CN108030786A - Application of the corymbose hedyotis herb B prime in the medicine for preparing treatment Chronic Obstructive Pulmonary Disease - Google Patents
Application of the corymbose hedyotis herb B prime in the medicine for preparing treatment Chronic Obstructive Pulmonary Disease Download PDFInfo
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Abstract
The present invention relates to a kind of application of corymbose hedyotis herb B prime in the medicine for preparing treatment Chronic Obstructive Pulmonary Disease, belongs to biomedical sector, and invention is related to corymbose hedyotis herb B prime and is preparing the application in preventing Chronic Obstructive Pulmonary Disease medicine.The present invention has carried out animal model experiment using traditional Chinese medicine monomer corymbose hedyotis herb B prime; the results show; the lung function of Chronic Obstructive Pulmonary Disease experimental model caused by the corymbose hedyotis herb B prime exposes smoke from cigarette has preferable protective effect, has reverse effect to rat lung pathological change；The expression of proinflammatory factor IL 6 has inhibitory action in Chronic Obstructive Pulmonary Disease rat blood serum, BALF to cigarette induction, and the expression to the scorching factor IL 10 of suppression has facilitation, so as to mitigate airway inflammation.The corymbose hedyotis herb B prime of the present invention can be used as active constituents of medicine, and pharmaceutically acceptable carrier prepares the pharmaceutical composition of prevention Chronic Obstructive Pulmonary Disease.
Description
Technical field
The invention belongs to biomedical sector, is related to the new medicinal usage of the active ingredient corymbose hedyotis herb B prime of corymbose hedyotis herb, has
Body is related to corymbose hedyotis herb B prime and is preparing the application in preventing Chronic Obstructive Pulmonary Disease medicine.
Background technology
Chronic Obstructive Pulmonary Disease (Chronic Obstructive Pulmonary Disease, COPD) is a kind of slow
Property airway inflammation disease, lung's feature shows as not fully reversible flow limitation, often into carrying out sexual development.COPD clinical symptoms
Be mainly shown as chronic cough, expectoration, shortness of breath or expiratory dyspnea, pant with it is uncomfortable in chest, also occur that whole body with the progress of disease
Property inflammatory reaction etc., seriously affects the labour capacity and quality of life of patient.COPD incidence is high, and smoking is COPD most important
Hazards, for the incidence of Chinese more than 40 years old crowd up to 8.2%, foreign countries are 9-10%；The COPD death rates are high, in various diseases
The middle death rate occupies the 4th, city, the 3rd, rural area.
It there is no the effective means for the treatment of COPD at present, there are the following problems for COPD clinical treatments：Simple smoking cessation can not hinder
The only sustainable development of COPD chronic airway inflammations；Simple inhaled (ICS) antiphlogistic effects are bad, it is impossible to prevent or
Reverse the development process of COPD；Acted on using bronchodilator (β-AR activators) merely extremely limited；Therapeutic alliance (ICS/
β-AR activators), though can partly improve lung function, the death rate cannot be reduced.It can be seen from the above that can chronic airway inflammation obtain
It is to treat the key issue of COPD to control.
There is chronic inflammation in the air flue and pulmonary parenchyma of patient COPD, be particularly in Acute Exacerbation Period, airway inflammation
The class inflammatory mediator of the secretion such as high duration of response, neutrophil leucocyte, macrophage and lymphocyte, cell factor take part in
COPD pathogenic processes.Current research finds that in all multiple cytokines for participating in COPD inflammation, IL-6 and IL-10 have been main
The expression of the inflammatory factor of effect, IL-6 and IL-10 can represent the sick order of severity.IL-6 is in COPD acute attacks
Rise is detected in the induction of sputum and serum of phase patient, and IL-6 levels are gradually increasing with the increase of COPD series,
Reflect the severity of inflammation of COPD；IL-10 is found COPD lung tissues and air flue as a kind of conditioning agent of immune response
Infringement and the expression of IL-10, which decline, direct relation.
Based on case above, change horizontal IL-6 and IL-10 and the correlation of COPD under this research and inquirement drug effect
Help to be further understood that the specific mechanism of action of inflammatory factor, for COPD prevention and treatment provide clinical guidance with according to
According to, and then mitigate patient suffering, improve health, quality of making the life better.
