CN101543574B - Chinese medicinal composition for treating pulmonary interstitial fibrosis - Google Patents
Chinese medicinal composition for treating pulmonary interstitial fibrosis Download PDFInfo
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Abstract
The invention relates to a Chinese medicinal composition for treating pulmonary interstitial fibrosis, which comprises the following Chinese medicinal components by weight portion: 1 portion of unibract fritillary bulb, 0.1 to 1.0 portion of Paecilomyces bepiali chen, 1.5 to 4 portions of pseudo-ginseng, 1 to 3 portions of Rhodiola rosea L., 1 to 5 portions of Breviscapinun, 1 to 5 portions of red sage root, 1 to 3 portions of ginkgo leaf, 0.1 to 0.6 portion of sanguisuga, 0.1 to 0.6 portion of earthworm and 1 to 5 portions of Common Anemarrhena Rhizome; and the Chinese medicinal components are raw powder of the Chinese medicinal materials or Chinese medicinal extracts equal to crude drug dosages of the Chinese medicinal materials. The Chinese medicinal composition can be used for treating diseases such as pulmonary interstitial fibrosis and the like.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition, specifically, is a kind of Chinese medicine composition that is used for the treatment of diseases such as interstitial pulmonary fibrosis, and the component of said composition can be directly to be ground into Chinese crude drug that powder is used as medicine and/or the Chinese medicine extract that obtains through extraction.
Background technology
Idiopathic pulmonary interstitial fibrosis (be called for short IPF, pulmonary fibrosis) is with carrying out property dyspnea, pant, breathe hard, dry cough, breathe heavily that to suppress be clinical manifestation, be the interstitial lung disease of characteristics with restrictive ventilatory functional disturbance, hypoxemia, chronic progressive external diffuse interstitial pulmonary fibrosis.Be alveolitis in early days, finally cause the irreversibility fibrosis.Idiopathic pulmonary interstitial fibrosis pathogenesis complexity, complicated inflammatory paathogenic factor causes immunoregulatory disorder, oxygen free radical injury, collagenic supersession is unbalance, causes alveolar substrate to be rebuild and forms interstitial pulmonary fibrosis.Along with the variation of environment for human survival, its M ﹠ M increases day by day.Idiopathic pulmonary interstitial fibrosis prognosis extreme difference and lack effective Therapeutic Method so far, modern western medicine is based on hormone, immunosuppressant and interferon, curative effect is relatively poor, mean survival time (MST), only have 5 years, lose early treatment chance person, even chronic type its mean survival time (MST) also only is 3.2 years, it is refractory disease that WHO classifies it as lung, classifies one of first-selected disease of lung transplantation as.
At present along with development of molecular biology, has carried out cytokine network complicated in the inflammation of mediation pulmonary fibrosis and the fibrosis substrate reconstruction after this and their Its Mechanisms the world, research is thought cytokine to the significant effects effect that is formed with of interstitial pulmonary fibrosis, and then begins to seek to use relaxin, antioxidation preparation, cytokine antagonist treatment pulmonary fibrosis.And China's level of economic development is lower, even effectively the cytokine therapy pulmonary fibrosis also can't be received treatment because of its vast patient that costs an arm and a leg.Have the foreign scholar to study and attempt to treat pulmonary fibrosis with lung transplantation, cast aside the economic cost problem, lung organ transplantation success rate is lower, can not solve this difficult problem of interstitial pulmonary fibrosis.This shows that Chinese patent medicine is still very weak comparatively speaking in the treatment market of interstitial pulmonary fibrosis, thus market in urgent need develop a kind of determined curative effect and significantly, the Chinese medicine medicine of sophisticated technologies, diseases such as treatment interstitial pulmonary fibrosis that drug quality is stable.
Summary of the invention
The present invention be at the clinical practice Chinese medicine 100 many cases interstitial pulmonary fibrosis patients, clinical observation confirms that Chinese herb decoction treatment interstitial pulmonary fibrosis has significantly curative effect, can obviously improve symptom, improves patient's life quality.On the basis of a large amount of clinical case treatments, the pathogenesis etiology and the pathogenesis of interstitial pulmonary fibrosis have been furtherd investigate, think that the blood stasis damp-phlegm is the pathological changes basis of impatency in the lung network, diseases caused by exogenous pathogenic factor repeatedly on the internal injury basis increase the weight of PD, the deficiency of vital energy deficiency of YIN is that the turbid numbness resistance of stasis of blood lung network makes due to the body anoxia, with promoting blood circulation to remove obstruction in the collateral, QI invigorating reason lung ruling by law treatment interstitial pulmonary fibrosis patient effect is preferably arranged.Previously carried out the experimentation of Chinese medicine and hormone contrast treatment IPF, the anti-interstitial pulmonary fibrosis rat model of Chinese medicine, observing demonstration Chinese medicine has anti-preferably interstitial pulmonary fibrosis effect than the hormone group.
The present invention is effective Chinese medicine compound of the treatment interstitial pulmonary fibrosis that goes out through the clinical treatment research summary, be through extracting the pure Chinese medicinal preparation that makes by Chinese medicines such as Bulbus Fritillariae Cirrhosae, Cordyceps mycelium, Radix Notoginseng, Radix Rhodiolae, Hirudo, Folium Ginkgo, Radix Salviae Miltiorrhizae, Herba Erigerontis, Pheretima, the Rhizoma Anemarrhenaes, have improving inspiration by invigorating kidney-QI astringe the lung relieving asthma, the effect of promoting blood circulation to remove obstruction in the collateral eliminating stagnation, and determined curative effect, safe and effective.
