CN106074719A - Plumula Nelumbinis extract is in the application of preparation treatment pulmonary fibrosis medicine - Google Patents
Plumula Nelumbinis extract is in the application of preparation treatment pulmonary fibrosis medicine Download PDFInfo
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Abstract
The invention discloses the Plumula Nelumbinis extract application in preparation treatment pulmonary fibrosis medicine.In the present invention, involved Chinese medicine Plumula Nelumbinis is the integration of edible and medicinal herbs kind that Ministry of Public Health is promulgated, experiment proves: Plumula Nelumbinis extract can substantially suppress the HELF cell proliferation induced by TGF β 1；Significantly reducing the content of TGF β 1 in the mice serum of bleomycin induction, in the mice lungs of suppression bleomycin induction, the expression of HYP, MDA, significantly improves bleomycin induced mice pulmonary fibrosis, and pulmonary fibrosis treatment is had definite curative effect.Compared with existing anti-fibrosis drug, safety non-toxic has no side effect.
Description
Technical field
The present invention relates to drug world, relate to the application in preparation treatment pulmonary fibrosis medicine of a kind of Plumula Nelumbinis extract.
Background technology
Idiopathic pulmonary fibrosis (IPF) be caused by multiple inducement pneumonia reaction, alveolar persistence damage and
Extracellular matrix is repeatedly destroyed, repairs, rebuilds, thus causes excessive matrix deposition, ultimately cause lung tissue structure change and
The class disease that pulmonary function is lost.Clinical manifestation is dry cough, Progressive symmetric erythrokeratodermia dyspnea, runs down to exhaustion through several months or several years
Or it is dead.
In recent years, global range IPF sickness rate presents and rises situation year by year.NIH (NIH) website
The data that in June, 2012 announces show, American I PF patient reaches 500,000 people, and increases patient 50,000 people the most every year newly, every year
40,000 people are had to die from this disease.Britain IPF patient is about 13.2 ten thousand～200,000 people, and IPF sickness rate increases with the speed of annual about 11%
Long.8～8.5 ten thousand patients are had at present in Europe.It is 5/,100,000 annual, according to Chinese Medical Association's respiratory disease at China's IPF sickness rate
Branch's ID group is to the Patients during Hospital Ward investigation of family of China more than ten, and the patient of IPF presents the trend increased year by year equally.
The life of IPF serious harm patient and quality of life, this disease has the spy that the state of an illness drastically deteriorates, the time-to-live is short, case fatality rate is high
Point.Patient is along with the development of the state of an illness, and pulmonary function is gradually reduced to such an extent as to day by day limits the daily routines of patient, after the day certainly made a definite diagnosis
The mean survival time of patient is typically 2～5 years, and within 5 years, survival rate only has 20%.
Having inflammatory and immune response to participate in the formation of interstitial pulmonary fibrosis, therefore glucocorticoid and immunosuppressant are to pass
Ruling the medicine treating pulmonary fibrosis, they can suppress inflammatory reaction and immunologic process, alleviates alveolar inflammation, thus delays lung fine
The process of dimensionization.But study discovery recently, glucocorticoid is only effective to the IPF patient of 20%, and long-term taking sugar skin
Matter hormone often merges antibacterial or the fungal infection of pulmonary, there is significantly local and systemic side effects.Immunosuppressant warp
Often use does not only exist potential serious side effects, and the most invalid to IPF treatment.Along with the development of China's Chinese medicine and pharmacy,
Discovered in recent years many Chinese medicine monomer compositions or compound recipe have significant curative effect, treatment by Chinese herbs lung fiber on pulmonary fibrosis is treated
The scheme changed obtains extensive concern, and therefore finding novel low toxicity Effective Anti pulmonary fibrosis medicine from Chinese medicine becomes study of pharmacy
Important topic.
Summary of the invention
It is an object of the invention to overcome the deficiencies in the prior art, it is provided that Plumula Nelumbinis extract is at preparation treatment pulmonary fibrosis medicine
The application of thing.
Technical scheme is summarized as follows:
Plumula Nelumbinis extract is in the application of preparation treatment pulmonary fibrosis medicine.