Corymbose hedyotis herb is Rubiaceae (Rubiaceae) cerastium (Hedyotis) annual plant.Change in plants of Hedyotis
Studying point mainly includes：Pentacyclic triterpene, iridoids, flavonoids, Anthraquinones, lignans class, polysaccharide, sterol etc..Cyclenes
Ether terpene (Iridoid) derivative refers to the change that iridodial in plant kingdom (Iridoidia1) is formed by intramolecular aldol condensation
Compound, its architectural feature are generally to carry iridoid key with pentamethylene pyrans loop system, intramolecular.Of the present inventionization
Compound --- corymbose hedyotis herb B prime, is separated from Rubiaceae (Rubiaceae) cerastium (Hedyotis) plant corymbose hedyotis herb herb
A kind of iridoid of extraction, is the endemic element of corymbose hedyotis herb plant.Up to now, report concentrates on water both at home and abroad
The antitumor action research of line grass, there is not yet corymbose hedyotis herb and its contained active ingredient are applied to prevention Chronic Obstructive Pulmonary Disease
Correlative study report.
The content of the invention
The present invention provides a kind of application of corymbose hedyotis herb B prime in the medicine for preparing treatment Chronic Obstructive Pulmonary Disease, purpose
It is to provide the new medicinal usage of endemic element corymbose hedyotis herb B prime in Chinese medicine corymbose hedyotis herb.
Application of the corymbose hedyotis herb B prime of the present invention in the medicine for preparing treatment Chronic Obstructive Pulmonary Disease, the traditional Chinese medicine monomer
Component corymbose hedyotis herb B prime has the structure of formula (I),
The corymbose hedyotis herb B prime suppresses the infiltration of inflammatory cell, the expression of proinflammatory factor IL-6 and promotes suppression scorching
The expression of factor IL-10；
The lung function of the corymbose hedyotis herb B prime Protection model；
The experimental model is the Chronic Obstructive Pulmonary Disease experimental model caused by smoke from cigarette exposure；
It is made of a effective amount of corymbose hedyotis herb B prime and pharmaceutically acceptable auxiliary material, auxiliary material is disintegrant, and filler, lubricates
Agent, wetting agent, emulsifying agent, adhesive, the pharmaceutical preparation for tablet, capsule, pill, solution, injection, powder,
Suck preparation, spray, aerosol, syrup, oral solution formulation etc..
Extract containing corymbose hedyotis herb B prime is preparing the application in treating Chronic Obstructive Pulmonary Disease medicine.
The present invention combines conventional correlative study basis, and zoopery is carried out using above-mentioned traditional Chinese medicine monomer corymbose hedyotis herb B prime.It is long
Phase smoking is most common mankind COPD pathogenic factors, therefore uses cigarette induction simulation rat COPD model research corymbose hedyotis herb B prime
Mitigation to the COPD of cigarette induction.COPD rat models caused by being exposed using smoke from cigarette, and done with corymbose hedyotis herb B prime
Pre- animal, experimental result are shown：1st, gavage give 6,12, the corymbose hedyotis herb B prime of 24mg/kg smoke from cigarette is exposed caused by COPD
The lung function of rat has protective effect；2nd, the inflammation of COPD rat models caused by corymbose hedyotis herb B prime in vivo exposes smoke from cigarette
The infiltration of cell, the expression of proinflammatory cytokine have inhibitory action；3rd, the above-mentioned effect of corymbose hedyotis herb B prime is with suppressing mice serum
Expression to proinflammatory factor IL-6 in BALF is related to the expression for pressing down scorching factor IL-10 is promoted.
Embodiment
Embodiment 1：The preparation method of compound corymbose hedyotis herb B prime involved in the present invention
Dry corymbose hedyotis herb herb 9.0kg is taken, adds 90% ethanol (v/v) refluxing extraction at room temperature, when reflux 2 is small every time,
Reflux 3 times, vacuum-concentrcted obtains alcohol-extracted extract 920.0g, and medicinal extract is suspended in suitable quantity of water, adds the water saturation of 1.5 times of volumes
Extracting n-butyl alcohol 3 times, water layer discarded.N-butyl alcohol extract (91.0g) carries out silica gel column chromatography (chloroform-methanol 15:1→3:1),
Obtain Fr.A-I.Fr.E6 passes through silica gel column chromatography (1.CHP-20P, MeOH/H again2O 4:1；2.SiO2,AcOEt/i-PrOH 15:
1→6:1):Fr.E6.1-E6.8.Fr.E6.3 carries out silica gel column chromatography (Sephadex LH-20；MeOH/H2O 2:3→1:1),
Carry out preparing thin-layer chromatography (SiO again2；CHCl3/i-PrOH 4:1) corymbose hedyotis herb B prime (14mg), is obtained.