The medicine that the object of the invention is to provide a kind of Chinese medicine composition and comprises said composition, this medicine can be treated diseases such as interstitial pulmonary fibrosis.
The object of the invention also is to provide the preparation method of above-mentioned composition and medicine, by this method, can obtain being used for the treatment of evident in efficacy, the sophisticated technologies of interstitial pulmonary fibrosis, stay-in-grade pharmaceutical composition.
The object of the invention also is to provide above-mentioned composition to be used for the treatment of the purposes of diseases such as interstitial pulmonary fibrosis.
In order to achieve the above object, the invention provides a kind of Chinese medicine composition, said composition comprises following parts by weight of Chinese traditional medicine component: 1 part of Bulbus Fritillariae Cirrhosae, Cordyceps mycelium 0.1-1.0 part, Radix Notoginseng 1.5-4 part, Radix Rhodiolae 1-3 part, Herba Erigerontis 1-5 part, Radix Salviae Miltiorrhizae 1-5 part, Folium Ginkgo 1-3 part, Hirudo 0.1-0.6 part, Pheretima 0.1-0.6 part, Rhizoma Anemarrhenae 1-5 part, described Chinese medicinal components is above-mentioned Chinese crude drug fecula or be equivalent to the Chinese medicine extract of above-mentioned Chinese crude drug crude drug amount.
In a preferred embodiment of the invention, above-mentioned Chinese medicine composition is made up of following parts by weight of Chinese traditional medicine component: 1 part of Bulbus Fritillariae Cirrhosae, 0.3 part of Cordyceps mycelium, 2.5 parts of Radix Notoginseng, 1.7 parts of Radix Rhodiolaes, 2.5 parts of Herba Erigerontiss, 2.5 parts of Radix Salviae Miltiorrhizaes, 1.7 parts of Folium Ginkgos, 0.3 part of Hirudo, 0.3 part of Pheretima, 1 part of the Rhizoma Anemarrhenae, described Chinese medicinal components can be above-mentioned Chinese crude drug fecula or the Chinese medicine extract that is equivalent to the crude drug amount of above-mentioned Chinese crude drug.
Wherein, the above-mentioned Rhizoma Anemarrhenae is the stir-baked RHIZOMA ANEMARRHENAE before sprinking salt solution of concocting; This concocting method is approach well known.
And above-mentioned Chinese medicinal components comprises Bulbus Fritillariae Cirrhosae, Radix Rhodiolae, Radix Notoginseng, Herba Erigerontis, Folium Ginkgo, Radix Salviae Miltiorrhizae, the Rhizoma Anemarrhenae, and it is the aqueous extract of this Chinese crude drug; Cordyceps mycelium, Pheretima and Hirudo are former powder.
In another preferred embodiment of the present invention, above-mentioned Chinese medicine composition is made up of following parts by weight of Chinese traditional medicine component: 1 part of Bulbus Fritillariae Cirrhosae, Cordyceps mycelium 0.2-0.5 part, Radix Notoginseng 2-4 part, Radix Rhodiolae 1-2 part, Herba Erigerontis 2-4 part, Radix Salviae Miltiorrhizae 2-4 part, Folium Ginkgo 1-3 part, Hirudo 0.2-0.5 part, Pheretima 0.2-0.5 part, Rhizoma Anemarrhenae 1-3 part, described Chinese medicinal components are the Chinese medicine extract that is equivalent to the crude drug amount of above-mentioned Chinese crude drug.
In another preferred embodiment of the present invention, above-mentioned Chinese medicine composition is made up of following parts by weight of Chinese traditional medicine component: 1 part of Bulbus Fritillariae Cirrhosae, Radix Rhodiolae 1.5-1.8 part, Radix Notoginseng 2.2-3 part, Herba Erigerontis 2.2-3.0 part, Folium Ginkgo 1.5-1.8 part, (stir-fry) Radix Salviae Miltiorrhizae 2.2-3.0 part, Cordyceps mycelium 0.2-0.4 part, Hirudo 0.2-0.4 part, Pheretima 0.2-0.4 part, Rhizoma Anemarrhenae 1-2 part.
The present invention also provides a kind of medicine for the treatment of interstitial pulmonary fibrosis, comprising above-mentioned Chinese medicine composition and pharmacy acceptable auxiliary.
Medicine provided by the invention, its component comprises: 1 part of Bulbus Fritillariae Cirrhosae, Cordyceps mycelium 0.1-1.0 part, Radix Notoginseng 1.5-4 part, Radix Rhodiolae 1-3 part, Herba Erigerontis 1-5 part, Radix Salviae Miltiorrhizae 1-5 part, Folium Ginkgo 1-3 part, Hirudo 0.1-0.6 part, Pheretima 0.1-0.6 part, Rhizoma Anemarrhenae 1-3 part, and pharmacy acceptable auxiliary; Above-mentioned Chinese medicinal components is the Chinese medicine extract that is equivalent to the crude drug amount of above-mentioned Chinese crude drug.
The medicine of above-mentioned treatment interstitial pulmonary fibrosis is preferably peroral dosage form, comprises dosage forms such as honeyed pill, condensed water honeyed pill, the watered pill, granule, capsule, tablet, powder, unguentum, oral liquid or syrup; This medicine is granule, capsule, tablet or powder more preferably.
Through overtesting, the pharmacy acceptable auxiliary that screening obtains is preferably arbitrary or its combination in microcrystalline Cellulose, starch, the dextrin, and more preferably microcrystalline Cellulose, starch or dextrin most preferably are dextrin; The weight of this pharmacy acceptable auxiliary accounts for the 0.1-50% of this drug weight.
