CN108542962A - A kind of Chinese medicine composition and preparation method thereof for treating pulmonary fibrosis - Google Patents

Abstract

A kind of Chinese medicine composition and preparation method thereof for treating pulmonary fibrosis, belongs to technical field of traditional Chinese medicines, the purpose of the invention is to improve the symptoms such as the shortness of breath uncomfortable in chest caused by pulmonary fibrosis, chronic cough, takes the lung function that can also enhance patient for a long time.The composition of the present invention He Shui Lao roots form, is made of Radix Astragali, Radix Codonopsis, centella, eclipta, Cortex Phellodendri, ginkgo, American cockroach, Bell's charcoal, turtle shell by certain parts by weight proportioning.All medicine compatibilities, synergistic, drug activity significantly improves, and can reduce the content of HYP in pulmonary fibrosis mice lung tissue, and then treats pulmonary fibrosis and provide foundation for its clinical application.The present invention prepares simply, and good absorption effect is significant in efficacy, safe, is conducive to patient and mitigates symptom.

Description

A kind of Chinese medicine composition and preparation method thereof for treating pulmonary fibrosis

Technical field

It is a kind of that the present invention relates to a kind of Chinese medicine compositions and preparation method thereof for treating pulmonary fibrosis

Background technology

Pulmonary fibrosis（Pulmonary fibrosis, PF）It is acute and chronic interstitial lung disease caused by many reasons （Interstitial lung disease, ILD）Common final result, be the main pathological basis of respiratory failure, pathogenesis Unknown, pathological characteristic is the over-deposit that lung inflammation leads to the damage of alveolar duration and extracellular matrix；Clinical manifestation For progressive expiratory dyspnea, dry cough, tired, final generation hypoxemia and respiratory failure.PF disease packets silicosis, rheumatism lung, knot Fibrosis and a variety of lung diseases caused by section disease, drug, polyvinyl chloride and radioactive ray etc. develop to the common pathology in late period and become Change, it is very harmful to human life and health.

Recently as economic rapid development, ambient enviroment is destroyed, and it is difficult that haze has become China's urban landmark Topic, even more the PM2.5 contents in center, the livelihood issues paid high attention to down toward the common people, many urban airs severely exceed, Seriously endanger health.PM2.5 particles enter after nose, pharynx, larynx, and before entering blood, the structure of process is nose successively Chamber, pharynx, larynx, trachea-bronchial epithelial cell, haze have become an important factor for aggravating pulmonary fibrosis.The means for the treatment of pulmonary fibrosis at present The symptom of patient can only be mitigated, the survival rate of patient can not be made to make moderate progress.Not due to the pulmonary fibrosis cause of disease and pathogenesis It is fully apparent from, forms the complex process for further relating to many factors and multiple links such as cell, cell factor, ECM metabolism, treatment On acquire a certain degree of difficulty, still lack satisfied therapy at present.The incidence of pulmonary fibrosis in recent years is in rising trend, after making a definite diagnosis Mean survival time is 2~5 years, and 60% patient directly dies of the disease, although having been achieved both at home and abroad for the research of the disease Remarkable progress not yet finds the drug for curing pulmonary fibrosis so far, therefore, finds the medicine of new effective treatment pulmonary fibrosis Object becomes common the problem of paying close attention to both at home and abroad.

The Western medicine for the treatment of pulmonary fibrosis at present is mainly hormone and vasodilator class drug, such as prednisone, aminophylline, is relaxed Spirit etc. is breathed heavily, although rapid-action, is easy repeatedly, it is again big to take adverse reaction for a long time.In recent years, Treatment Pulmonary F ibrosis by Chinese Herbs by People's extensive concern also obtains certain effect.There is scholar to investigate Danhong Injection in Treating pulmonary fibrosis in the recent period.It is red The main component of red injection is Radix Salviae Miltiorrhizae and safflower.The former, which has, mitigates pulmonary edema, anti-fibrosis and fibrosis is promoted to absorb Function.Carthamin yellow in the latter can inhibit the development of pulmonary fibrosis.The experimental results showed that pellet is red to significantly improve lung work( Can, and improve the survival rate of patient.But it is more due to carrying out traditional Chinese medicine adverse reaction this year, cause it clinically cannot Extensive use.In addition, also many Chinese medicine preparations, have certain curative effect, but curative effect is satisfied not enough.