White amorphous powder, molecular formula：C24H28O12, molecular weight：508.47, boiling point：763.9±60.0℃
(760Torr), density：1.54±0.1g/cm3(20 DEG C, 760Torr), pKa：8.14±0.15.Corymbose hedyotis herb B prime1HNMR
(300MHz,DMSO-d6) the following δ of data:
5.25 (1H, d, J=7.5Hz), 7.49 (1H, br.s), 2.14 (1H, dd, J=7.8,16.5Hz), 2.87 (1H,
Dd, J=7.8,16.5Hz), 5.91 (1H, br.s), 2.83 (1H, br.t, J=7.5Hz), 5.08 (1H, br.d, J=
14.0Hz), 4.93 (1H, br.d, J=14.0Hz), 3.69 (3H, s), 4.77 (1H, d, J=7.8Hz), 3.29 (1H, t, J=
8.6Hz), 3.47 (1H, t, J=8.6Hz), 3.40 (1H, t, J=8.6Hz), 3.38-3.36 (1H, m), 3.82 (1H, dd, J=
2.5,11.9Hz), 7.94 (2H, d, J=8.8Hz), 6.93 (2H, d, J=8.8Hz).
13CNMR (75MHz, DMSO-d6)：97.9 (C-1), 152.5 (C-3), 112.1 (C-4), 35.9 (C-5), 39.5
(C-6), 130.2 (C-7), 139.7 (C-8), 47.3 (C-9), 63.2 (C-10), 168.0 (C-11), 100.5 (C-1'), 74.5
(C-2'), 77.6 (C-3'), 71.1 (C-4'), 77.8 (C-5'), 62.6 (C-6'), 122.1 (C-1 "), 132.6 (C-2 ",
6 "), 116.1 (3 ", 5 "), 163.0 (C-4 "), 166.7 (C-7 ").
Embodiment 2:The preparation of compound corymbose hedyotis herb B prime tablet involved in the present invention
5 grams of corymbose hedyotis herb B primes are taken, add starch 30g, are uniformly mixed, 70% ethanol of penetrating is wetting agent, and softwood is made；Cross
20 mesh sieve nets, obtain wet granular；60 DEG C of dryings, are stirred one time per 30min, and moisture is controlled 1%~3%.Add dolomol
End, mixes, is pressed into 1000.
Embodiment 3:The preparation of compound corymbose hedyotis herb B prime capsule involved in the present invention
Supplementary material is crossed to No. five sieves, in favor of mixing completely, uniformly, corymbose hedyotis herb B prime 5g, starch 28g is weighed, mixes
Uniformly, encapsulated 1000.
Embodiment 4:The reverse that corymbose hedyotis herb B prime changes Chronic Obstructive Pulmonary Disease (COPD) rat model lung pathologies
Effect
Lipopolysaccharides is injected with tracheae and fumigation joint modeling method prepares COPD rat models：1st, 14 day rat abdominal cavity note
Yellow Jackets (1%, 40mg/kg) are penetrated, make anesthesia, fixed, head low level, exposure glottis, No. 18 venous catheter needles of quick insertion
Tracheae, extracts needle core, then that rat is straight with injection 0.2mL lipopolysaccharides normal saline solution (200 μ g/ μ L) in syringe 1s
Vertical left rotation and right rotation, makes lipopolysaccharides be uniformly distributed two lungs.Rat packet is inserted and makes closed make by oneself by the 2nd~28 day (except the 14th day)
In moulding box, in the daily morning, give rat cigarette sootiness 30m i n, every time 4 cigarette.
After modeling success, 50 rats are randomly divided into 5 groups:Normal group, model group and corymbose hedyotis herb B prime are basic, normal, high
Dosage group (6,12,24mg/kg).Gavage gives pure water (10mL/kg), corymbose hedyotis herb B prime respectively for Normal group, model group
Gavage awards corymbose hedyotis herb B prime, successive administration 14 days to each dosage group respectively.Hematoxylin-eosin (HE) dyeing observation pathologic
Learn and change.