Preparation containing Plumula Nelumbinis extract is in the application of preparation treatment pulmonary fibrosis medicine.
The dosage form of described preparation is granule, tablet, hard capsule, soft capsule, pill, oral liquid, effervescent tablet, dispersion
Sheet, drop pill or syrup.
Advantages of the present invention: in the present invention, involved Chinese medicine Plumula Nelumbinis is the integration of edible and medicinal herbs kind that Ministry of Public Health is promulgated, experiment
Prove: Plumula Nelumbinis extract can substantially suppress the HELF cell proliferation induced by TGF-β 1；Significantly reduce bleomycin induction
Mice serum in the content of TGF-β 1, in the mice lungs of suppression bleomycin induction, the expression of HYP, MDA, significantly improves rich
Bleomycin induced mice pulmonary fibrosis, has definite curative effect to pulmonary fibrosis treatment.With existing anti-fibrosis drug phase
Ratio, safety non-toxic has no side effect.
Accompanying drawing explanation
Fig. 1 is that the Plumula Nelumbinis extract various dose gastric infusion of embodiment 6 preparation is to pulmonary fibrosis mice lung tissue disease
Reason impact (HE dyeing)
Wherein A: Normal group B: model group C: positive controls D: high dose group E: middle dosage group F: low dose group.
Fig. 2 is that the Plumula Nelumbinis extract various dose gastric infusion of embodiment 6 preparation is to pulmonary fibrosis mice lung tissue disease
Reason impact (masson dyeing)
Wherein A: Normal group B: model group C: positive controls D: high dose group E: middle dosage group F: low dose group.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is further illustrated.Example below is used for further illustrating this
Bright but be not limited to the present invention.All technology realized based on foregoing of the present invention belong to the scope of the invention.
Plumula Nelumbinis extract, makes by following method:
1) Plumula Nelumbinis pulverizing medicinal materials；
2) by weight the ratio for 1:8-10, Plumula Nelumbinis water or volumetric concentration after pulverizing are 30%-85%'s
Ethanol water heating and refluxing extraction 2-4 time, each 0.5-1.5 hour, concentrating under reduced pressure obtained extractum, lyophilization, and lyophilized powder is
Plumula Nelumbinis extract.
The relative density of above-mentioned extractum is 1.30-1.35.
Embodiment 1
The extracting method of Plumula Nelumbinis extract, comprises the steps:
1) Plumula Nelumbinis pulverizing medicinal materials；
2) the Plumula Nelumbinis use water heating and refluxing extraction after pulverizing 3 times, each 1 hour, merging filtrate, concentrating under reduced pressure obtained phase
Being the extractum of 1.35 to density, lyophilization, lyophilized powder is Plumula Nelumbinis extract.
Extracting for 3 times, water is that the times of weight being extracted material is followed successively by 10,8,8.
Embodiment 2
The extracting method of Plumula Nelumbinis extract, comprises the steps:
1) Plumula Nelumbinis pulverizing medicinal materials；
2) the Plumula Nelumbinis volumetric concentration after pulverizing is 30% ethanol water, and heating and refluxing extraction 4 times is each 1 little
Time, merging filtrate, concentrating under reduced pressure obtains the extractum that relative density is 1.30, lyophilization, and lyophilized powder is Plumula Nelumbinis extract.
Extracting for 4 times, 30% ethanol water is that the times of weight being extracted material is followed successively by 10,8,8,8.
Embodiment 3
The extracting method of Plumula Nelumbinis extract, comprises the steps:
1) Plumula Nelumbinis pulverizing medicinal materials；
2) the Plumula Nelumbinis volumetric concentration after pulverizing is 50% ethanol water, heating and refluxing extraction 4 times, each 0.5
Hour, merging filtrate, concentrating under reduced pressure obtains the extractum that relative density is 1.30, lyophilization, and lyophilized powder is Plumula Nelumbinis extract.
Extracting for 4 times, 50% ethanol water is that the times of weight being extracted material is followed successively by 10,8,8,8.