Compositions of the present invention and medicine are made up of Radix Rhodiolae, Radix Notoginseng, Herba Erigerontis, Folium Ginkgo, Radix Salviae Miltiorrhizae, Cordyceps mycelium, Bulbus Fritillariae Cirrhosae, Hirudo, Pheretima, the Rhizoma Anemarrhenae etc., have improving inspiration by invigorating kidney-QI astringe the lung relieving asthma, the effect of promoting blood circulation to remove obstruction in the collateral eliminating stagnation, cure mainly symptoms such as interstitial pulmonary fibrosis.The present invention has at first selected mixture according to the characteristics of its medication, and technology is easy, taking convenience, but clinical response and find the less stable of mixture in the practice process; The inventor is again according to modern patient's medication characteristics, preferably select for example oral solid formulation of tablet, because of each Chinese medicinal components of the present invention is to be used as medicine with the aqueous extract that obtains through extraction and the form of former powder, therefore it is fast to obey post-absorption, and it is easy and simple to handle, preparation stabilization, finished-product volume reduces, taking convenience.Through experimentation, preparation technology is easy, steady quality, controlled, preparation safety, effectively, the clinical verification effect is also good, so in a preferred embodiment of the invention, the dosage form of medicine of the present invention is defined as tablet.
The present invention also provides the preparation method of above-mentioned Chinese medicine composition, this preparation method is in many-sided factors such as the property of medicine of the comprehensive above-mentioned medicine of respectively distinguishing the flavor of, clinical, productions, consulting on the basis of documents and materials, physicochemical property, pharmacologically active in conjunction with the effective ingredient of each flavour of a drug, through repetition test research, the process route of the product of the present invention of design.
Therefore, the preparation method of Chinese medicine composition of the present invention comprises: the Chinese crude drug of Bulbus Fritillariae Cirrhosae, Radix Rhodiolae, Radix Notoginseng, Herba Erigerontis, Folium Ginkgo, Radix Salviae Miltiorrhizae, the Rhizoma Anemarrhenae decocts with water; The weight that adds water is 1-30 times of this Chinese crude drug weight, the decocting liquid that obtains, and add Cordyceps mycelium, Pheretima and hirugen powder, be this Chinese medicine composition.Also this decocting liquid drying can be obtained dried cream powder, and add Cordyceps mycelium, Pheretima and hirugen powder, be this solid-state Chinese medicine composition (or dried cream powder of title Chinese medicine composition).
The preferred for preparation method of above-mentioned Chinese medicine composition comprises: Chinese crude drugs such as Bulbus Fritillariae Cirrhosae, Radix Rhodiolae, Radix Notoginseng, Herba Erigerontis, Folium Ginkgo, Radix Salviae Miltiorrhizae, the Rhizoma Anemarrhenae decocted with water three times, was respectively heat time heating time 2 hours, and 1 hour, 1 hour; The weight that adds water is 1-26 times of this Chinese crude drug weight, is respectively 10 times, 8 times, and 8 times; Collecting decoction adds Cordyceps mycelium, Pheretima and hirugen powder, can obtain Chinese medicine composition of the present invention.Also this decocting liquid drying can be obtained dried cream powder, add Cordyceps mycelium, Pheretima and hirugen powder, be this solid-state Chinese medicine composition (or dried cream powder of title Chinese medicine composition).
General Chinese crude drug is used with decoction clinically substantially, and the method that adopts decocting to boil just can extract it substantially, does not therefore adopt alcohol precipitation process, thereby guarantees the curative effect of preparation.
Below be to be example, carry out the Orthogonal Experiment and Design of water extraction process with seven flavor medicines (crude drug amount 77g) such as Radix Notoginseng 15g, Radix Rhodiolae 10g, Bulbus Fritillariae Cirrhosae 6g, Folium Ginkgo 10g, Radix Salviae Miltiorrhizae 15g, Herba Erigerontis 15g Rhizoma Anemarrhenae 6g.
Through overtesting, investigate the factor that decocting boils that influences in many ways, select amount of water, extraction time, extraction time for to influence the main factor that decocting boils, and three reasonable level of corresponding selection are tested.Take by weighing totally 9 parts of seven flavor medicines such as Radix Notoginseng 15g, Radix Rhodiolae 10g, Bulbus Fritillariae Cirrhosae 6g, Folium Ginkgo 10g, Radix Salviae Miltiorrhizae 15g, Herba Erigerontis 15g, Rhizoma Anemarrhenae 6g, press L
9(3
4) orthogonal test table tests, and is controllability and the advance that guarantees product quality, to the index composition content of danshinolic acid B of the main test data paste-forming rate of reflection product quality and Radix Salviae Miltiorrhizae as investigating index.
The mensuration of paste-forming rate: after the medicinal liquid of every part of test gained concentrated, be settled to 100ml, shake up, the accurate 50ml that draws is transferred in the dry evaporating dish of having weighed, and water-bath is steamed near and done, and the baking oven of putting 70 ℃ carries out drying under reduced pressure to constant weight, calculates paste-forming rate.
The mensuration of content of danshinolic acid B: the employing high performance liquid chromatography (" an appendix VI of Chinese pharmacopoeia version in 2005 D), " assay " item method is down measured.
According to The results of analysis of variance of the present invention, extracting method does not have the significance influence to result of the test, in conjunction with producing practical situation, determines that the technology that decocting boils is: decoct with water 3 times, be respectively 10 times of amounts 2 hours; Measured 1 hour for 8 times; Measured 1 hour for 8 times.
Verify that by above-mentioned preparation technology experimental result and orthogonal experiments are close, illustrate that this extraction process stablizes feasible.