As a result：Model group rats broncho-pulmonary tissue has a pathological change of Chronic Obstructive Pulmonary Disease, on bronchus cilium
Skin portion comes off, cilium adhesion lodging, denaturation；Bronchial tube intracavitary has moderate exudate；Tracheal mucosa lower floor, muscle layer are visible big
Measure acidophic cell, lymphocytic infiltration.Adhesion that the middle and high dosage group bronchus cilium of corymbose hedyotis herb B prime is slight lodging, denaturation, branch
Tracheal smooth muscle thickness slightly increases；Tracheal mucosa lower floor, the visible a small amount of acidophic cell of muscle layer；Lymphocyte and a small amount of slurry are thin
Born of the same parents infiltrate.
Embodiment 5:Influence of the corymbose hedyotis herb B prime to Chronic Obstructive Pulmonary Disease (COPD) rat model lung function
Male Wister rat, 120~150g of weight.Test the 1st day, after the 14th day uses chloral hydrate anesthesia rat,
Surgical exposure tracheae, instills LPS (1g/L, 200 μ L), and rat is placed in smoke-box by next day, puts sootiness, one time a day, every time
30min, totally 28 days.After modeling success, rat is randomly divided into 5 groups:Normal group, model group and corymbose hedyotis herb B prime are basic, normal, high
Dosage group (6,12,24mg/kg).Gavage gives pure water (10mL/kg), corymbose hedyotis herb B prime respectively for Normal group, model group
Gavage awards corymbose hedyotis herb B prime, successive administration 14 days to each dosage group respectively.
Lung function tests：Rat anesthesia, cuts skin of neck, blunt separation subcutaneous tissue exposure tracheae, in cartilagines tracheales
Between go in ring and cut off a small notch, insertion trachea cannula simultaneously tightens, and a low level of lying on the back is placed in toy pulmonary function test apparatus obturator
Product is traced in case.Trachea cannula one end is connected with animal respirator.Forced vital capacity is detected after tracing one section of normal respiration
(FVC), 0.3s forced expiratory volumes (FEV0.3), FEV0.3/FVC, forced expiration peak velocity (PEF).
As a result：Compared with Normal group, model group rats lung function parameter FVC, FEV0.3, FEV0.3/FVC, PEF is equal
Significantly reduce, difference is statistically significant (P ＜ 0.05 or P ＜ 0.01), illustrates modeling success.Compared with model group, waterline
Careless basic, normal, high dosage group lung function parameter FVC, FEV0.3, FEV0.3/FVC, PEF of B prime is significantly raised, and difference has system
Meter learns meaning (P ＜ 0.05 or P ＜ 0.01), the results are shown in Table 1.
Influence (n=10, X ± SD) of the 1 corymbose hedyotis herb B prime of table to COPD rat model lung function
△Compared with Normal group, P<0.05；△△Compared with Normal group, P<0.01
* compared with Normal group, P<0.05；* is compared with Normal group, P<0.01
Conclusion：Corymbose hedyotis herb B prime can improve the lung function of Chronic Obstructive Pulmonary Disease (COPD) rat model.
Embodiment 6:Corymbose hedyotis herb B prime is observed to proinflammatory factor in Chronic Obstructive Pulmonary Disease (COPD) rat model serum
IL-6 and the influence of the scorching factor IL-10 expression of suppression
Modeling method and medication are the same as embodiment 4.
After administration, abdominal aortic blood, 3000r/min centrifugation 10min, Aspirate supernatant is to be checked, and part serum is placed in -20
It is DEG C to be measured.Enzyme-linked immunosorbent assay (ELISA) detection serum interleukins is horizontal；Interleukins (IL-6, IL-10) is examined
Test agent box provides (lot number 2012011202,2011120407) by R＆D companies of the U.S..As a result：Model group IL-6 expressions
More normally organize significantly raised (P<0.01)；The basic, normal, high dosage group IL-6 expressions of corymbose hedyotis herb B prime are significantly reduced compared with model group
(P<0.05).Model group IL-10 expressions more normally organize obvious reduction (P<0.01)；The basic, normal, high dosage group of corymbose hedyotis herb B prime
IL-10 expressions significantly raise (P compared with model group<0.05).
The influence (n=10, X ± SD) that 2 corymbose hedyotis herb B prime of table expresses IL-6 in COPD rat model serum and IL-10
△Compared with Normal group, P<0.05；△△Compared with Normal group, P<0.01
*Compared with Normal group, P<0.05
Conclusion：The expression of proinflammatory factor IL-6 has suppression to make in the COPD rat blood serums that corymbose hedyotis herb B prime induces cigarette
With, and the expression to the scorching factor IL-10 of suppression has facilitation.
