CN101062074A - Compound of sphaeria sinensis and panax notoginseng extract and the application thereof in the preventing and treating of pulmonary fibrosis - Google Patents
Compound of sphaeria sinensis and panax notoginseng extract and the application thereof in the preventing and treating of pulmonary fibrosis Download PDFInfo
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Abstract
The invention discloses a cordycepin extract and notoginseng extract and application in prevention and cure pulmonary fibrosis medicine preparation, which is characterized by the following: extracting and condensing from China clothing hairs pore zymocyte powder with water and alcohol; getting cordycepin extract; setting Cordyceps sinensis adenosine, cordycepic acid, and Cordyceps sinensis polysaccharide more than raw bacteria powder about 3-8 double; extracting cordycepin extract from cordycepin crude drug with alcohol; separating large aperture absorption resin; purifying; getting the cordycepin extract; setting the content of cordycepin saponin more than raw cordycepin crude drug for 7-10 double; allocating the cordycepin and cordycepin saponin with mass percent at 90-10% and 10-90%; preparing medicinal compound. This invention possesses very big utility value in clinic.
Description
Technical field:
The present invention relates to technical field of Chinese medicines.Be specifically related to the compositions of Cordyceps and Radix Notoginseng extract and prevent and treat application in the pulmonary fibrosis medicine in preparation.
Background technology:
Cordyceps is to refer in particular to a kind of ascomycetes that colonizes on bat genus (Hepialus) larva.So-called ' grass ' is exactly its Stroma; ' worm ' is exactly its sclerotium, and just its sclerotium coated outside one deck worm corpse cot.
Cordyceps mainly is grown in the mesophorbium, coryphile of Chinese Qinghai-Tibet height above sea level 3500-5000 rice.Belong to national second class protection species.Modern age, resource was closely exhausted owing to excessively excavate, and price is your mistake gold.Separate and the artificial culture Cordyceps fungus, become current scientific worker's vital task.People from Cordyceps, separated multiple fungus.As Chinese Paecilomyces varioti (Paecilomyces sinensis Chen, Xiao﹠amp; Shi), Cordyceps cephalo (Cephalosporiumsinensis C.T.Chen.), Mortierella (Mortierella sp) and China pilose spore (Hirsutella sinensisX.J.Liu, Y.L.Guo, Y.X.Yu ﹠amp; W.Zeng) etc., and produce its mycelium with industrial fermentation technology, be developed to multiple worm grass products such as ' JINSHUIBAO ', ' mind calming treasured ', ' zhiling capsules '.But people identify with dna fingerprinting in the recent period, find that DNA collection of illustrative plates and the natural cordyceps difference of above-mentioned Paecilomyces varioti, cephalo bacterium etc. is very big, should not be referred to as Cordyceps fungus.Have only the dna fingerprinting of China pilose spore and natural Cordyceps to match, likelihood is up to 96%.Thereby China pilose spore is considered to real Cordyceps fungus (fungus system 19 (1): 60-64,2000; Fungus system 22 (1): 161-176,2003).
Cordyceps is Chinese valuable ingredient of Chinese medicine, and its effective ingredient is Cordyceps adenosine (adenosine), cordycepic acid (cordycepicacid) and Cordyceps polysaccharide (polysaccharides).Major function is an invigorating the lung and the kidney, hemostasis and phlegm.(one one of Pharmacopoeia of People's Republic of China version in 2005, p.75).
Radix Notoginseng is that (the dry root and rhizome of Panax notoginseng (Burk.) F.H.Chen is Chinese distinctive rare Chinese medicine to panax araliaceae plant.The active component of Radix Notoginseng is saponin (saponins), it is except that containing ginsenosides such as all Rg1 of congener Radix Ginseng, Rb1 and Rd, other contains arasaponins (notoginsenosides) such as the distinctive R1 of Radix Notoginseng, R2, R3, R4, R6, R7, is described as ' king in the ginseng '.The medicinal function of Radix Notoginseng is the dissipating blood stasis hemostasis, subduing swelling and relieving pain.(one one of Pharmacopoeia of People's Republic of China version in 2005, p.10-11).