Cordyceps mycelium, Pheretima and Hirudo etc. are thin precious medicinal material in the side, consider himself characteristic, for reducing loss, give full play to the efficacy of a drug, thereby guarantee that the preparation stable curative effect is reliable, therefore adopt former powder to be used as medicine.
With medicine of the present invention is that tablet is an example, and the Financial cost of bound drug self-characteristic, preparations shaping standard and production needs, and adopts wet granulation, adds appropriate amount of auxiliary materials and makes tablet.
This preparation is a tablet, considers the cough that the crowd that takes of this medicine causes for accumulation of phlegm-damp in the lung, asthma, accumulation and obstruction of sputum and acute/chronic bronchitis patient.For making things convenient for it to take, and the Financial cost of factory's preparations shaping and production, add appropriate amount of auxiliary materials, adopt 80% ethanol wet granulation, tabletting, both.
Adopt wet granulation, the selection and the consumption of wetting agent are most important.At first draft the proportioning prescription, determine wetting agent and consumption, the results are shown in Table 1 by testing.
Table 1 wetting agent, ethanol consumption and concentration are to particulate influence
Conclusion: wetting agent is selected 80% ethanol, and addition is 5%.
According to many batches of tests, its average paste volume is 23.7%, both each recipe quantity powder 430g that approximately can get dry extract, add the former powder about 70g of part that is used as medicine, amount to about 500g, consider the factor of production and raw medicinal material, make total amount in order to adjust preparation, heavy with the supplementary product starch tab, so the sheet gravity treatment is selected as the 0.5g/ sheet.
Actual in conjunction with producing, the principle of saving manufacturing cost is considered from the finished product of preparation simultaneously, adds appropriate amount of auxiliary materials in semi-finished product, total amount is made in adjusting and sheet is heavy, and granule and the tabletting made all meet the requirements, and therefore adopts starch to adjust the semi-finished product amount, granulate tabletting, coating.
The present invention also provides the preparation method of the medicine of the treatment interstitial pulmonary fibrosis that contains above-mentioned Chinese medicine composition, and the preparation method of this medicine comprises: will comprise that Chinese crude drugs such as Bulbus Fritillariae Cirrhosae, Radix Rhodiolae, Radix Notoginseng, Herba Erigerontis, Folium Ginkgo, Radix Salviae Miltiorrhizae, the Rhizoma Anemarrhenae decoct with water; The weight that adds water is 1-26 times of this Chinese crude drug weight, and decocting liquid filters, and relative density was 1.30～1.35 thick paste when filtrate was concentrated into 60 ℃, added Cordyceps mycelium, Pheretima and Hirudo fine powder, and added the pharmacy acceptable auxiliary, got final product.
If said medicine is an oral dosage form, the preparation method of this medicine comprises: the Chinese crude drug that will comprise Bulbus Fritillariae Cirrhosae, Radix Rhodiolae, Radix Notoginseng, Herba Erigerontis, Folium Ginkgo, Radix Salviae Miltiorrhizae, the Rhizoma Anemarrhenae decocts with water; The weight that adds water is 1-26 times of this Chinese crude drug weight, decocting liquid filters, relative density was 1.30～1.35 thick paste when filtrate was concentrated into 60 ℃, added Cordyceps mycelium, Pheretima and Hirudo fine powder, and added the pharmacy acceptable auxiliary, mixing, spray is with alcohol granulation, drying, tabletting, coating promptly gets this medicine.
In a preferred embodiment of the invention, the preparation method of the medicine of the above-mentioned Chinese medicine composition of the described the present invention of containing comprises: seven kinds of Chinese crude drugs such as Bulbus Fritillariae Cirrhosae, Radix Rhodiolae, Radix Notoginseng, Herba Erigerontis, Folium Ginkgo, Radix Salviae Miltiorrhizae, the Rhizoma Anemarrhenae are decocted with water three times, be respectively heat time heating time 2 hours, 1 hour, 1 hour; The weight that adds water is 1-26 times of this Chinese crude drug weight, is respectively 10 times, 8 times, and 8 times; Collecting decoction filters, filtrate is concentrated into the thick paste that relative density is 1.30～1.35 (60 ℃), add Cordyceps mycelium, Pheretima and Hirudo fine powder, and add pharmacy acceptable auxiliary (for example dextrin is an amount of), mixing, spray is with 80% alcohol granulation, drying, granulate, tabletting, make 1000, promptly get medicine for the treatment of diseases such as interstitial pulmonary fibrosis of the present invention.
According to this area routine techniques, compositions of the present invention also can be made into honeyed pill, water-honeyed pill, the watered pill, paste pill, wax pill, concentrated pill, its processing step is routine operation, and visual medical material situation difference takes the circumstances into consideration to change process conditions, and it is conventionally known to one of skill in the art.
If medicine of the present invention is capsule, then the dried cream powder made of said method adds adjuvant, dextrin or also add or other binding agent for example, and abundant mixing, drying is pulverized, and incapsulates, promptly.
The Chinese crude drug that is adopted in the compositions of the present invention is the medical material that version pharmacopeia in 2005 is recorded, and through identifying, every index all meets the pharmacopeia regulation.
The inspection of arsenic salt and heavy metal in the medicine of the present invention: press one one of Chinese Pharmacopoeia version in 2005, the regulation under appendix IXE, the IXF item checks that to the arsenic salt and the heavy metal of this product 3 batch samples the result is in prescribed limit.
Health examination in the medicine of the present invention:, meet pharmacopeia hygiology standard through health examination.
The present invention also provides the application of above-mentioned Chinese medicine composition in diseases such as preparation treatment interstitial pulmonary fibrosis.
