros sounds：More (6 points)；The full portion of two lungs；In (4 points)：Double lungs are dispersed in Velcros sounds；Gently (2 points)：Side lung audible And；

Without (0 point)：Double lungs fail hear and.

Moist rales：More (6 points)；The full portion of two lungs；In (4 points)：Double lungs are dispersed in moist rales；Gently (2 points)：Side lung audible And；Without (0 point)：Double lungs fail hear and.

Dry rales：More (6 points)；The full portion of two lungs；In (4 points)：Double lungs are dispersed in dry rale；Gently (2 points)：Side lung audible And；Without (0 point)：Double lungs fail hear and.

Soreness and weakness of waist and knees：Weight (6 points)：Have always；In (4 points)：Through conventional；Gently (2 points)：Have once in a while；Without (0 point)：Never Have.

Blood-stained sputum：Have（2 points）：There is the trace of blood in phlegm.Nothing（0 point）：Without the trace of blood in phlegm.

Heating：Have（2 points）：Body temperature is more than 37.5.Nothing（0 point）：Body temperature is below 37.4.

Pharyngalgia：Have（2 points）：There is pharyngalgia；Nothing（0 point）：Without pharyngalgia.

Sweating：Have（2 points）：When have sweating；Nothing（0 point）：Without sweating

Dry：Have（2 points）：Feel dispute pharyngoxerosis；Nothing（0 point）：Without dispute pharyngoxerosis

It is tired：Have（2 points）：Feel obvious lassitude and weak；Nothing（0 point）：Without lassitude and weak

It is nervous：Have（2 points）：Feel and have palpitation, it is obvious after activity；Nothing（0 point）：Without nervous

Thirst with desire to drink：Have（2 points）：Pharyngoxerosis is obvious；Nothing（0 point）：Without pharyngoxerosis

Lip is purple dark：Have（2 points）：Lip is purple dark obvious；Nothing（0 point）：It is purple dark without lip

Onyx is purple dark：Have（2 points）：Onyx is purple dark obvious；Nothing（0 point）：Flukeless gentian violet is dark

Acropachia：Have（2 points）：There is obvious acropachia；Nothing（0 point）：Without acropachia

Tongue picture：There is exception（2 points）Secretly, it is fat, Tai Bai or Huang etc.；It is without exception（0 point）Pink tongue, thin and whitish fur.

Pulse condition：There is exception（2 points）Sink sliding etc.；It is without exception（0 point）Imaginary number.

3. physical and chemical index：PFT：Ventilatory function detects, lung capacity（FVC、VC）, residual volume(RV)（RV）, total lung capacity（TLC） Or the change of diffusing capacity of the lungs for carbon monoxide (DLco)；Blood gas analysis：PCO2、SaO2、PaO2 ；Gait test in six minutes；TGF- β, IL-4, IL-13, IL-12, IFN-γ measure.

1.6 statistical analysis

Compare two-by-two between measurement data sample average and χ is used using variance analysis, the statistical analysis of grouped data²Examine, with α =0.05 is inspection level, and P ＜ 0.05 think that difference is statistically significant.This testing data is entered using the software kits of SPSS 15.0 Row statistical procedures.

2. result and analysis：

2.1. two groups of case distributions

This center enters group case load totally 60, wherein A groups 30, B groups 30, and A groups complete 26, and B groups complete 27, have been total to Into 53 Eligibilities.

Demography baseline compares before 2.2 treatments

Sex between two groups before treatment（P=0.678）, the age（P=0.241）Comparing difference no statistical significance（P>0.05）, tool There is comparativity.

2.3 clinical symptoms total marks compare.

Before treatment and after treatment（90 days）, in control group clinical symptoms integration group with more there is significant difference in treatment group （Treatment group P=0.000, control group P=0.000）, and treat after average be less than treatment before, illustrate in this research, hormone and hormone Combined with Chinese Herbal compound mixture treatment IPF can improve the clinical symptoms of patient；Treatment group and control group 30 days after the treatment, 60 My god, 90 days respectively carry out symptom integral group between compare：During the course for the treatment of 30 days, no difference of science of statistics between two groups（P=0.330）, treat During journey 60 days, there is significant difference between two groups（p=0.000）, during the course for the treatment of 90 days, have significant difference between two groups（p= 0.000）,（Note：Two groups of baseline values no difference of science of statistics, P=0.727, during the course for the treatment of 60 days, 90 days, treatment group's symptom integral is equal Value is less than control group）, illustrate the increase with the course for the treatment of（>60 days）, hormons Chinese medicine compound prescription mixture is in terms of symptom improvement Effect is better than hormone.