Pulmonary fibrosis (Pulmonaryfibrosis, PF) be that a large amount of fibroblasts are at the pneumonocyte external sediment, and with the destructive pulmonary disease of pneumonia and lung tissue structure, still there is not specific drug (Ward PA so far, HunninghakeGW:Lung inflammation and fibrosis.American Journal of Respiratory and Critical CareMedicine, 1998,157:123-129).Pulmonary fibrosis is called pulmonary fistula in middle medical circles, is with dyspnea with shortness of breath, and coughing and telling turbid foam is that the deficient property of pulmonary of main symptom takes a disease.Mainly show as the alveolar inflammation early stage, and the later stage is interstitial pulmonary fibrosis, causes lung failure (Beijing traditional Chinese medical science, 1996 the 5th phase .9-10 pages or leaves) at last.
2005, the field fine jade found that Gentiana and Radix Notoginseng total arasaponins prescription can suppress the fibrosis (CN1698725) of Chronic obstructive pulmonary disease, but this prescription is not used Cordyceps or its fungus.
2006, Shanghai Univ. of Traditional Chinese Medicine discloses " a kind of Chinese medicine preparation that can improve pulmonary fibrosis ", and (CN1788764), said preparation was made up of Semen Persicae, Radix Salviae Miltiorrhizae, Herb Gynostemmae Pentaphylli, fermented Cordyceps powder, Pollen Pini and Fructus Schisandrae Chinensis.The first Application Cordyceps mycelium is prevented the smelting pulmonary fibrosis.But this invents used " fermented Cordyceps powder ", does not indicate by which kind of fungi fermentation to form, and used Chinese medicine does not also have the Radix Notoginseng component;
In January, 2007, discoveries such as Cifu Biological Tehcnology Co., Ltd., Hangzhou: Cordyceps and latent pore fungi (containing its fermented product) have the pulmonary fibrosis of inhibition effect, and compound recipe is than folk prescription better (CN1899318).This patent is used the fermented product of the fermented product of China pilose spore as Cordyceps fungus first, but this fermented product only is its mycelium and culture fluid, non-extract.In addition, also there is not Radix Notoginseng extract in this compound recipe.
Summary of the invention:
The technical problem to be solved in the present invention is to use the extract of Cordyceps fungus (hirsutella sinensis fungal) and Radix Notoginseng, designs their compositions and the application in the control pulmonary fibrosis thereof.
The invention provides the compositions of Cordyceps fungus and Radix Notoginseng extract.Described compositions contains Cordyceps fungus extract that weight % proportioning is 90%-10% and the Radix Notoginseng extract of 10%-90%.
The raw material of described Cordyceps fungus is mycelium or the mycopowder (Jun Silk body and the mash of hirsutella sinensis fungal), they can obtain by Shen Ceng Pei Raising voluntarily, also can buy from city's field boundary.Requiring used strain must be China pilose spore, and its adenosine content is not less than 0.14%, and cordycepic acid is many 7.0%, and Cordyceps polysaccharide is no less than 1.0%
Chinese medicine extract (Extraction) is the product of the further separation and purification of Chinese medicine crude drug, and active component obtains highly concentrated, is the elite of Chinese medicine crude drug.The Cordyceps fungus extract that the present invention uses, its effective ingredient--Cordyceps adenosine, cordycepic acid and Cordyceps polysaccharide is than careless bacterium Silk body of worm summer in winter or the high 3-8 of mycopowder times; Content of the total saponins in radix notoginseng in the Radix Notoginseng extract improves 7-10 doubly than Radix Notoginseng crude drug.