Invention content

The purpose of the invention is to provide a kind of Chinese medicine composition and preparation method thereof for treating pulmonary fibrosis.

The composition of the present invention is by Radix Astragali, Radix Codonopsis, centella, eclipta, Cortex Phellodendri, ginkgo, Bell's charcoal, turtle shell He Shui Lao Root totally 9 taste Chinese medicinal composition has ascending the clear and descending the turbid, inrigorating qi and promoting blood circulation, stagnation resolvation row stagnant and other effects, can be made into piece through modern preparation process Agent, capsule, pill, granule etc..It can be clinically used for the treatment of pulmonary fibrosis.

Radix Astragali nature and flavor in the present invention are sweet, tepor, return lung, spleen, liver and kidney channel.There are tonifying Qi and lifting yang, invigorating qi for consolidating superficies, Li Shui to disappear It is swollen, the effect of torr sore myogenic.From the dry root of pulse family perennial herb astragalus mongolicus or Astragalus membranacus.Slightly long with root item, Wrinkle is few, matter is hard and continuous, and mealiness foot, sweet person is preferred.The medicinal history of Radix Astragali has more than 2000 years so far, first appeared in tomb of Han dynasty horse Book copied on silk " 52 Bingfang " unearthed Wang Dui,《Sheng Nong's herbal classic》It is classified as top grade.《Collected statements on the herbal foundation》" Radix Astragali, tonifying lung invigorating the spleen, is defended load Real arrest sweating.”

Radix Codonopsis is sweet in flavor, mild-natured.Converge to the spleen channel, lung channel.With tonifying middle-Jiao and Qi, the effect of clearing heat and detoxicating, expelling phlegm and arresting coughing.The name of Radix Codonopsis begins See the Qing Dynasty《The new compilation of materia medica》, meaning：" by ancient herbal cloud：Ginseng palpus Shangdang person is good.”

Centella toil is trembled with fear.Enter liver,spleen,kidney warp.With clearing heat and promoting diuresis, the effect of removing toxicity for detumescence.Centella begins to carry《This warp》, History tree has description more.《Detailed outline》Careless portion volume 14 centella《Product in this warp》It is described in detail under item.[releasing name] has：Pennyroyal mint （《Tian Bao side》）, marchantia grass（《Tang Ben》）, Longtube Ground Ivy Herb（《Medicine figure》）.《Detailed outline lift is lost》In recorded desmodium.And cloud " detailed outline Have a centella, i.e., this.”

Eclipta acid sweet in flavor, it is cool in nature.Enter Liver Channel, kidney channel.Has effects that nourishing liver and kidney, cooling blood and hemostasis.This product be used as medicine first recorded in 《A thousand pieces of gold month》, original name Nanjing grass.《Tang materia medica》Name Eclipta prostrata, cloud：" give birth to wetland.Seedling is like sheathed a, alternanthera, place There is it between the canal of hole.”《Detailed outline》It carries：" the soft stem of Asian puccoon, disconnected has prepared Chinese ink to go out, and therefore named, custom exhales Mo Caishi.Thin real quite such as lotus pod shape, Therefore obtain lotus name.”

Cortex Phellodendri bitter, it is cold in nature.Return kidney, bladder warp, there is the effect of heat-clearing and damp-drying drug, purging intense heat, except steaming, detoxification sore treatment.Cortex Phellodendri first recorded in 《Sheng Nong's herbal classic》, original name " bark of a cork tree wood " is classified as top grade.《Mingyi Bielu》Claim cork tree, cloud：" raw Hanzhong mountain valley and Yongchang.”

Ginkgo is sweet in flavor, bitter, puckery；Mild-natured, mild toxicity.Distributed in lung channel, kidney channel.With astringing lung for relieving asthma；The effect of stop-band contracting urine.When Ming Dynasty Lee Treasure once said：" enters lung channel, beneficial temper, Dingchuan cough, reduces just." Qing Dynasty Zhang Lulu《This is through meeting source》Middle load gingko has drop phlegm, clear The function of poison, desinsection, can treat that " sore scabies subcutaneous ulcer tumor, acute mastitis fester, tooth worm dental caries, baby diarrhea, leukorrhea with reddish discharge, chronic stranguria with turbid discharge, something lost The diseases such as the smart enuresis ".Once there is the Chinese patent drug processed with gingko in the ground such as Ming Dynasty Jiangsu, Sichuan, for clinic.

