CN102552242A

CN102552242A - Application of nobiletin to preparation of medicament for treating allelgic asthma

Info

Publication number: CN102552242A
Application number: CN2012100156133A
Authority: CN
Inventors: 李康
Original assignee: Individual
Current assignee: Individual
Priority date: 2012-01-18
Filing date: 2012-01-18
Publication date: 2012-07-11

Abstract

The invention discloses an application of nobiletin to preparation of a medicament for treating allelgic asthma. According to the invention, the nobiletin has a histamine antagonism effect, is an H1 receptor blocker, has a remarkable suppressing effect on a tracheal smooth muscle contraction reaction caused by His, has a smaller using amount, being 1/4.3 that of a theophylline sustained-release tablet serving as a positive control medicament for reaching the same suppressing rate, is basically free from toxic and side effects, and is an allergic asthma treating medicament with a development prospect.

Description

The application of Nobiletin in preparation treatment allergic asthma medicine

Technical field

The present invention relates to the new purposes of Nobiletin, be specifically related to the application of Nobiletin in preparation treatment allergic asthma medicine.

Background technology

Nobiletin is disclosed chemical compound, and its structure is:

。This chemical compound belongs to flavone compound, is clear crystal.Nobiletin derives from Rutaceae river Fructus Citri tangerinae Citrus nobilis Lour. peel, Citrus aurantium Linn. C.aurantium L. peel, leaf and the stem of Citrus C.reticulata Blanco.Nobiletin has that anti-hemagglutination, antithrombotic form, anticancer, antifungal, antiinflammatory, antiallergic, anticholinergic and antiepileptic action, also can do carbohydrate metabolism promoter.

The application of CN102048726A Nobiletin discloses Nobiletin and has had the medicine of haemostatic effect or the application in the health product in preparation, and points out that Nobiletin has anastalsis preferably, also has the effect of easing pain and diminishing inflammation.

The method of CN101257911A control adipose cell fat generation discloses Nobiletin and has had the effect of controlling fat generation in the adipose cell.

The application of flavone compound in the preparation anti-angiogenic drugs discloses flavone compound in the Pericarpium Citri Reticulatae in the CN101947215A Pericarpium Citri Reticulatae; Like the application in the preparation anti-angiogenic drugs such as Sinensetin, Tangeretin or Nobiletin, and can treat excessive angiogenesis diseases associated.

Wang Qiaoling; Jia Shaohua etc.; Point out that in Nobiletin antitumaous effect and Study and advance on mechanism Nobiletin is a kind of polymethoxyflavone compounds, except having effects such as antiinflammatory, antioxidation, antiviral, points out that also Nobiletin has extremely strong active anticancer.

At present, do not find the report of the application of Nobiletin in the allergic asthma medicine as yet.

Asthma be a kind of be that eosinophilic granulocyte and mast cells infiltration are the cellular immunity disease of main pathological characters with the airway inflammation cell.And histamine is one of main medium of allergic asthma outbreak; Histamine H1-receptor quantity increases during asthma attack; Histamine makes bronchospasm through stimulating the H1 receptor; Function is hyperfunction relatively, thus suppress histamine release or blocking histamine and receptor to combine be one of effective means of clinical prevention allergic asthma.

Summary of the invention

The object of the present invention is to provide the application of Nobiletin in preparation treatment allergic asthma medicine.

The technical scheme that the present invention takes is:

The application of Nobiletin in preparation treatment allergic asthma medicine.

The invention has the beneficial effects as follows:

The present invention proves that Nobiletin has the effect of antagonism histamine; Be the H1 receptor blocking agent, the tracheal smooth muscle contractile response due to the His is had obvious inhibitory action, and compare with positive control medicine Theo-Dur; Consumption when reaching identical suppression ratio is less than the consumption of Theo-Dur; Being about Theo-Dur consumption 1/4.3, and having no side effect basically, is a kind of medicine that the treatment allergic asthma of DEVELOPMENT PROSPECT is arranged.

Description of drawings

The inhibitory action that Fig. 1 shrinks for the isolated helical strips of guinea that the Nobiletin group is brought out His;

Fig. 2 is that the consumption and the suppression ratio of Nobiletin and theophylline compares.

The specific embodiment

The inhibitory action that the isolated helical strips of guinea of His being brought out below in conjunction with concrete description of test Nobiletin is shunk.

1. medicine and reagent

Theo-Dur (Guangzhou Medtech Xinghua Pharmaceutical Co., Ltd., batch number: 20101008, specification: 100mg/ sheet, dissolve with ethanol); Histamine phosphate (His, Guangzhou Qi Yun Bioisystech Co., Ltd, dissolved in distilled water); Krebs solution (Krebs-Henseleit, K-H): NaCl 7.5g, KCl 0.35g, NaH ₂PO4 0.1 g, NaHCO ₃1.0 g, MgCl ₂0.05 g, CaCl ₂0.24 g (above reagent is Guangzhou Chemical Reagent Factory), glucose 1 g (Tianjin Da Mao chemical reagent factory) are earlier with CaCl ₂Complete with dissolved in distilled water, add surplus materials dissolving again, be transferred in the volumetric flask, be settled to 1000 ml with distilled water, more than each reagent be analytical pure.