Another object of the present invention has provided the preparation method of Cordyceps fungus and Radix Notoginseng extract, and this method comprises the following steps:
(1) preparation of Cordyceps fungus extract
(1) gets sutella sinensis fermented mycelium or mycopowder and add the water that mycelium or mycopowder juice 8-10 doubly measure (w/v), stir down at 90-98 ℃ and extracted 1-3 hour;
(2) get aqueous extract 1. after the filtration; Residue is doubly measured in addition the water of (w/v) with 5-8, stir down at 90-98 ℃ and extracted 1-2 hour, filter aqueous extract 2., reuse 5-8 doubly measures the water of (w/v), stirs down at 90-98 ℃ and extracts 1-2 hour, filter aqueous extract 3.;
(3) merge aqueous extract 1., 2., 3., be evaporated to the concentrated solution that specific density reaches 1.04-1.09;
(4) residue of water intaking after carrying adds 95% ethanol that 3-5 doubly measures (w/v), reflux extraction 1-3 hour, after the filtration alcohol extract 4., residue adds 95% ethanol that 3-5 doubly measures (w/v) again, reflux extraction 2 times, filter alcohol extract 5., 6.;
(5) merge alcohol extract 4., 5., 6., get fluid extract through concentrating under reduced pressure;
(6) above-mentioned water extracting liquid and alcohol extraction fluid extract is evenly mixed, mixing liquid is spray-dried, lyophilization or vacuum drying get the Cordyceps fungus extract;
The also available hirsutella sinensis fungal mycelium of Cordyceps fungus extract is a raw material, gets through 30-70% alcohol reflux 3 times.Solvent load: for the first time be with mycelium or mycopowder juice 8-10 doubly, doubly measure w/v for 5-8 the 2nd, 3 time, extraction time respectively is 1-3 Xiao Time, and is concentrated the same with drying means;
Require that Cordyceps adenosine content (in adenosine) in this product is not less than 0.5%, cordycepic acid (in mannitol) is not less than 20%, Cordyceps polysaccharide (in Portugal's glucose) is not less than 5%, be Cordyceps adenosine, cordycepin and the Cordyceps polysaccharide content in the extract, doubly than the high 3-8 of corresponding composition in the former mycopowder.(Fig. 1, table 1)
(2) preparation of Radix Notoginseng extract:
(1) alcohol extraction: get the coarse powder of Radix Notoginseng crude drug (root), doubly measured (w/v) 50-75% alcohol reflux 2-3 hour in order to Radix Notoginseng coarse powder juice 8-12, filter alcohol extract; Residue reuse 8-10 doubly measures (w/v) 50-75% ethanol and repeats to extract 2 times, 3 alcohol extracts are evaporated to dried, the Radix Notoginseng ethanol extract;
(2) absorption: make adsorbent with nonpolar macroporous adsorbent resin; Earlier above-mentioned Radix Notoginseng ethanol extract is dissolved in water, is made into every milliliter of solution that is equivalent to contain crude drug 0.3-0.5g, the chromatographic column of flowing through then is adsorbed on the HPD-100 macroporous adsorbent resin arasaponin;
(3) desorption: first water elution chromatography post, to remove impurity such as sugar.And then use the 50-70% ethanol elution; Arasaponin desorption from the adsorption column is got off.Merge the alcohol eluen that contains saponin,
(4) decolouring: (3) alcohol eluen of obtaining set by step, add 1% active carbon (w/v), Stir mixes decolouring 30 minutes,
(5) drying: (4) destaining solution of obtaining set by step, get filtrate after filtering.Filtrate gets this product through concentrating under reduced pressure, vacuum drying.
Radix Notoginseng extract also can extract from the Radix Notoginseng rhizome, and method is the same.Require the total saponin content in the Radix Notoginseng extract to be not less than 70%, doubly than the high 7-10 of saponin content in the former Radix Notoginseng crude drug.(table 1)
Active component content compares * in table 1. Cordyceps fungus and Radix Notoginseng crude drug and the extract thereof
| Project | Cordyceps adenosine (mg/g) | Cordycepic acid (%) | Cordyceps polysaccharide (%) | Radix Notoginseng total arasaponins (%) |
| Cordyceps fungus mycopowder Cordyceps fungus powder extracts Radix Notoginseng Radix Notoginseng extract | 0.19 0.92 -- -- | 7.3 34.2 -- -- | 1.6 9.0 -- -- | -- -- 7.8 75.1 |
* P.300-301, measure by " mensuration of adenosine in the health food " method by Ministry of Health of the People's Republic of China's " health food check and assessment technique standard (version in 2003) " for the Cordyceps adenosine content;
The content of cordycepic acid, " the HPLC method is measured the mannitol in the Cordyceps " method of pressing Dong Chunming measure (the Gansu chemical industry, 2005 the 3rd phases, p.45-48)
The content of Cordyceps polysaccharide is with reference to one one of Pharmacopoeia of People's Republic of China version in 2005, and p.130, the method for ganoderan is measured;
P.306-307, measure by " mensuration of total saponins in the health food " method by Ministry of Health of the People's Republic of China's " health food check and assessment technique standard (version in 2003) " for Radix Notoginseng total arasaponins;
The compositions of Cordyceps fungus of the present invention and Radix Notoginseng extract can be made pharmaceutical compositions such as oral granular formulation, tablet, capsule or oral liquid according to a conventional method with pharmaceutic adjuvant.