2.4 Results of Blood-gas compare.

Before treatment and after treatment（90 days）, treatment group and control group PO₂、PCO₂More there is significant difference in group（Treatment Group P=0.000, control group P=0.000）, and before average is more than treatment after treating, illustrate in this research, in hormone and hormons Medicine compound mixture treatment IPF can improve the PO of patient₂、PCO₂；Treatment group and control group 30 days after the treatment, 60 days, 90 natural gift PO is not carried out₂Group between compare：During the course for the treatment of 30 days, no difference of science of statistics between two groups（P=0.511）, during the course for the treatment of 60 days, two groups Between have significant difference（p=0.000）, during the course for the treatment of 90 days, have significant difference between two groups（p=0.000）,（Note：Two groups of bases The horizontal no difference of science of statistics of line, P=0.238, during the course for the treatment of 60 days, 90 days, treatment group PO₂Average is more than control group）.Treatment group with Control group carries out PCO in 30 days after the treatment, 60 days, 90 days respectively₂Group between compare：During the course for the treatment of 30 days, without statistics between two groups Learn difference（P=0.852）, during the course for the treatment of 60 days, have significant difference between two groups（p=0.000）, during the course for the treatment of 90 days, between two groups There is significant difference（p=0.000）,（Note：Two groups of baseline values no difference of science of statistics, P=0.797, during the course for the treatment of 60 days, 90 days, control Treatment group PCO₂Average is less than control group）.Illustrate the increase with the course for the treatment of（>60 days）, hormons Chinese medicine compound prescription mixture is in PO₂、 PCO₂Effect in terms of improvement is better than hormone.Before treatment and after treatment（90 days）, treatment group and control group SO₂More equal nothing in group Significant difference（p>0.05）, illustrate in this research, hormone is with hormons Chinese medicine compound prescription mixture to IPF patient SO₂Index without Influence；Treatment group carries out SO in 30 days after the treatment, 60 days, 90 days respectively with control group₂Compare between the group of index：The course for the treatment of 30 days, At 60 days, 90 days, equal no difference of science of statistics between two groups（P>0.05）,（Note：Two groups of baseline values no difference of science of statistics, P> 0.05）, illustrate in this research, hormons Chinese medicine compound prescription mixture is in SO₂Effect in terms of improvement is suitable with hormone.

2.5 PFT results contrasts.

Before treatment and after treatment（90 days）, treatment group is compared with control group TLC, VC, FEV1/FVC group without statistics Difference（p>0.05）, illustrate in this research, hormone is with hormons Chinese medicine compound prescription mixture to IPF patient TLC, VC, FEV1/FVC Index is without influence；Treatment group carries out TLC, VC, FEV1/FVC index in 30 days after the treatment, 60 days, 90 days respectively with control group Compare between group：During the course for the treatment of 30 days, 60 days, 90 days, equal no difference of science of statistics between two groups（P>0.05）,（Note：Two groups of baseline values No difference of science of statistics, P>0.05）, illustrate in this research, hormons Chinese medicine compound prescription mixture improves in TLC, VC, FEV1/FVC The effect of aspect is suitable with hormone.

Before treatment and after treatment（90 days）, in control group DLCO, FEV1 group with more there is significant difference in treatment group （DLCO treatment groups P=0.001, control group P=0.000；FEV1 treatment groups P=0.000, control group P=0.000）, and after treatment Before value is more than treatment, illustrate in this research, hormone can improve patient's with hormons Chinese medicine compound prescription mixture treatment IPF DLCO、FEV1；Treatment group and control group compare for 30 days after the treatment, 60 days, 90 days between the group for carrying out DLCO, FEV1 index respectively Compared with：At 60 days, 90 days, equal no difference of science of statistics between two groups（P ＜ 0.05）,（Note：Two groups of baseline values no difference of science of statistics, P >0.05）, illustrate in this research, effect of the hormons herb mixture in terms of DLCO, FEV1 improvement is better than hormone, and may It is directly proportional to the course for the treatment of.

Gait test in 2.6 6 minutes.

Before treatment and after treatment（90 days）, in control group 6min walking distance groups with more there is significant difference in treatment group （Treatment group P=0.000, control group P=0.004）, and treat after average be more than treatment before, illustrate in this research, hormone and hormone Combined with Chinese Herbal compound mixture treatment IPF can improve the 6min walking distances of patient；Treatment group and control group 30 days after the treatment, Compare between the group for carrying out 6min walking distances respectively within 60 days, 90 days：During the course for the treatment of 30 days, no difference of science of statistics between two groups（P= 0.554）, during the course for the treatment of 60 days, have significant difference between two groups（p=0.000）, during the course for the treatment of 90 days, have statistics poor between two groups It is different（p=0.000）,（Note：Two groups of baseline values no difference of science of statistics, P=0.771, during the course for the treatment of 60 days, 90 days, treatment group 6min steps Row distance average is more than control group）, illustrate the increase with the course for the treatment of（>60 days）, hormons Chinese medicine compound prescription mixture is in 6min steps Effect in terms of row distance improvement is better than hormone.

2.7 inflammatory factors determine.