And the present invention also provides the application of said medicine in diseases such as preparation treatment interstitial pulmonary fibrosis.
Medicine of the present invention is example with the tablet, and clinical dosage is recommended as 2 slices/time, 3 times/day.
The pharmacology pharmacodynamic experimental study
It is generally acknowledged that bleomycin induced lung interstitial fibrosis pathological model is similar to people's interstitial pulmonary fibrosis pathological model
[1]So this experimentation adopts the method for injecting bleomycin in the trachea to duplicate the Pulmonary Fibrosis in Rats model, with this invention pharmaceutical intervention treatment, with prednisone as the positive treatment control drug, general situation of animal etc. is observed, alveolitis is observed in light microscopic hematoxylin-eosin (HE) dyeing, lung laminin, I, III collagen, hydroxyproline are observed in light microscopic trichroism (Masson) dyeing, and research lung moistening drink is to the influence of bleomycin Pulmonary Fibrosis in Rats model lung tissue pathology.
1 materials and methods
1.1 laboratory animal
The Waster rat, male, body weight 200 ± 20g is available from Beijing dimension tonneau China animal company.
1.2 main experimental drug
Bleomycin A5: 8mg/ props up, lot number: 050402 Tianjin Taihe county pharmaceutical Co. Ltd; Be mixed with 2mg/ml solution with normal saline.
Present composition granule (being called for short the lung moistening drink): each gram medicated powder is equivalent to crude drug 3.56 grams.
Prednisone: the 5mg/ sheet, Tianjin Lisheng Pharmaceutical Co., Ltd. produces, lot number: 0503019.
Anesthetis: 10% chloral hydrate.
0.9% normal saline: Beijing Co., Ltd of Double-Crane Pharmaceutical Co., Ltd produces.
2 experimental techniques
2.1 animal grouping
Conventional raising rat with 87 of rats, is divided into 4 groups by digital watch after one week at random, the A group: sham operated rats, without bleomycin but inject normal saline, not administration after the modeling is irritated the stomach normal saline, 15 during modeling.The B group: the animal model group, not administration after the bleomycin modeling is irritated the stomach normal saline, 24.The C group: the prednisone group gavages prednisone after the bleomycin modeling, 24.The D group: Chinese drug-treated group gavages lung fibre side medicated powder, 24 after the bleomycin modeling.
2.2 modeling
With 10% chloral hydrate 0.35ml/100g body weight, behind the intraperitoneal injection of anesthesia, dorsal position is fixed on the operating-table with rat, inserts No. 18 rat conduits through trachea, and thin cotton-wool is put into the tracheal intubation mouth, and thin cotton-wool is swung with rats breathing, the tracheal intubation success.Inject normal saline 1ml/kg body weight in the disposable trachea of sham operated rats, model group, prednisone group, Chinese drug-treated group are injected rich mycin A
51mg/kg injects air 0.3ml immediately, immediately that animal is upright, rotation after finishing, the clear-headed back of animal ad libitum access.
2.3 animal medicine feed
Modeling begins the conventional stomach method administration of irritating next day, once a day.Standard according to every 100g body weight administration 1ml prepares medicines.Weigh in weekly, adjust dosage according to body weight change.After body weight generally was increased to more than 400 grams, it was unlikely excessive to guarantee the administration volume to adjust liquor strength.
Chinese drug-treated group: people's lung fibre side dosage is 12.5 gram/days of medicated powder, and the equivalence metering that is equivalent to be grown up is got in the rat medication, and granule 1.25g/kg body weight in lung fibre side is equivalent to crude drug 4.45g/kg body weight, and liquor strength is 0.125g/ml.Prednisone group: prednisone 5mg/kg body weight.Liquor strength is 0.5mg/ml, uses normal saline as solvent.Model group and sham operated rats give isopyknic normal saline.
The grouping of table 2 laboratory animal, each organizes draw materials quantity, dosage
Annotate: the model group rat is dead 4 altogether in the experiment overall process, dead 2 altogether of prednisone groups, dead 0 of sham operated rats and lung fibre side groups of grains.
2.4 animal is handled
Put to death animal, each 5 of each random process sham operated rats, respectively 8 of model group, prednisone group, Chinese drug-treated group respectively at 14 days, 28 days, 45 days.
Use 10% chloral hydrate, 0.35ml/100g body weight, intraperitoneal injection of anesthesia rat.It is fixing that rat is lain on the back, and abdominal aortic blood is put to death animal, takes out lungs, left side lung places fixedly 24h of 4% paraformaldehyde, routine paraffin wax embedding, connective tissue's section (thick 4 μ m), carry out hematoxylin-eosin (HE) dyeing and trichroism (Masson) dyeing, light microscopic is observed lung tissue pathology down and is changed.The right lung lung is made lung homogenate liquid, gets the right lung tissue and prepares tissue homogenate in the ratio that the 100mg powder adds the 1mL normal saline, 3000 rev/mins, centrifugal 10 minutes, gets supernatant and measures.The aortic blood separation of serum ,-80 ℃ of refrigerator storage.
2.5 detection method
Carry out lung coefficient, lung tissue pathology morphological observation.
3 experimental results
3.1 lung coefficient
This experimental result shows: model group, prednisone group, lung moistening drink are organized three groups of each time point lung coefficients and all are significantly higher than sham operated rats, P＜0.01.There is not difference, P＞0.05 between same time point model group, prednisone group, lung moistening drink group group.Three time points compare on the same group, and the lung coefficient is the highest in the time of the 14th day, reduces gradually later on; Chinese medicine lung moistening drink group lung coefficient was lower than 14 days, P＜0.05 in the time of 28 days; But model group and prednisone group lung coefficient more just showed remarkable decline, P＜0.05 at the 48th day and 14 days.The result shows that the treatment of prednisone and lung moistening drink does not significantly reduce the induced lung coefficient, but Chinese medicine lung moistening drink group can reduce the induced lung coefficient in the short period of time.