Another object of the present invention has provided Cordyceps fungus and Radix Notoginseng extract and has prevented and treated application in the pulmonary fibrosis medicine in preparation.
The present invention is by the effect of following experimental observation treatment pulmonary fibrosis.
The inventor adopts that classical (bleomycin, BLM) the Mus pulmonary fibrosis animal model of sensitization, test Cordyceps fungus and Radix Notoginseng extract be to the therapeutic effect of pulmonary fibrosis, and make comparisons with hormone (prednisolone acetate) treatment group by bleomycin.
Bleomycin is injected by trachea, consumption: 5mg/Kg immediately with the mice rotation, makes BLM uniform distribution in the Mus lung after the injection.Next day after mice is injected bleomycin, give extract of the present invention or hormone therapy, dosage is respectively 0.15-0.6g/Kg or 6.67mg/Kg.
Each organizes mice when raising the 7th, 14 and 28 day, cuts open breast and gets lung.Right lung is surveyed the content (lung collagenzation level index) of hydroxyproline after homogenate; Left side lung is done the pathology section, and usefulness Saepiel SV et al method (Am Rev RespirDis, 1979,120:893-899), alveolitis and pulmonary fibrosis degree of each group mice are made scoring, and grade scoring is converted into continuous data with SPSS11.5 software.
The result: smelting treatment group of the present invention is compared with model group, the difference highly significant, and its alveolitis degree has only half of model group, and the pulmonary fibrosis degree is less than 1/3rd of model group.In the time of the 28th day, the hydroxyproline content of smelting treatment group of the present invention also is starkly lower than hormone smelting treatment group, with suitable (table 2,3,4) of normal group.
Table 2 Cordyceps fungus and Radix Notoginseng extract are to the therapeutic effect of bleomycin sensitized mice alveolitis
☆(x ± s, n=8)
| The Szaopiel score value | The P value | |
| Normal group | 0.38±0.52 |
| Model group steroid group treatment group embodiment 1 embodiment of the |
2.38±0.52## 1.25±0.46** 0.88±0.35** 1.13±0.35** 1.25±0.46** | ## and normal group are than P＜0.01; * and model group ratio, P＜0.01 |
After the ☆ bleomycin sensitization the 7th day
Table 3 Cordyceps fungus and Radix Notoginseng extract are to the influence of bleomycin sensitized mice pulmonary fibrosis degree
☆(x ± s, n=8)
| Dosage | The Szaopiel score value | The P value |
| Normal group model group steroid group treatment group embodiment 1 embodiment of the | 0.25±0.46 1.75±0.71## 0.50±0.54 0.38±0.54** 0.50±0.76** 0.50±0.76** | ## and normal group are than P＜0.01; * and model group ratio, P＜0.01 |
After the ☆ bleomycin sensitization the 14th day
Table 4 Cordyceps fungus and Radix Notoginseng extract are to the influence of hydroxyproline content in the bleomycin sensitized mice lung tissue
☆(ug/mg, x ± s, n=8)
| Group | Hydroxyproline content (μ g/mg) | The P value |
| Normal group model group steroid group treatment group embodiment 1 embodiment of the | 0.63±0.09 0.88±0.03## 0.86±0.06 0.65±0.09** 0.66±0.10** 0.68±0.04** | ## and normal group are than P＜0.01; * and model group ratio, P＜0.01 |
After the ☆ bleomycin sensitization the 28th day
The present invention becomes Chinese medicine compound with Cordyceps with the Radix Notoginseng extract compatibility, and every side takes its active component again and obtains highly spissated extract, and therefore, its effect that suppresses pulmonary fibrosis is fairly obvious.