Embodiment 7:Corymbose hedyotis herb B prime is observed to Chronic Obstructive Pulmonary Disease (COPD) rat model bronchoalveolar lavage
The influence of proinflammatory factor IL-6 and the scorching factor IL-10 expression of suppression in liquid (BALF)
Modeling method and medication are the same as embodiment 4.
Rat anesthesia, fixation of lying on the back, puts to death, opens thoracic cavity, remove heart, rinses lung 1-2 times with ice-cold NS, blots.With dynamic
Arteries and veins pincers clamp right lung door, separate pars cervicalis tracheae, open T row notch in nearly tracheae crotch, be intubated to left bronchus lower end crotch,
At sutures ligation trachea cannula, at ligation two.Drawn with syringe and be preheated to (37 DEG C) or the physiological saline of room temperature
2ml, intrapulmonary is slowly injected into by conduit with less pressure by brine, it is seen that left lung gradually becomes bulge, pale, immediately slowly
Pumpback irrigating solution, then gained liquid is slowly injected back into intrapulmonary, so pumping 2 times repeatedly, obtain BALF liquid.
The horizontal of enzyme-linked immunosorbent assay (ELISA) detection serum interleukins；Interleukins (IL-6, IL-10)
Detection kit provides (lot number 2012011202,2011120407) by R＆D companies of the U.S..
As a result：Model group IL-6 expressions more normally organize significantly raised (P<0.01)；Basic, normal, high dose of corymbose hedyotis herb B prime
Amount group IL-6 expressions significantly reduce (P compared with model group<0.05).Model group IL-10 expressions more normally organize obvious reduction
(P<0.01)；The basic, normal, high dosage group IL-10 expressions of corymbose hedyotis herb B prime significantly raise (P compared with model group<0.05).
Conclusion：The expression of proinflammatory factor IL-6 has suppression to make in the COPD BALF of Rats that corymbose hedyotis herb B prime induces cigarette
With, and the expression to the scorching factor IL-10 of suppression has facilitation.
Claims (8)
1. a kind of application of corymbose hedyotis herb B prime in the medicine for preparing treatment Chronic Obstructive Pulmonary Disease, the corymbose hedyotis herb B prime
With following chemical constitution：
2. the application as described in claim 1, it is characterised in that：The corymbose hedyotis herb B prime suppresses the infiltration of inflammatory cell, promotees
The expression of scorching factor IL-6 and the expression for promoting the scorching factor IL-10 of suppression.
3. the application as described in claim 2, it is characterised in that：The corymbose hedyotis herb B prime has the work(of Protection model lung
Energy.
4. the application as described in claim 3, it is characterised in that：The experimental model is chronic caused by smoke from cigarette exposure
Obstructive disease of lung experimental model.
A kind of 5. pharmaceutical preparation for treating Chronic Obstructive Pulmonary Disease, it is characterised in that：By a effective amount of corymbose hedyotis herb B prime and medicine
Acceptable auxiliary material composition on.
A kind of 6. pharmaceutical preparation for treating Chronic Obstructive Pulmonary Disease according to claim 5, it is characterised in that：It is described auxiliary
Expect for disintegrant, filler, lubricant, wetting agent, emulsifying agent, adhesive.
A kind of 7. pharmaceutical preparation for treating Chronic Obstructive Pulmonary Disease according to claim 5, it is characterised in that：Described
Pharmaceutical preparation for tablet, capsule, pill, solution, injection, powder, suction preparation, spray, aerosol, syrup,
Oral solution formulation.
8. the extract containing corymbose hedyotis herb B prime is preparing the application in treating Chronic Obstructive Pulmonary Disease medicine.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113425714A (en) * | 2021-08-04 | 2021-09-24 | 华南师范大学 | Application of indoleacetic acid in preparation of medicine for preventing and treating chronic obstructive pulmonary disease |
-
2017
- 2017-11-30 CN CN201711247235.0A patent/CN108030786A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113425714A (en) * | 2021-08-04 | 2021-09-24 | 华南师范大学 | Application of indoleacetic acid in preparation of medicine for preventing and treating chronic obstructive pulmonary disease |
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Application publication date: 20180515 |