Bell's charcoal is cold in nature, sour, bitter；It is slightly poisonous.With easypro liver, promoting qi circulation and relieving pain, the effect of expelling parasite.For Meliaceae deciduous tree The dry mature fruit of toosendanin.It is a kind of common native Sichuan crude drugs, first recorded in《Sheng Nong's herbal classic》.

Turtle shell is salty, is slightly cold.Return liver warp, kidney channel.With nourishing Yin and clearing heat, the effect of checking exuberance of yang relieves dizziness, high fever, infantile convulsions, epilepsy, etc., softening and resolving hard mass；It is dynamic for Trionychidae The carapace of object soft-shelled turtle.Begin to carry《Sheng Nong's herbal classic》, it is classified as middle product.

Shui Lao roots acrid flavour, hardship, sweet, gas is smelly, cold in nature.With subdhing swelling and detoxicating, clearing heat and promoting diuresis, diuresis, expelling wind and clearing away cold, analgesic, Antipruritic effect.Come from《Tang materia medica》.

All medicine phases 5, the effect of playing ascending the clear and descending the turbid, inrigorating qi and promoting blood circulation, stagnant stagnation resolvation row altogether.

Major function：Ascending the clear and descending the turbid, inrigorating qi and promoting blood circulation, stagnation resolvation row are stagnant.It has difficulty in breathing for progressive, with dry cough or coughs up The diseases such as shortness of breath after phlegm, physical exertion.Above-mentioned disease person is shown in pulmonary fibrosis.

The dosage form of the composition is one or more of tablet, capsule, pill and granule.

Application of the pharmaceutical composition in preventing and treating pulmonary fibrosis.

The advantageous effect that the present invention is reached：

Composition provided by the present invention can reduce IL-1, IL-6 and TNF-α content in pulmonary fibrosis model rat blood serum. TNF-α is a kind of important inflammatory mediator, either interstitial lung disease patient or animal model, the TNF-α of AM releases Increase.Therefore, TNF-α is an important indicator of clinical examination pulmonary fibrosis.TNF-α membrane receptor has TNF-R1 and TNF-R2 Two types.When TNF-α is combined with membrane receptor, NF- κ B and the MAPK accesses of intracellular are activated, adjust genetic transcription, generation includes Cytokine profiles including TGF-β, IL-1 and IL-6.

Also, composition provided by the present invention can reduce hydroxyproline in pulmonary fibrosis model lung tissue of rats Content, and there is significant difference（P<0.01）, i.e., composition provided by the present invention has inhibiting effect to pulmonary fibrosis.

Therefore, a kind of composition provided by the present invention, including Radix Astragali, Radix Codonopsis, centella, eclipta, Cortex Phellodendri, ginkgo, Bell's charcoal, turtle shell He Shui Lao roots, with hydroxyproline in inflammatory factor in reduction pulmonary fibrosis model rat blood serum and lung tissue Content, and can have the function that prevent and treat pulmonary fibrosis.

Specific implementation mode

Specific implementation mode one：

The content of present invention is not limited only to the content of the respective embodiments described above, the group contract of one of them or several specific implementation modes Sample can also realize the purpose of invention.

Beneficial effects of the present invention are verified by following embodiment：

Embodiment 1

1 material

1.1 experimental animal

Healthy SD rat, male, cleaning grade, 220~260 g of weight, by Heilongjiang University of Chinese Medicine's drug safety evaluation The heart（GLP）It provides, animal uses credit number：SCXK2014-004, room temperature raising, drinking-water of freely ingesting.

1.2 experimental drug

A kind of Chinese medicine composition for treating pulmonary fibrosis of the present invention（Tablet is made in the composition of the present invention）, positive drug acetic acid Prednisone（Xuzhou zero diopter Pharmaceutical Co）, 0.9% sodium chloride injection（Three medicine company share of Harbin is limited Company, batch number：171002D11）, bleomycin（The bio tech ltd Suo Baolai）, 10% chloraldurate（Tianjin Good fortune morning chemical reagent factory, lot number：20170907）, hydroxyproline（Hyp）Assay kit（Bio-engineering research is built up in Nanjing Institute）, mouse Interleukin -1β（mouse IL-1β）, mouse interleukin-6（mouse IL-6）, murine tumor necrosis factor-α （mouse TNF-α）ELISA kit is purchased from Wuhan Boster Biological Technology Co., Ltd..