Cordyceps fungus and Radix Notoginseng extract can be made into the medicine of control pulmonary fibrosis.
Description of drawings:
The HPLC chromatogram of Fig. 1 Cordyceps fungus and extract thereof.
*The HPLC instrument: Beckman System Gold type, 125 HPLC pumps, 168 photodiode array UV-detector, post: Hypersil BDS-C18 (4.6mm*250mm, 5um), mobile phase: methanol: 0.01mol/LKH
2PO
4=9: 91, the column oven temperature: 25 ℃, flow: 1ml/min.Detect wavelength: 254nm, function software: Beckman 32Karat.
Diagram: the red lines of last figure are the absorption curve of Cordyceps fungus mycopowder extract; Black lines is the absorption curve of Cordyceps fungus mycopowder; The RT value of Cordyceps adenosine is 15 ', and the absworption peak area of the former Cordyceps adenosine is 7714155, and the latter is 1612200, and the former is bigger 4.8 times than the latter.
Fig. 2-5 Cordyceps and Radix Notoginseng extract treatment pulmonary fibrosis mouse lung tissue pathological slice figure (treated 28 days; HE * 40).
Fig. 2 normal control group: lung tissue structure is clear, and alveolar wall is not seen and thickened, the alveolar epithelial cells structural integrity, and alveolar space is bright.Do not see that inflammatory cell is invaded profit and interstitial collagen deposits;
Fig. 3 bleomycin model group: the proliferation of fibrous tissue kitchen range that See differs in size, the obvious broadening of alveolar septum, alveolar structure destroys serious, and the part alveolar space disappears;
Fig. 4 steroid group: with the model group ratio, alveolar structure is complete substantially, the broadening of part alveolar septum, a small amount of collagen deposition of peripheral See;
Fig. 5 Cordyceps and Radix Notoginseng extract treatment group: alveolar structure is complete, and alveolar space is bright, and fibroblast has hypertrophy and collagen deposition amount few, with the model group ratio, pulmonary fibrosis obviously improves.
The specific embodiment:
Cordyceps provided by the invention and Radix Notoginseng extract compositions have obvious suppression mouse pulmonary fibrosis effect, can be used to prepare the pharmaceutical composition that control suppresses pulmonary fibrosis, and bigger using value is arranged clinically.
The preparation of embodiment 1. Cordyceps fungus extracts
One, send out the ferment bacterium Silk body from China pilose spore and to extract
(1). get China pilose spore and send out ferment bacterium Silk body 10Kg, add deionized water 100Kg, extracted 2 hours down 95 ℃ (± 3).Use 50 μ membrane filtrations while hot, get aqueous extract 1; Residue extracts 2 times down 95 ℃ (± 3) with the 60Kg deionized water in addition, each 1 hour, gets aqueous extract 2,3 after the filtration;
(2). merge aqueous extract 1,2 and 3, be evaporated to specific density and reach 1.04, get the water extraction concentrated solution of Cordyceps fungus;
(3). above-mentioned water is carried the back residue add 95% ethanol 50Kg, under 80 ℃ (± 1 ℃), reflux extraction 3 hours, use 50 μ membrane filtrations while hot, get alcohol extract 1, residue adds 95% ethanol 25Kg again, reflux extraction is 2 times under 80 ℃ (± 1 ℃), each 1 hour, gets alcohol extract 2,3 after the filtration;
(4). merge alcohol extract 1,2,3, concentrating under reduced pressure gets fluid extract;
(5). above-mentioned water extraction concentrated solution and fluid extract is mixed, be lower than 5% 60 ℃ of following vacuum drying to water content;
(6) be the Cordyceps fungus extract after the pulverizing.