Embodiment 4
The extracting method of Plumula Nelumbinis extract, comprises the steps:
1) Plumula Nelumbinis pulverizing medicinal materials；
2) the Plumula Nelumbinis volumetric concentration after pulverizing is 60% ethanol water, and heating and refluxing extraction 3 times is each 1 little
Time, merging filtrate, concentrating under reduced pressure obtains the extractum that relative density is 1.35, lyophilization, and lyophilized powder is Plumula Nelumbinis extract.
Extracting for 3 times, 60% ethanol water is that the times of weight being extracted material is followed successively by 10,8,8.
Embodiment 5
The extracting method of Plumula Nelumbinis extract, comprises the steps:
1) Plumula Nelumbinis pulverizing medicinal materials；
2) the Plumula Nelumbinis volumetric concentration after pulverizing is 70% ethanol water, and heating and refluxing extraction 3 times is each 1 little
Time, merging filtrate, concentrating under reduced pressure obtains the extractum that relative density is 1.32, lyophilization, and lyophilized powder is Plumula Nelumbinis extract.
Extracting for 3 times, 70% ethanol water is that the times of weight being extracted material is followed successively by 10,8,8.
Embodiment 6
The extracting method of Plumula Nelumbinis extract, comprises the steps:
1) Plumula Nelumbinis pulverizing medicinal materials；
2) the Plumula Nelumbinis volumetric concentration after pulverizing is 85% ethanol water, heating and refluxing extraction 2 times, each 1.5
Hour, merging filtrate, concentrating under reduced pressure obtains the extractum that relative density is 1.34, lyophilization, and lyophilized powder is Plumula Nelumbinis extract.
Extracting for 2 times, 85% ethanol water is that the times of weight being extracted material is followed successively by 8,8.
Embodiment 7
Plumula Nelumbinis extract embodiment 1 prepared, adds appropriate dextrin, mix homogeneously, adds volumetric concentration 70% second
Alcohol-water solution is a little, makes soft material, crosses 14 mesh sieves and pelletizes, and wet granular is dried in 60 DEG C, and dry granule crosses 14 mesh sieve granulate, after 4
Number sieve sieve take fine powder, obtain granule.
Embodiment 8
Plumula Nelumbinis extract embodiment 2 prepared, adds appropriate lactose, mixing, water-soluble with volumetric concentration 95% ethanol
Liquid is pelletized, and is dried, and loads capsule, makes hard capsule.
Embodiment 9
Plumula Nelumbinis extract embodiment 3 prepared, adds proper honey, mix homogeneously, makes pill.
Embodiment 10
Plumula Nelumbinis extract embodiment 4 prepared, adds citric acid, sodium bicarbonate, stevioside, xylitol mixing,
Pelletize with dehydrated alcohol, be dried, add magnesium stearate, mixing, tabletted, obtain effervescent tablet.
Embodiment 11
Plumula Nelumbinis extract embodiment 5 prepared, adds cellulose, microcrystalline Cellulose, calcium bicarbonate mixing, uses volume
Concentration is that 50% ethanol water is pelletized, and is dried, tabletted, obtains dispersible tablet.
Embodiment 12
Plumula Nelumbinis extract embodiment 6 prepared, adding volumetric concentration is that 95% ethanol water makes alcohol content reach
50%, cold preservation stands overnight, and takes supernatant, concentrates, and adds appropriate sodium benzoate, sorbitol, tween 80, sucrose, and stirring is mixed
Closing uniformly, add water constant volume, filters, subpackage, sterilizing, obtains oral liquid.
Routine techniques means can also be used to prepare tablet, soft capsule, drop pill or syrup.
Pharmacological experimental example
One, Plumula Nelumbinis extract becomes the impact of fiber (HELF) cell proliferation to the human embryo lung (HEL) that TGF-β 1 is induced
1. experimental technique:
HELF cell is incubated in the DMEM culture medium containing 10% hyclone, within every 2～3 days, passes on 1 time, growth of taking the logarithm
Phase HELF cell is inoculated in 96 orifice plates (8000, every hole cell), sucks culture medium after cultivating 24h.Model group and pharmaceutical intervention group
Adding TGF-β 1 (final concentration of 1ng/ml) to stimulate, pharmaceutical intervention group is simultaneously introduced medicine (final concentration of 0.1mg/ml),
Fully mixing, after hatching 48h, every hole adds the tetrazolium bromide (MTT, 5mg/ml) of 10ul, continues to hatch 4 hours.Discard after 4 hours
Supernatant, adds 150ul DMSO, and vibrate 10min, and upper microplate reader detects absorbance (OD) value in each hole.