1.3 key instrument

UV-1800 ultraviolet specrophotometers（Japanese Shimadzu）；KDC-160R high speed refrigerated centrifuges（The limited public affairs of University of Science and Technology's Innovations Si Zhongjia branch companies）；CPA225D electronic analytical balances（Sai Duoli scientific instrument north Co., Ltd）；Multi Skan3 enzyme marks Instrument（Thermo）；- 80 DEG C of ultra low temperature freezers（Thermo）.

2 methods

2.1 animal packets and administration

60 SD rats are randomly divided into 5 groups, i.e. model group, Normal group, positive drug group, Chinese medicine composition high and low dose Group, every group 12.Positive drug group gives prednisone acetate（3.34mg·kg^-1）, traditional Chinese medicine composition for treating high and low dose group difference Chinese medicine composition decocting liquid 4.16g/kg, 1.04g/kg of the present invention is given, model group and Normal group give normal salt Water, each group continuous gavage are administered 28 days.

It is prepared by 2.2 animal models

4% chloraldurate of experimental rat（0.01mL/g）After anesthesia, sterile working downlink neck median incision, exposure tracheae.Model Group and treatment group's tracheal strips Injecting Bleomycin after Retaining（5mg·kg-1）0.2~0.3mL of aqueous solution, Normal group inject equivalent life Reason brine makes liquid be uniformly distributed in intrapulmonary, then sews up the incision as possible by rat vertical rotary 30s after injection.

2.3 method of drawing material

Point 2 materials, each each group take rat 6 at random after being administered the 14th, 28 day, and ip gives 4% chloraldurate（0.01 mL/g）After anesthesia, vena portae hepatica takes blood, detaches serum, is stored in -80 DEG C of ultra low temperature freezers, for ELISA detections IL-1 β, IL-6 and TNF-α.Right lung is taken to be fixed with 10% formalin, routine paraffin wax embedding, slice, row HE dyeing and Masson are dyed.It is left Lung is preserved in -80 DEG C of ultra low temperature freezers, is used for Hyp assays.

2.4 Testing index

2.4.1 pathologic morphological observation

Pathological section row HE dyeing and Masson dyeing, light microscopic observation Histopathologic changes simultaneously take the photograph piece, with reference to Szapiel etc. Method evaluates each group lung tissue of rats pulmonary alveolitis degree and pulmonary fibrosis degree.HE dyeing evaluation lung tissue alveolar inflammation degree, 0 point：Without lung tissue inflammation；1 point：Slight lung tissue is scorching, and inflammatory cell infiltration is only limitted to part or nearly pleura portion, area are less than full lung 20%；2 points：Moderate lung tissue is scorching, and involvement area accounts for the 20%~50% of full lung；3 points：Severe lung tissue is scorching, and involvement area is big In 50%.Masson dyeing evaluation lung fibrosis degree, 0 point：Without pulmonary fibrosis；1 point：Slight pulmonary fibrosis, area of being involved Less than full lung 20%；2 points：Moderate pulmonary fibrosis, involvement area account for 20%~50%；3 points：Severe pulmonary fibrosis, involvement area are big In 50%, alveolar structure is disorderly.

2.4.2 IL-1 β, IL-6 and TNF-α Concentration Testing in serum

In strict accordance with Double antibody sandwich-ELISA（ELISA）Kit specification is operated.

2.4.3 hydroxyproline in lung tissue（Hyp）The measurement of content

Appropriate left lung homogenate, centrifugation is taken supernatant to be extracted, in strict accordance with hydroxyproline（Hyp）Testing cassete specification carries out Operation.

2.5 data processing

Using 0 softwares of SPSS19., data indicate that more comparison among groups use one-way analysis of variance, with P ＜ using `x ± s 0.05 is statistically significant for difference.