This product contains Cordyceps adenosine 0.95%, cordycepic acid 34.18% through with HPLC and spectrophotometric analysis, Cordyceps polysaccharide 8.98%, and the Cordyceps adenosine of former mycopowder is 0.19%, cordycepic acid 7.36%, Cordyceps polysaccharide 1.60%, extract improves 4.8,4.6 and 5.6 times respectively than former mycopowder.(table 1)
Two, from China pilose spore mycopowder (mash dry powder), extract
Get hirsutella sinensis fungal powder 10Kg, add 100Kg50% alcohol reflux 3 Xiao Time, filter extract 1, it is twice of 40% alcohol reflux that residue adds 50Kg concentration again, each 1.5 Xiao Time, filter extract 2 and 3, united extraction thing 1,2 and 3, being evaporated to specific density is that drying is revealed in 1.04 back sprays, promptly.Through with HPLC and spectrophotometry, its Cordyceps adenosine content is 0.64%, and cordycepic acid content is 25.17%, Cordyceps polysaccharide content is 5.82%.
The preparation of example 2. Radix Notoginseng extracts
One, from Radix Notoginseng, extracts
(1). get Radix Notoginseng crude drug (root) 10Kg, 8 mesh sieves are crossed in section, pulverizing;
(2) add 70% ethanol of 10 times of amounts, reflux, extract, 2 hours, after the filtration alcohol extract 1;
(3) 70% alcohol reflux of 8 times of amounts of residue reuse is 2 times, each 1 hour, gets alcohol extract 2,3 after the filtration;
(4). merge alcohol extract 1,2 and 3, concentrating under reduced pressure gets fluid extract;
(5). in fluid extract, add the deionized water dissolving, make solution concentration reach every milliliter and be equivalent to contain crude drug 0.4 gram;
(6). above-mentioned solution is splined on macroporous adsorbent resin (HPD-100 type) chromatographic column, makes saponin be adsorbed on the resin resin demand: 4Kg, applied sample amount: be about 1.5 times of column volume;
(7). eluting elder generation water, approximately need be with the water of 2 column volumes, with eccysis impurity; To be adsorbed on 50% ethanol then that saponin washes elution speed on the resin: per minute 0.6-0.9ml.With the thin layer chromatography monitoring, collect the eluent that contains arasaponin simultaneously;
(8). merge the eluent that contains arasaponin, add 100g active carbon reflux decolour 30 minutes;
(9). decompress filter gets filtrate.Concentrating filter liquor, fluid extract promptly gets this product behind the vacuum drying.
This product HPLC method is measured, and contains Radix Notoginseng total arasaponins 75.1%, than high 9.6 times (table 1) of Radix Notoginseng crude drug
Two, from Radix Notoginseng
The middle extraction:
(1). get Radix Notoginseng rhizome 10Kg, 12 mesh sieves are crossed in section, pulverizing;
(2) add 70% ethanol of 10 times of amounts, reflux, extract, 2 hours, after the filtration alcohol extract 1;
(3) 70% alcohol reflux of 8 times of amounts of residue reuse is 2 times, each 1 hour, gets alcohol extract 2,3 after the filtration;
(4). merge alcohol extract 1,2 and 3, be evaporated to and be fluid extract;
(5). in fluid extract, add the deionized water dissolving, make solution concentration reach every milliliter and be equivalent to contain crude drug 0.35 gram;
(6). with above-mentioned solution application of sample on D-101 macroporous adsorption resin chromatography post,
(7). the amount of 3 column volumes of first water eluting, wash with the saponin that 50% ethanol will be adsorbed on the resin then,
(8). merge the eluent that contains arasaponin, add 1% (w/v) active carbon, reflux decolour 30 minutes;
(9). filter, concentrating filter liquor is thick fluid extract, vacuum drying, promptly.
This product is analyzed through the HPLC method, contains Radix Notoginseng total arasaponins 74.3%.