3.2 lung tissue pathology
This experimental result shows: alveolitis is the most remarkable during with 14 days, and fibrosis obviously increases the weight of 45 days the time.Model group in the time of 14 days alveolitis the most remarkable; The alveolar inflammation dissipates (P＜0.05) than 14d in the time of 28 days, but fibrosis increases (P＜0.05); Alveolitis obviously dissipates (P＜0.05) during 42d, and fibrosis obviously increases (P＜0.05).
Alveolitis during with 14 days each group the most remarkable, alveolar septum broadening, inflammatory cell infiltration, as seen the macrophage of volume, lymphocyte, acidophil, the fracture of part alveolar, fusion, obturation, alveolar structure are destroyed obviously, lung tissue local visible large stretch of lumps inflammatory infiltration and fibrosis kitchen range.Respectively organized all more preceding dissipation of alveolitis in 28 days, respectively organize alveolitis in the time of 45 days and obviously dissipate, illustrate that rat has the function of self-regeneration.Pour into normal saline in the lung during sham operated rats modeling, a small amount of inflammatory exudation of alveolar space in the time of 14 days, surplus time point there is no unusually, and visible normal saline also has damaging action to lung.Prednisone group and lung moistening drink group alveolitis alleviate than model group in the time of 14 days, but not obvious at the statistical disposition group difference.Prednisone group and Chinese drug-treated group all are slight alveolitis in the time of 28 days, 45 days, and alveolar septum slightly thickens, and alveolar structure destroys light, and alveolitis all alleviates than model group, but group difference is not obvious after respectively organizing statistical disposition.
Sham operated rats does not have fibroplasia, and its excess-three group all has obvious fibroplasia.Lung fibroplasia is the lightest in 14 days, and alveolar septum broadening has fibroblast proliferation, and collagen fiber are a small amount of.The obvious broadening of alveolar septum in 28 days, a large amount of hypertrophy of fibroblast, collagen fiber form and the chronic inflammation cellular infiltration, and it is narrow that a small amount of interstitial lung thickens the compressing alveolar space.Alveolar wall significantly thickens in the time of 45 days, and a large amount of fibroplasia of matter is agglomerating in flakes between alveolar, alveolar structure destroys, the fibrosis cicatrization, and part pulmonary fibrosis intralesional has the bronchioles that differs in size of expansion, the part alveolar space disappears, the capillary lumen obturation, and the severe patient honeycomb lung occurs.Lack owing to fiber forms all in the time of 14 days, relatively do not have significant difference between model group, prednisone group, lung moistening drink group group.In the time of 28 days, prednisone group, the fibroplasia of lung moistening drink group alleviate than model group, and alveolar septum is thin, and less alveolar space to occur narrow; The fibroplasia of lung moistening drink group alleviates than model group, statistical disposition, and there is statistical significance P＜0.05; Lung moistening drink and prednisone group relatively do not have significant difference.The prednisone group is than the no significant difference of model group statistics.Prednisone group, the fibroplasia of lung moistening drink group alleviate than model group in the time of 45 days, and alveolar septum is thin, narrow, the no remarkable honeycomb lung of less alveolar space occurs.The fibroplasia of lung moistening drink group alleviates than model group, statistical disposition, and there is statistical significance P＜0.05; Lung moistening drink group alleviates than the prednisone group, statistical disposition, and there is statistical significance P＜0.05.The prednisone group is than the no significant difference of model group statistics.
From bleomycin induced lung pathological tissue model, prednisone group and lung moistening drink group all do not have the effect that significantly alleviates alveolitis, but the lung moistening drink is obvious than the prednisone group to alleviating the Pulmonary Fibrosis in Rats degree, illustrate that the lung moistening drink has the effect that collagen fiber form that suppresses, the lung moistening drink can alleviate the development of chronic phase pulmonary fibrosis.
3.3 laminin, I, III Collagen Type VI and hydroxyproline
The result shows: laminin content reduces than model group 14 days prednisone group, lung moistening drink group, but the statistics zero difference.The laminin content of 28 days prednisone groups, lung moistening drink group obviously reduces than model group, and there is remarkable statistical significance P＜0.05; Lung moistening drink group and prednisone group be zero difference relatively.The laminin content of 45 days prednisone groups, lung moistening drink group obviously reduces than model group, and there is notable difference P＜0.05; Lung moistening drink group and prednisone group compare, and there is notable difference P＜0.05.Illustrate that the lung moistening drink has reduced the laminin of bleomycin rat model, especially significantly at 45 days.
Result of study shows: type i collagen content all reduces than model group 14 days, 28 days, 45 days prednisone group, lung moistening drink group, and P＜there were significant differences for 0.05 statistics; 14 days, 28 days, 45 days lung moistening drink groups and prednisone group relatively, there were significant differences in P＜0.05.Illustrate that the lung moistening drink reduces type i collagen and is better than the hormone group.
The III Collagen Type VI all reduces than model group at 14 days prednisone group, lung moistening drink group content, P＜0.05, and there were significant differences for statistics; Lung moistening drink group and prednisone group compare, and there is notable difference P＜0.05.The III Collagen Type VI content of 28 days prednisone groups, lung moistening drink group obviously reduces than model group, and there is remarkable statistical significance P＜0.05; Lung moistening drink group and prednisone group compare, and there is notable difference P＜0.05.The III Collagen Type VI content of 45 days prednisone groups, lung moistening drink group obviously reduces than model group, and there is statistical significance P＜0.05; Lung moistening drink group reduces than prednisone group III Collagen Type VI content, P＞0.05 no significant difference.Explanation lung moistening drink reduces the III Collagen Type VI and is better than the hormone group, and is more outstanding at 14,28 days.