2. experimental result
The impact of the HELF propagation that TGF-β 1 is induced by table 1 Plumula Nelumbinis extract
*p<0.05；* P < 0.01 compares with model group
Two, the Plumula Nelumbinis extract intervention effect to pulmonary fibrosis model mice
1. laboratory animal: kunming mice, male, body weight 18～20g, by Military Medical Science Institute's Animal Experimental Study center
There is provided, animal productiong credit number: SCXK-(army)-007.
2. animal model makes
(1) animal packet: experiment mice divides 12 groups at random, often group 10.It is set to blank group, bleomycin mould
Type group, positive controls [dexamethasone (Tianjin KingYork Amino Acid Co., Ltd.'s production)] and administration group (by embodiment 1,2,6 points
Do not prepare high, medium and low dosage group).
(2) modeling method: use disposable trachea instillation to make mouse pulmonary fibrosis model.Each group mouse peritoneal injection
100mg/kg pentobarbital 0.04ml anaesthetizes, and takes fixed bit of lying on the back, routine disinfection, row cervical region median incision, and blunt separation exposes
Trachea, punctures Injecting Bleomycin after Retaining according to Mouse Weight 2mg/kg in tracheal cartilages czermak space, is revolved the most parallel by animal immediately
Turning 2min, make medicinal liquid be evenly distributed in lung, then skin suture as far as possible, in placing cage after animal is naturally clear-headed, routine is raised
Support.The same method of NS group injects equal-volume normal saline.
(3) medication: after modeling second day, administration group gives embodiment 1, senior middle school's low dose group of 2,6, positive control
Group gives dexamethasone 2mg/kg/d, and blank group, model group all replace with the normal saline of same dose.Every day 1 time, even
Continuous 21 days.
(4) collection of specimens:
After being administered, the 21st day mouse orbit venous blood sampling separation serum is used for detecting TGF-β 1, then puts to death mice, opens
Breast separates double lung, takes right lung and is placed in 4% formalin fixing, and routine paraffin wax is cut into slices.Left lung homogenate, 3 000r/min from
After heart 10min, extract supernatant and be used for organizing MDA, HYP to detect (table 2,3).
Table 2 Plumula Nelumbinis extract causes the impact of pulmonary fibrosis mice serum TGF-β 1 to bleomycin
*p<0.05；* P < 0.01 compares with model group
From upper table result, in model group mice serum, TGF-β 1 is higher than Normal group, has pole significant difference
(P<0.01).In embodiment 1,2, dosage group compares with model group and has significant difference (P < 0.05), high dose group and model group
Relatively there is pole significant difference (P < 0.01)；Embodiment 6 is administered high dose group, middle dosage group relatively model group has pole significance poor
Different (P < 0.01), low dose group relatively model group has significant difference (P < 0.05), and presents a certain amount effect relationship.
Table 3 Plumula Nelumbinis extract causes the impact of HYP, MDA in pulmonary fibrosis mice lung tissue to bleomycin
*p<0.05；* P < 0.01 compares with model group
From upper table result, in model group mouse lung tissue, HYP, MDA are higher than Normal group, have pole significant difference
(P<0.01).Plumula Nelumbinis extract can reduce HYP content in mouse lung tissue, and embodiment 1,2 is administered high dose group, with model
Group compares and has significant difference (P < 0.05), embodiment 6 be administered high dose group relatively model group have pole significant difference (P <
0.01), middle dosage group relatively model group has significant difference (P < 0.05)；Plumula Nelumbinis extract on the impact of MDA from table,
In embodiment 1,2,6, dosage group compares with model group and has significant difference (P < 0.05), and high dose group compares tool with model group
There is pole significant difference (P < 0.01).