Example 3. pulmonary fibrosis resistants are measured
With above-mentioned Cordyceps fungus extract and the Radix Notoginseng extract that makes, mixed mutually in 7: 3 ratios, make therapeutic dose with the dosage of 0.6g/Kg then, irritate stomach in pulmonary fibrosis mice with bleomycin sensitization.After administration the 7th, 14 and 28 day, comparative observation was respectively organized the alveolitis of pathological section and the hydroxyproline content in pulmonary fibrosis degree and the lung tissue, and compares with normal mouse, bleomycin model group and steroid group.
The result: in the section of the 7th day lung pathology of model group, alveolar space has been seen has a large amount of macrophages, neutrophilic granulocyte and plasma cell to ooze out, and alveolitis is obvious; In the 14th day lung pathology section, alveolar septum is broadening, a large amount of hypertrophy of fibroblast and collagen stroma; In the 28th day lung pathology section, the destroyed of part alveolar structure, the alveolar space atrophy, alveolar septum significantly thickens and forms the fibrosis cicatrix.And in the pathological section of treatment group of the present invention, no matter early stage alveolitis (the 7th day), or the pulmonary fibrosis of intermediary and later stages and collagenzation degree (the 14th and 28 day) all are starkly lower than model group.As the 7th day alveolitis Saepiel score value of model group is 2.38, and smelting treatment group of the present invention only is 0.88 (P＜0.01), alleviates than model group that half is many; The 14th day lung tissue fibrosis and for example, the Saepiel score value of model group is 1.75, treatment group of the present invention only is 0.38 (P＜0.01), alleviates 3/4 than model group; The 28th day lung tissue hydroxyproline content for another example, model group is 0.88 μ g/mg, smelting treatment group of the present invention only is 0.68 μ g/mg (P＜0.01), and is suitable with normal control group (0.63 μ g/mg).See Table 2,3,4 and figure I.
Example 4
It is described to press embodiment one, make Cordyceps fungus extract and Radix Notoginseng extract respectively, and it is mixed mutually in 8: 2 ratio, make therapeutic dose with the dosage of 0.3g/Kg then, irritate stomach in the pulmonary fibrosis mice of using bleomycin sensitization, after administration the 7th, 14 and 28 day, comparative observation was respectively organized the hydroxyproline content in alveolitis, pulmonary fibrosis degree and the lung tissue of pathological section, and compared with normal mouse, bleomycin model group and steroid group.The result: the alveolitis Saepiel score value of treatment group of the present invention is 1.13, and the Saepiel score value of pulmonary fibrosis degree is 0.50, and the lung tissue hydroxyproline content is 0.66 μ g/mg, and three indexs and model group ratio all are remarkable difference (P＜0.01=.See Table 2,3,4.
Example 5
Press the extracting method that embodiment one introduces, be prepared into Cordyceps fungus extract and Radix Notoginseng extract respectively.Mixed mutually in 9: 1 ratio then, dosage with 0.15g/Kg is made therapeutic dose, irritate stomach in the pulmonary fibrosis mice of using bleomycin sensitization, respectively organize the alveolitis, pulmonary fibrosis degree of the 7th, 14 day pathological section and the 28th day lung tissue hydroxyproline content, and compare with normal mouse, bleomycin model group and steroid group.The result: treat pulmonary fibrosis with the present embodiment prescription, similar to embodiment one, two, all can obviously alleviate pulmonary fibrosis degree by bleomycin sensitization, i.e. its alveolitis, interstitial pulmonary fibrosis and collagenzation degree, all be improved significantly.See Table 2,3,4.
Claims (5)
1, the compositions of a kind of Cordyceps fungus and Radix Notoginseng extract is characterized in that it is 90%～10% Cordyceps fungus extract and 10%～90% Radix Notoginseng extract that described compositions contains weight proportion %.
2, according to the compositions of described Cordyceps of claim 1 and Radix Notoginseng extract, the raw material that it is characterized in that wherein said Cordyceps fungus is Hirsutella sinensis De Jun Silk body or mycopowder.