This experimental result shows: the 14th day, 28 days, 45 days each time point model group hydroxyproline contents and sham operated rats significantly raise, and prednisone group, lung moistening drink group and sham operated rats significantly raise.Three time point comparisons of model group hydroxyproline content raises gradually, prednisone group and lung moistening drink group in the time of 28 days hydroxyproline content the highest, reduce to some extent during to 45 days.14 days prednisone groups, lung moistening drink group and model group relatively do not have statistical significance.The hydroxyproline content of 28 days prednisone groups, lung moistening drink group reduces than model group, statistical significance is arranged, P＜0.01; Lung moistening drink group and prednisone group relatively do not have statistical significance.45 days prednisone group groups and model group be P＜0.05 relatively, and lung moistening drink group and model group comparison P＜0.01 have statistical significance; Lung moistening drink group and prednisone group compare, and there is statistical significance P＜0.05.The results suggest model group is existing tangible collagen fiber deposition in the time of the 14th day, interstitial pulmonary fibrosis forms, 28 days and comparison in 14 days, hydroxyproline content significantly raises, fibrosis increases the weight of, and hydroxyproline is still at high level in the time of 45 days, and prednisone group and lung moistening drink group reduce than model group at each time point collagen content, showed statistical significance in the time of 28 days, the treatment that prednisone and lung moistening drink is described is to suppressing Fibrotic certain meaning that is formed with.Show that relatively lung moistening drink group hydroxyproline content all reduces than model and prednisone group between group in the time of 45 days, statistical significance is arranged, illustrate that the lung moistening drink is better than prednisone to the effect that alleviates interstitial pulmonary fibrosis.
Interstitial pulmonary fibrosis is because turbid interior the giving birth to of impairment of dispersing and descending function of the lung expectorant, the deficiency of vital energy is unable agitates the capable then blood fortune of blood slow, and venation is lost in moistening and supported that then blood flow is not smooth, and stagnation and deficiency of QI, hematogenous blockage be the integrated expectorant of Tianjin blood clotting then, poly-form the stasis of blood, cause the condense pathological change of lung network of the turbid retardance of blood stasis expectorant thus.The lung moistening drink is made up of Cordyceps mycelia powder, Radix Notoginseng, Radix Rhodiolae, Folium Ginkgo, Radix Salviae Miltiorrhizae, Herba Erigerontis, Bulbus Fritillariae Cirrhosae, the Rhizoma Anemarrhenae, Pheretima, Hirudo, has the effect of nourishing lung and kidney, dissipating phlegm and resolving masses, promoting blood circulation to remove obstruction in the collateral, has anti-preferably interstitial pulmonary fibrosis effect.
Owing to there has been tangible CT to show that interstitial pulmonary fibrosis forms during interstitial pulmonary fibrosis patient clinical diagnosis, in clinical practice, suppress collagen fiber formation, reverse the progress of chronic phase pulmonary fibrosis, to quality of life of improving the patient, prolong the patient and life-span of surviving significant meaning is just arranged.Originally studies show that the lung moistening drink has significant inhibition fibroplasia effect to induced lung interstitial fibrosis lung tissue pathology, for clinical treatment provides favourable foundation.Conclusion:
In sum, the present composition is a compound Chinese medicinal preparation, clinically be used for the treatment of interstitial pulmonary fibrosis definite curative effect is arranged, and effect is better than similar medicine product, the result of clinical trial shows determined curative effect, safe and effective, long-time stability are investigated and are also shown, present composition steady quality, reliable.
The specific embodiment
For more clear explanation goal of the invention and technical scheme, be described in further detail by following embodiment.
Embodiment 1:
The prescription of compositions of the present invention:
Cordyceps mycelium 42g Herba Erigerontis 317g Radix Notoginseng 317g Radix Salviae Miltiorrhizae 317g
Radix Rhodiolae 211g Folium Ginkgo 211g Bulbus Fritillariae Cirrhosae 127g Hirudo 32g
Rhizoma Anemarrhenae 127g Pheretima 32g
Preparation method:
More than ten the flavor, get Cordyceps mycelium, Pheretima and Hirudo powder and be broken into fine powder, standby; Other gets seven flavors such as Herba Erigerontis, Radix Notoginseng, Radix Salviae Miltiorrhizae, Radix Rhodiolae, Folium Ginkgo, Bulbus Fritillariae Cirrhosae, the Rhizoma Anemarrhenae, decocts with water three times, filters, merging filtrate, being concentrated into relative density is the thick paste of 1.30-1.35 (60 ℃), adds Cordyceps mycelium, Pheretima and Hirudo fine powder, and adding pharmacy acceptable auxiliary (for example starch is an amount of), mixing, spray is with 80% alcohol granulation, drying, granulate, tabletting is made 1000, is compositions.
Embodiment 2:
Prescription:
Cordyceps mycelium 42g Herba Erigerontis 317g Radix Notoginseng 317g Radix Salviae Miltiorrhizae 317g
Radix Rhodiolae 211g Folium Ginkgo 211g Bulbus Fritillariae Cirrhosae 127g Hirudo 32g
Rhizoma Anemarrhenae 127g Pheretima 32g
Preparation method: preparation of compositions is with embodiment 1;
Capsule: in compositions, add starch, mixing, spray is with 80% alcohol granulation, and drying adds filler granulations such as magnesium stearate, and is encapsulated, promptly gets capsule of the present invention.