Before treatment and after treatment（90 days）, in control group TGF-β, IL-4, IL-13 group with more there is statistics in treatment group Learn difference（Treatment group P=0.000, control group P=0.000）, and treat after average be less than treatment before, illustrate in this research, hormone Group can improve TGF-β, IL-4, IL-13 of patient with hormons Chinese medicine compound prescription mixture treatment IPF；With treating before treatment Afterwards（90 days）, in control group IL-12, IFN-γ group with more there is significant difference in treatment group（Treatment group P=0.000, control Group P=0.000）, and before average is more than treatment after treating, illustrate in this research, the treatment of hormone and hormons Chinese medicine compound prescription mixture IPF can improve IL-12, the IFN-γ of patient；Treatment group is carried out for 30 days after the treatment, 60 days, 90 days respectively with control group TGF-β, IL-4, IL-13, IL-12, IFN-γ index group between compare：At 60 days, 90 days, without statistics between two groups Difference（P ＜ 0.05）,（Note：Two groups of baseline values no difference of science of statistics, P>0.05）, illustrate in this research, hormons Chinese medicine Compound mixture can adjust the expression of TGF-β, IL-4, IL-13, IL-12, IFN-γ, and it acts on and is better than hormone group, can Can be directly proportional to the course for the treatment of.

2.8 curative effect of disease results.

Test group total effective rate is 100%, and hormone group total effective rate is 85.19%, and two groups relatively have significant difference（P= 0.041）, illustrate that effect of the hormons Chinese medicine compound prescription mixture in terms of total effective rate improvement is better than hormone group.

Conclusion.

In this research, hormons Chinese medicine compound prescription mixture can improve the clinical symptoms of IPF patient with hormone, improve The blood gas analysis index such as PO2, PCO2, improve the lung function index such as DLCO, FEV1, improve 6min walking distances and improve IPF Serum tgf-beta, IL-4, IL-13, IL-12, IFN-γ equimolecular index, and improve patient clinical symptom, PO2, In terms of the crucial final result index such as PCO2, DLCO, FEV1, six minutes gait tests, inflammatory factors, hormons Chinese medicine compound prescription ginseng dragon Mixture effect is better than hormone, and has certain relation with treatment course.

Claims

1. a kind of Chinese medicine preparation for treating idiopathic pulmonary fibrosis paracmasis disease, it is characterised in that the Chinese medicine preparation is by such as The raw material composition of lower parts by weight：Astragalus root 130-140 parts, wide dragon 60-70 parts, radix glehniae 82-88 parts, Radix Angelicae Sinensis 60- 70 parts, Ligusticum wallichii 60-70 parts, prepared rhizome of rehmannia 60-70 parts, honey-fried licorice root 60-70 parts, reticulate millettia 60-70 parts, tuber of dwarf lilyturf 60-70 part, bulb of thunberg fritillary Female 60-70 parts.

2. the Chinese medicine preparation for the treatment of idiopathic pulmonary fibrosis paracmasis disease according to claim 1, it is characterised in that should Chinese medicine preparation is made up of the raw material of following parts by weight：132 parts of astragalus root, 66 parts of wide dragon, 88 parts of radix glehniae, Radix Angelicae Sinensis 66 parts, 66 parts of Ligusticum wallichii, 66 parts of prepared rhizome of rehmannia, 66 parts of honey-fried licorice root, 66 parts of reticulate millettia, 66 parts of the tuber of dwarf lilyturf, 66 parts of fritillaria thunbergii.

3. the Chinese medicine preparation for the treatment of idiopathic pulmonary fibrosis paracmasis disease according to claim 1, it is characterised in that should The monarch drug in a prescription of Chinese medicine preparation is astragalus root and the composition of wide dragon.

4. the Chinese medicine preparation for the treatment of idiopathic pulmonary fibrosis paracmasis disease according to claim 1, it is characterised in that institute The formulation for stating Chinese medicine preparation is mixture or granule.

5. a kind of preparation method of the Chinese medicine preparation for the treatment of idiopathic pulmonary fibrosis paracmasis disease as claimed in claim 1, Characterized in that, the preparation method comprises the following steps：

6. the Chinese medicine preparation for the treatment of idiopathic pulmonary fibrosis according to claim 1, it is characterised in that take 2 by formula My god, it is twice daily, early to take within 30 minutes before meals（50-75ml）, supper half an hour after takes（50-75ml）, by this before taking Medicine preparation heats；More than half an hour is separated with other Chinese patent drugs, Western medicine；During medication, forbid taking pungent, fish raw meat, stimulating food, life Cold, greasy, sour and astringent F＆B.

A kind of 7. quality testing side of the Chinese medicine preparation for the treatment of idiopathic pulmonary fibrosis paracmasis disease as claimed in claim 1 Method, it is characterised in that through high effective liquid chromatography for measuring, determine Astragaloside IV, the calycosin glucoside in astragalus root For its index composition, using Astragaloside IV, calycosin glucoside as this product assay composition, for controlling this Quality, astragalus root must not be less than 10mg in terms of Astragaloside IV, in terms of calycosin glucoside, must not be less than 4mg.

8. the Chinese medicine preparation described in a kind of claim 1 is with hormone combination as preparation treatment idiopathic pulmonary fibrosis paracmasis disease Application in medicine.