3, a kind of preparation of compositions method as Cordyceps fungus and Radix Notoginseng extract is characterized in that described preparation method comprises the following steps:
(1) preparation of Cordyceps fungus extract
(1) gets Hirsutella sinensis Fa Jiao Jun Silk body or mycopowder, add the water that mycelium or mycopowder meter 8-10 doubly measure w/v, stir down at 90-98 ℃ and extracted 1-3 hour;
Or with Hirsutella sinensis Jun Silk body or mycopowder, directly get solvent load with 30-70% alcohol reflux 3 times: for the first time for doubly to measure w/v with mycelium or mycopowder juice 8-10, the 2nd, 3 time is doubly amount amount w/v of 5-8, and extraction time respectively is 1-3 Xiao Time;
(2) get aqueous extract 1. after the filtration; Residue is doubly measured in addition the water of w/v with 5-8, stir down at 90-98 ℃ and extracted 1-2 hour, filter aqueous extract 2., reuse 5-8 doubly measures the water of w/v, stirs down at 90-98 ℃ and extracts 1-2 hour, filter aqueous extract 3.;
(3) 1., 2., 3. step (2) aqueous extract is merged, or step (1) is directly used the alcohol reflux liquid of 30-70% alcohol reflux 3 times, be evaporated to the concentrated solution that specific density reaches 1.04-1.09;
(4) residue of water intaking after carrying adds 95% ethanol that 3-5 doubly measures w/v, reflux extraction 1-3 hour, after the filtration alcohol extract 4., residue adds the 95% alcohol reflux extraction 2 times that 3-5 doubly measures w/v again, filter alcohol extract 5., 6.;
(5) merge alcohol extract 4., 5., 6., get fluid extract through concentrating under reduced pressure;
(6) above-mentioned water extracting liquid and fluid extract is evenly mixed, spray-dried or lyophilization or vacuum drying get the Cordyceps fungus extract; Cordyceps adenosine content in the Cordyceps fungus extract in adenosine be not less than 0.5%, cordycepic acid content is not less than 20% in mannitol, Cordyceps polysaccharide content is not less than 5% in Portugal's glucose.
(2) preparation of Radix Notoginseng extract:
(1) alcohol extraction: get Radix Notoginseng crude drug coarse powder, doubly measure 50-75% alcohol reflux 2-3 hour of w/v with 8-12, filter alcohol extract; Residue reuse 8-10 amount w/v70-75% ethanol repeats to extract 2 times, each 1-2 Xiao Time, 3 alcohol extracts are evaporated to dried, the Radix Notoginseng ethanol extract;
(2) absorption: make adsorbent with nonpolar macroporous adsorbent resin, model is HPD-100, D-101 or AB-8; Earlier above-mentioned Radix Notoginseng ethanol extract is dissolved in water, is made into every milliliter of solution that is equivalent to contain crude drug 0.3-0.5g, the chromatographic column of flowing through then is adsorbed on the macroporous adsorbent resin arasaponin;
(3) desorption: first water elution chromatography post, to remove impurity such as sugar.And then use the 50-70% ethanol elution; Arasaponin desorption from the adsorption column is got off;
(4) decolouring: merge the alcohol eluen that contains saponin, add 1% active carbon Stir and mix decolouring 30 minutes;
(5) drying: filter destaining solution, destaining solution behind concentrating under reduced pressure, vacuum drying gets this product, the content of its Radix Notoginseng total arasaponins is not less than 70%.
4, the compositions of described Cordyceps fungus of a kind of claim 1 and Radix Notoginseng extract is prevented and treated application in the pulmonary fibrosis medicine in preparation.
5, the compositions of Cordyceps fungus according to claim 4 and Radix Notoginseng extract is prevented and treated application in the pulmonary fibrosis medicine in preparation, it is characterized in that described medicine is oral granular formulation, tablet, capsule or oral liquid.
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Effective date of registration: 20071012 Address after: Room 9, building 500, No. 9110, Shanghai, Caobao Road Applicant after: Shanghai Zhicao Bio-Tech Co., Ltd. Co-applicant after: Suzhou Inst. of Chinese Medicine Address before: Room 9, building 500, No. 9110, Shanghai, Caobao Road Applicant before: Shanghai Zhicao Bio-Tech Co., Ltd. |
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Application publication date: 20071031 |