(5) pathological study
Alveolitis is divided into 4 grades by the pathological section utilizing HE to dye: without alveolitis (1 point)；Slight alveolitis (2 points): lung
Steep every because of cellular infiltration broadening, extent of disease is confined to less than the 20% of full lung；Moderate alveolitis (3 points): extent of disease accounts for entirely
The 20%～50% of lung；Severe alveolitis (4 points): be distributed in diffusivity, extent of disease ＞ 50%.Utilize Masson trichrome stain
Section interstitial pulmonary fibrosis is divided into 4 grades: without fibrosis (1 point)；Mild fibrosis (2 points): scope of getting involved is less than 20%；In
Degree fibrosis (3 points): the scope of getting involved accounts for the 20%～50% of full lung, alveolar structure is disorderly；Severe pulmonary fibrosis (4 points): get involved
Scope be more than 50%, fusion of pulmonary alveoli, pulmonary parenchyma structure disturbance.
The impact on pulmonary fibrosis mice lung morphology of table 4 Plumula Nelumbinis extract
Pulmonary fibrosis mice pathologic is affected by the Plumula Nelumbinis extract various dose gastric infusion of embodiment 6 preparation
(HE dyeing), is shown in Fig. 1, A in figure: Normal group B: model group C: positive controls D: high dose group E: middle dosage group F: low dose
Amount group.
Pulmonary fibrosis mice pathologic is affected by the Plumula Nelumbinis extract various dose gastric infusion of embodiment 6 preparation
(masson dyeing) is shown in Fig. 2, A in figure: Normal group B: model group C: positive controls D: high dose group E: middle dosage group F:
Low dose group.
Experiment proves: Plumula Nelumbinis extract can substantially suppress the HELF cell proliferation induced by TGF-β 1；Significantly reduce
The content of TGF-β 1 in the mice serum of bleomycin induction, the table of HYP, MDA in the mice lungs of suppression bleomycin induction
Reach, significantly improve bleomycin induced mice pulmonary fibrosis, pulmonary fibrosis treatment is had definite curative effect.
Claims (3)
1. Plumula Nelumbinis extract is in the application of preparation treatment pulmonary fibrosis medicine.
2. the preparation containing Plumula Nelumbinis extract is in the application of preparation treatment pulmonary fibrosis medicine.
Application the most according to claim 2, is characterized in that the dosage form of described preparation is granule, tablet, hard capsule, soft
Capsule, pill, oral liquid, effervescent tablet, dispersible tablet, drop pill or syrup.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108689932A (en) * | 2017-04-07 | 2018-10-23 | 中国医学科学院药物研究所 | The lotus nut alkali A and new alkali D of lotus seeds, preparation method and medical composition and its use |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101229232A (en) * | 2007-01-23 | 2008-07-30 | 北京琥珀光华医药科技开发有限公司 | Chinese traditional medicine preparation for curing pulmonary fibrosis |
| CN103768117A (en) * | 2014-01-28 | 2014-05-07 | 中国药科大学 | Application of Eclipta prostrate extract in preparation of anti-pulmonary fibrosis drugs |
-
2016
- 2016-07-18 CN CN201610569792.3A patent/CN106074719A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101229232A (en) * | 2007-01-23 | 2008-07-30 | 北京琥珀光华医药科技开发有限公司 | Chinese traditional medicine preparation for curing pulmonary fibrosis |
| CN103768117A (en) * | 2014-01-28 | 2014-05-07 | 中国药科大学 | Application of Eclipta prostrate extract in preparation of anti-pulmonary fibrosis drugs |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108689932A (en) * | 2017-04-07 | 2018-10-23 | 中国医学科学院药物研究所 | The lotus nut alkali A and new alkali D of lotus seeds, preparation method and medical composition and its use |
| CN108689932B (en) * | 2017-04-07 | 2021-01-12 | 中国医学科学院药物研究所 | Alternantherine A and neoliensinine D, preparation method thereof, pharmaceutical composition and application thereof |
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Application publication date: 20161109 |