3 results

3.1 pathologic morphological observations

Normal group lung tissue structure is normal, and alveolar structure is clear, and water proof is swollen continuously, inflammatory cell infiltration and Collagen fiber deposition； The 14th day pulmonary alveolitis of model group is apparent, and alveolar structure is disorderly, visible a large amount of inflammatory cell exudations in alveolar, fibroblast proliferation, Large-area fibre lesion, the 14th, the 28 day gradual unobvious of pulmonary alveolitis, but pulmonary fibrosis degree is formed to aggravate in progressive；Mould Type group alveolar is scorching and pulmonary fibrosis degree is in different time points obviously higher than normal group of the same period, and difference is apparent（P ＜ 0. 01）；Compared with model group, present composition high and low dose group lung tissue pulmonary alveolitis and pulmonary fibrosis degree have different journeys The improvement of degree（P ＜ 0.01 or P ＜ 0.05）.Concrete outcome is shown in Table 1.

Influence of 1 present composition of table to alveolar inflammation and pulmonary fibrosis degree（`x ± s, n=12）

Note：1) the P ＜ 0.01 compared with normal group；2) the P ＜ 0.01,3 compared with model group) P ＜ 0.05（Table 2~3 is same）.

The level of inflammatory factor IL-1 β, IL-6 and TNF-α in 3.2 rat blood serums

Compared with normal group, the level of the 14th, 28 day model group rats serum inflammatory factor IL-1 β, IL-6 and TNF-α has It increases, there is statistical significance（P<0.01）；Compared with model group, the 14th, 28 day Chinese medicine composition high and low dose of the invention The level of inflammatory factor IL-1 β, IL-6 and TNF-α has reduction in group rat blood serum（P ＜ 0.01 or P ＜ 0.05）.Tool Body is shown in Table 2.

Influence of 2 present composition of table to rat blood serum inflammatory factor IL-1 β, IL-6 and TNF-α（`x ± s, n=12, ng/L）

3.3 lung tissue hydroxyproline contents measure

At the 14th, 28 day, compared with blank control group, Hyp was significantly increased in model group rats lung tissue（P ＜ 0.01）；With mould Type group is compared, and the content of Hyp has reduction in Chinese medicine composition high and low dose group lung tissue of rats of the invention（P ＜ 0.01 Or P ＜ 0.05）.Concrete outcome is shown in Table 3.

Influence of the 3 tonifying lung dissolving stasis side of table to lung fibrosis in rats lung tissue Hyp（N=6, `x ± s, mg/g）

Therefore, Chinese medicine composition of the invention causes bleomycin pathologic state, the inflammatory factor of Model of Bleomycin-induced Pulmonary Fibrosis And hydroxyproline content has apparent adjustment effect, has some improvement to lung fibrosis in rats tool.

Embodiment 2

Clinical trial

1 clinical data and method

1.1 case selection

Pulmonary fibrosis patients 86 are chosen, are randomly divided into 2 groups.Treatment group 46.Age is 55 years old average at 40 ~ 70 years old；Control group 40, the age is 60 years old average at 45 ~ 75 years old.Two groups of patient's general information include gender, age, symptom etc. without significance difference It is different（P ＞ 0.05）, it is comparable.

1.2 therapy

A kind of oral the of the present invention for the treatment of group treats pulmonary fibrosis Chinese medicine composition, takes orally, 2 times a day, the course for the treatment of 1 month.

Control group takes orally prednisone acetate, each 10mg, one time a day.The course for the treatment of 1 month.

2 criterions of therapeutical effect and treatment results

2.1 criterion of therapeutical effect

Diagnostic criteria is issued according to respirology branch of Chinese Medical Association 2002-2004《Idiopathic lung（Interstitial）Fibrosis is examined Disconnected and treatment guidelines（Draft）》And《National standard application-tcm internal medicine disease conventional treatment》It formulates.

（1）It is effective：Clinical symptoms control, and lung's rale is slight or substantially reduced with cyanosis, mobility enhancing；Chest X The inspections such as line or CT inspections, lung function, arterial blood gas are clearly better, and symptom integral reduces >=70%.

（2）Effectively：Clinical symptoms make moderate progress, sign mitigates, chest X lines or CT inspections, lung function, arterial blood gas inspection It looks into and take a favorable turn, life can take care of oneself substantially.Symptom integral reduces >=30%.