The result shows: present composition capsule meets the relevant every regulation under the capsule item.
Embodiment 3:
Prescription: 1 part of Bulbus Fritillariae Cirrhosae, Cordyceps mycelium 0.1-1.0 part, Radix Notoginseng 1.5-4 part, Radix Rhodiolae 1-3 part, Herba Erigerontis 1-5 part, Radix Salviae Miltiorrhizae 1-5 part, Folium Ginkgo 1-3 part, Hirudo 0.1-0.6 part, Rhizoma Anemarrhenae 1-5 part, Pheretima 0.1-0.6 part.
Preparation method:
More than ten the flavor, get Cordyceps mycelium, Pheretima and Hirudo powder and be broken into fine powder, standby; Other gets seven flavors such as Herba Erigerontis, Radix Notoginseng, Radix Salviae Miltiorrhizae, Radix Rhodiolae, Folium Ginkgo, Bulbus Fritillariae Cirrhosae, the Rhizoma Anemarrhenae, decoct with water three times, the weight that adds water is 1-26 times of this Chinese crude drug weight, is respectively 10 times, 8 times, 8 times, filter merging filtrate, being concentrated into relative density is the thick paste of 1.30-1.35 (60 ℃), add Cordyceps mycelium, Pheretima and Hirudo fine powder,, be compositions, and adding pharmacy acceptable auxiliary (for example starch is an amount of), mixing, spray is with 80% alcohol granulation, drying, granulate, tabletting is made 1000, promptly.
The result shows: present composition tablet meets the relevant every regulation under the tablet item.
Claims (9)
1. Chinese medicine composition, said composition is by following parts by weight of Chinese traditional medicine component: 1 part of Bulbus Fritillariae Cirrhosae, Cordyceps mycelium 0.1-1.0 part, Radix Notoginseng 1.5-4 part, Radix Rhodiolae 1-3 part, Herba Erigerontis 1-5 part, Radix Salviae Miltiorrhizae 1-5 part, Folium Ginkgo 1-3 part, Hirudo 0.1-0.6 part, Pheretima 0.1-0.6 part, Rhizoma Anemarrhenae 1-5 part, described Chinese medicinal components are above-mentioned Chinese crude drug fecula or the Chinese medicine extract that is equivalent to the crude drug amount of above-mentioned Chinese crude drug.
2. Chinese medicine composition as claimed in claim 1, wherein, described Cordyceps mycelium is the fermentation powder of Cordyceps fungus.
3. Chinese medicine composition as claimed in claim 1, wherein, described Chinese medicinal components is that aqueous extract and Cordyceps mycelium, Hirudo, the former powder of Pheretima of Bulbus Fritillariae Cirrhosae, Radix Rhodiolae, Radix Notoginseng, Herba Erigerontis, Folium Ginkgo, Radix Salviae Miltiorrhizae, the Rhizoma Anemarrhenae formed.
4. medicine for the treatment of interstitial pulmonary fibrosis is comprising each described Chinese medicine composition of claim 1-3 and pharmacy acceptable auxiliary.
5. medicine as claimed in claim 4, wherein, described medicine is a peroral dosage form, this peroral dosage form is honeyed pill, condensed water honeyed pill, the watered pill, granule, capsule, tablet, powder, unguentum, mixture or syrup.
6. medicine as claimed in claim 5, wherein, described medicine is granule, capsule, tablet or powder, described pharmacy acceptable auxiliary is arbitrary or its combination in microcrystalline Cellulose, starch, the dextrin; The weight of described pharmacy acceptable auxiliary accounts for the 0.15-50% of this drug weight.
7. the preparation method of the described medicine of claim 4, wherein, this method comprises: the Chinese crude drug of Bulbus Fritillariae Cirrhosae, Radix Rhodiolae, Radix Notoginseng, Herba Erigerontis, Folium Ginkgo, Radix Salviae Miltiorrhizae, the Rhizoma Anemarrhenae decocts with water; The weight that adds water is 1-30 times of this Chinese crude drug weight, decocting liquid filters, relative density was 1.30～1.35 when filtrate was concentrated into 60 ℃, added Cordyceps mycelium, Hirudo and Pheretima fine powder, and added the pharmacy acceptable auxiliary, mixing, spray is with alcohol granulation, drying, tabletting, coating promptly obtains this medicine.
8. the application of the described Chinese medicine composition of claim 1 in preparation treatment interstitial pulmonary fibrosis disease.
9. the application of the described medicine of claim 4 in preparation treatment interstitial pulmonary fibrosis disease.
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| CN106974928A (en) * | 2016-01-19 | 2017-07-25 | 上海国宝企业发展中心 | The purposes of cordycepin and preparation in preventing and treating organ fibrosis medicine and health-oriented products |
| CN112568188B (en) * | 2021-02-24 | 2021-05-25 | 澎立生物医药技术（上海）有限公司 | Method for preparing Brown Norway rat pulmonary fibrosis model |
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| CN1410096A (en) * | 2002-11-21 | 2003-04-16 | 杜仰恩 | Chinese patent medicine for treating primary lung cancer |
| CN101406626A (en) * | 2008-11-27 | 2009-04-15 | 王慧丽 | Oral medicament for treating pulmonary tuberculosis |
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| CN1410096A (en) * | 2002-11-21 | 2003-04-16 | 杜仰恩 | Chinese patent medicine for treating primary lung cancer |
| CN101406626A (en) * | 2008-11-27 | 2009-04-15 | 王慧丽 | Oral medicament for treating pulmonary tuberculosis |
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