2. Nobiletin preparation

The 2kg Pericarpium Citri Reticulatae is pulverized the back use 60% ethanol extraction, concentrating under reduced pressure, the concentrated solution that obtains are successively with the petroleum ether of the long-pending amount of monoploid, the chloroform extraction of the long-pending amount of monoploid; Extract respectively three times, obtain the chloroform extraction part, adopt petroleum ether-ethyl acetate system silicagel column eluting; TLC examines knowledge, and (both ratios are the eluting part of 6:1～3:1), upper prop cyclohexane extraction-acetone eluting again to merge petroleum ether-ethyl acetate; (both ratios are the eluting part of 8:1～6:1) to merge cyclohexane extraction-acetone; (both ratios are the eluting of 10:1～8:1) to upper prop dichloromethane-acetone, and eluent uses volume ratio to obtain pure article as the dehydrated alcohol of 2:1 and the mixed liquor recrystallization of water, through IR again; Methods such as 1H-NMR are confirmed structure, and are consistent with the Nobiletin structure.

3. animal

Cavia porcellus, body weight 250～300 g, male and female have concurrently, and Traditional Chinese Medicine University Of Guangzhou learns the animal feeding center credit number is provided: scxk (Guangdong) 2008-0020.

4. instrument

The muscle tone transducer: the JZ100 type, available from the industrial scientific & trading Co., Ltd. of the new boat in Beijing; Medlab (V6.0) bio signal acquisition processing system is available from Meiyi Science & Technology Co., Ltd., Nanjing.

5. sample preparations

The tap the head back that causes death of Cavia porcellus is taken out trachea between larynx and the knuckle rapidly, immerses in the krebs solution (K-H) of logical oxygen, softly removes around the trachea behind the loose connective tissue and fat; Be cut into wide about 3 mm, the trachea spiral bar of long 20 mm is put into 37 ± 0.5 ℃ of thermostatic baths that contain 17.5 ml krebs solutions as BIAO and BEN; Last termination muscular tension transducer gives trachea spiral bar BIAO and BEN rest tension 1.0g, continues to pass to oxygen; The record muscular tension, per 20 min change krebs solution 1 time, balance 60 min.

6. experiment is divided into groups

Experiment divides three groups, every group of two 5 BIAO and BEN, and the A group is the blank group, and the B group is the Nobiletin group, and the C group is the Theo-Dur group.

7. experimental technique

After the BIAO and BEN balance, adding histamine phosphate (His) to its concentration in the thermostatic bath krebs solution is 1.0 * 10 ^-3G/L, the stable back of BIAO and BEN tension force rising (tension force≤± 0.1g), record tension force at this moment.

Every group adds Nobiletin, theophylline and the ethanol of variable concentrations respectively with accumulation technology, respectively as experimental group, positive control Theo-Dur group and blank group.The Nobiletin group adds the Nobiletin of dissolve with ethanol, and the Theo-Dur group adds the Theo-Dur of dissolve with ethanol, and the blank group adds ethanol.

The interval measure method that provides with Medlab (V6.0) bio signal acquisition processing system software is measured the mean tension of the 1st min after the dosing, and calculates suppression ratio according to the mean tension value.The suppression ratio computing formula is following: suppression ratio (%)=(to mean tension after mean tension-administration behind the histamine phosphate)/(to mean tension-rest tension behind the histamine phosphate) * 100%.

8. statistical analysis

The result is so that (the t check is relatively adopted in ± s, n=5) expression between group.

9. interpretation of result

The result that influences that each medicine shrinks GPT spiral bar due to the histamine sees table 1, Nobiletin group, Theo-Dur group and blank group comparing difference significance (P 0.05).The inhibitory action figure that the isolated helical strips of guinea that the Nobiletin group is brought out His is shunk sees Fig. 1, can be known all that by Fig. 1 and table 1 Nobiletin is 6.02 * 10 in concentration ^-3～1.80 * 10 ^-2All the isolated tracheal spasm due to the His is had inhibitory action in the scope of g/L, and inhibitory action is concentration dependent.Nobiletin concentration is 6.02 * 10 ^-3The time, suppression ratio is-1.87%, the effect of suppression ratio is variant but not significantly (P=0.15＞0.01).Nobiletin concentration is 1.80 * 10 ^-2During g/L, suppression ratio is 95.83%, and there were significant differences for inhibitory action (P＜0.01).

The consumption and the suppression ratio of Nobiletin and Theo-Dur (abbreviation theophylline) are relatively seen Fig. 2.Can know by Fig. 2 and table 1; Nobiletin group and Theo-Dur group (positive controls) relatively, when identical when (about 50%), the consumption of Nobiletin is less than the consumption of theophylline to the isolated tracheal spasm suppression ratio due to the His; The theophylline suppression ratio reaches at 50% o'clock, and drug level is about 5.120 * 10 ^-2G/L; The Nobiletin suppression ratio reaches at 50% o'clock, and drug level is about 1.20 * 10 ^-2, be about theophylline consumption 1/4.3.

The influence that each medicine of table 1 shrinks GPT spiral bar due to the histamine

Nobiletin has obvious inhibitory action to the tracheal smooth muscle contractile response due to the His, because histamine is one of main medium of allergic asthma outbreak, histamine H1-receptor quantity increases during asthma attack; Function is hyperfunction relatively; So suppress histamine release or blocking histamine and receptor to combine be one of effective means of clinical prevention allergic asthma, and Nobiletin has the effect of antagonism histamine, is the H1 receptor blocking agent; So Nobiletin has therapeutical effect to allergic asthma; And compare with positive control medicine theophylline, less than theophylline, be about Theo-Dur consumption 1/4.3 on the consumption when reaching identical suppression ratio; And having no side effect basically, is a kind of medicine that the treatment allergic asthma of DEVELOPMENT PROSPECT is arranged.

Claims

1. the application of Nobiletin in preparation treatment allergic asthma medicine.