（3）In vain：Clinical symptoms, sign without change or are aggravated without improvement, chest X lines or CT inspections, arterial blood gas.Disease Shape integral is reduced less than 30%.Treatment statistics are shown in Table 1.

1 two groups of patient clinical total effects of table compare [example,（%）]

Group	Case load	Recovery from illness	Effectively	In vain	Total effective rate（%）	Obvious adverse reaction example
							Treatment group	46	40	2	4	91%	0
Control group	40	23	5	12	70%	0

As shown in Table 1, the Chinese medicine composition drug of present invention treatment pulmonary fibrosis can safely and effectively treat pulmonary fibrosis, cure Rate is higher.

Claims (8)

1. a kind of Chinese medicine composition for treating pulmonary fibrosis, it is characterised in that the Chinese medicine composition is by 5 ~ 15 parts in parts by weight Radix Astragali, 35 ~ 45 parts of Radix Codonopsis, 10 ~ 20 parts of centellas, 25 ~ 35 portions of ecliptas, 25 ~ 35 portions of Cortex Phellodendris, 10 ~ 20 portions of ginkgoes, 5 ~ 15 parts of U.S.s The big Lian in continent, 5 ~ 15 parts of Bell's charcoals, 5 ~ 15 parts of turtle shells and 25 ~ 35 Fen Shui Lao roots composition.

2. a kind of Chinese medicine composition for treating pulmonary fibrosis according to claim 1, it is characterised in that it is in parts by weight It is by 5 ~ 10 parts of Radix Astragalis, 35 ~ 40 parts of Radix Codonopsis, 10 ~ 15 parts of centellas, 25 ~ 30 portions of ecliptas, 25 ~ 30 portions of Cortex Phellodendris, 10 ~ 15 parts of silver Apricot, 5 ~ 10 portions of American cockroaches, 5 ~ 10 parts of Bell's charcoals, 5 ~ 10 parts of turtle shells and 25 ~ 30 Fen Shui Lao roots composition.

3. a kind of Chinese medicine composition for treating pulmonary fibrosis according to claim 1, it is characterised in that it is in parts by weight It is by 10 ~ 15 parts of Radix Astragalis, 40 ~ 45 parts of Radix Codonopsis, 15 ~ 20 parts of centellas, 30 ~ 35 portions of ecliptas, 30 ~ 35 portions of Cortex Phellodendris, 15 ~ 20 parts of silver Apricot, 10 ~ 15 portions of American cockroaches, 10 ~ 15 parts of Bell's charcoals, 10 ~ 15 parts of turtle shells and 30 ~ 35 Fen Shui Lao roots composition.

4. a kind of Chinese medicine composition for treating pulmonary fibrosis according to claim 1, it is characterised in that it is in parts by weight It is by 10 ~ 12 parts of Radix Astragalis, 40 ~ 42 parts of Radix Codonopsis, 15 ~ 18 parts of centellas, 30 ~ 32 portions of ecliptas, 30 ~ 32 portions of Cortex Phellodendris, 15 ~ 18 parts of silver Apricot, 10 ~ 12 portions of American cockroaches, 10 ~ 12 parts of Bell's charcoals, 10 ~ 12 parts of turtle shells and 30 ~ 32 Fen Shui Lao roots composition.

5. a kind of Chinese medicine composition for treating pulmonary fibrosis according to claim 1, it is characterised in that it is in parts by weight It is by 10 parts of Radix Astragalis, 40 parts of Radix Codonopsis, 15 parts of centellas, 30 portions of ecliptas, 30 portions of Cortex Phellodendris, 15 portions of ginkgoes, 10 parts of American cockroaches, 10 Part Bell's charcoal, 10 parts of turtle shells and 30 Fen Shui Lao roots composition.

6. the pharmaceutical composition for the treatment of pulmonary fibrosis according to claim 1, it is characterised in that：The dosage form of the composition For one or more of tablet, capsule, pill, granule.

7. the pharmaceutical composition for the treatment of pulmonary fibrosis according to claim 1, it is characterised in that：It is used clinically for preventing With treatment pulmonary fibrosis.

8. application according to claim 7, it is characterised in that：The Chinese medicine composition is for preventing and treating long-term suction Cigarette, the pulmonary fibrosis that extraneous poor environment influences and chronic bronchitis induces.