Background technology
Bronchitis, pneumonia and asthma all belong to common respiratory tract disease, and their cardinal symptom has heating, headache, nasal obstruction, rhinorrhea, pharyngalgia, cough etc.The traditional Chinese medical science is thought, bronchitic pathogenesis is diseases caused by exogenous pathogenic factor and internal injury, and diseases caused by exogenous pathogenic factor are six climate exopathogens exopathogen invasion and attack lung systems, and internal injury is mainly caused by visceral dysfunction.Pneumonia is often because the heresy of wind heat or the heresy of wind and cold enter caused by inner heat-transformation.Asthma is because of exopathogen invasion and attack, the heresy of wind and cold, invasion and attack flesh table, internal resistance in lung, cold-evil's closing fur, lung qi loses respectful falling; Or because of in wind heat, lung-heat stops up Sheng, and clear respectful dereliction of duty or lung have intrinsic heat, and again by cold-evil is restrainted, heat must not be let out, caused by abnormal rising of lung-QI.In recent years, because industrial pollution causes environment for human survival Air Contamination more serious, cause respiratory tract disease prevalence to remain high and have the trend increased year by year, not only the populous of respiratory tract disease is suffered from by China, one of the World Health Organization's four large diseases chronic respiratory tract disease being classified as harm humans health.
Caulis Hederae Sinensis (Hedera nepalensis var. sinensis), it is Araliaceae Hedera plant, originate in Europe, Asia and north African, it can absorb the harmful substance in air by the Minute pores on blade, and it is converted into harmless sugared part and aminoacid, therefore, Caulis Hederae Sinensis effectively can resist the carcinogen in nicotine, can remove formaldehyde.Record according to China supplement to the Herbal: Caulis Hederae Sinensis have dispel the wind, dampness removing, suppressing the hyperactive liver, removing toxic substances effect, be usually used in treating rheumatic arthritis in the Chinese traditional treatment of China.Saponin is one of principle active component of Caulis Hederae Sinensis, is also studied maximum element of the first species in Hedera plant.Hederagenin is disaccharidase chain Hederagenin C(Hederacoside C), its molecular formula is C
59h
960
26, molecular weight 1221.Hederagenin has significant biological activity, as enhanced metabolism, immunomodulating, and the activity of cardiovascular, nerve and enzyme system and antiinflammatory, antibacterial, the effect such as antiviral, antitumor.The development of Chinese medicine separating and purifying technology in recent years, for Caulis Hederae Sinensis provides larger space in Chinese traditional treatment and Chinese patent medicine Application and preparation field.
Volatile oil is also referred to as quintessence oil, and as a kind of active component of plant, its composition is comparatively complicated, and effect is also different.The medical practice of ancient Chinese has found that volatile oil has wind dispelling, anthelmintic, eliminates the phlegm, stomach invigorating, relieving asthma, cough-relieving, the medical value such as antipyretic-antalgic and anti-inflammation.In recent years the pharmacological research of volatile oil is shown: volatile oil also has antiallergic, enzyme level, mutation, anticancer, many pharmacologically actives and the purposes such as antiviral and calm nervus centralis.
Caulis Hederae Sinensis is enriched in china natural resources, but not high to its utilization ratio at present, mainly as the green plants climbed.At present, the Chinese patent medicine for the treatment of respiratory tract disease generally adopts kinds of traditional Chinese medicines material to be used as medicine, containing more non-effective material.Numerous medical materials and component make the pharmacological action of relevant Chinese patent medicine be difficult to clearly, are difficult in addition work out Quality of Chinese Traditional Proprietary Medicine standard and quality control standard, are unfavorable for monitoring and the large-scale production of Chinese patent medicine product quality.In addition, although Caulis Hederae Sinensis extract in Europe clinical practice for many years, in the bronchitis etc. for the treatment of respiratory tract disease, also show good curative effect, but there is the higher problem of its untoward reaction rate simultaneously.One that carries out people such as S. Fazio in the evaluation of Caulis Hederae Sinensis extract safety and curative effect, the incidence rate of its untoward reaction reaches 2.7%, and this is mainly because the cilium that Caulis Hederae Sinensis blade exists can cause people's functional gastrointestinal disorder and skin allergy.
Summary of the invention
The object of the invention is to overcome above deficiency, a kind of medicine for the treatment of bronchitis, pneumonia and asthma is provided, it adopts the effective site extracted from Caulis Hederae Sinensis to be used as medicine: adopt Volatile Oil from Hedera nepalensis var. sinensis and Hederagenin to be mixed, make described medicine have the safety of more significant curative effect and Geng Gao.Another object of the present invention is, provides a kind of preparation method of described medicine, the Hederagenin obtained by alcoholic solution extraction, purification by macroporous resin, and not only active constituent content is high, and energy removal can cause the cilium of untoward reaction; In addition, add the Volatile Oil from Hedera nepalensis var. sinensis with antiinflammatory, antibacterial pharmacologically active, soft capsule or oral liquid can be made for actual therapeutic, the diseases such as bronchitis, pneumonia and asthma can be treated.
For achieving the above object, this invention takes following technical scheme.
A kind of medicine for the treatment of bronchitis, pneumonia and asthma, it is characterized in that, containing volatile oil and saponin two effective parts, described volatile oil is Volatile Oil from Hedera nepalensis var. sinensis, described saponin is Hederagenin, is by volume mixed mass ratio (mL:g) 1:40 ~ 100 by described Volatile Oil from Hedera nepalensis var. sinensis and Hederagenin.
For realizing above-mentioned second object, this invention takes following technical scheme.
Treat a preparation method for the medicine of bronchitis, pneumonia and asthma, comprise following steps: it is characterized in that:
(1) Volatile Oil from Hedera nepalensis var. sinensis is prepared
Take the stem and leaf of Caulis Hederae Sinensis, Caulis Hederae Sinensis stem and leaf and water is added by mass volume ratio 1:1 ~ 3 in extraction-rectification coupling apparatus, backflow, the light brown clear oil reservoir (volatile oil) occurred after collecting backflow also adds a small amount of natrium carbonicum calcinatum wherein and removes a little moisture, obtained Volatile Oil from Hedera nepalensis var. sinensis;
(2) Hederagenin is prepared
Take the stem and leaf of Caulis Hederae Sinensis, extract in still by mass volume ratio 1:3 ~ 10 of Caulis Hederae Sinensis stem and leaf and alcoholic solution by purity be 10 ~ 90% alcoholic solution reflux, extract, filter after reflux, extract, centrifugal, concentrating under reduced pressure, revolves steaming to extractum shape; With deionized water dissolving, cross macroporous resin column, use water and alcoholic solution eluting successively; By ethanol elution concentrating under reduced pressure (revolving steaming), 60 DEG C of vacuum dryings, weigh, obtained Hederagenin (extract);
(3) effective site component is prepared
Hederagenin obtained with step (2) for Volatile Oil from Hedera nepalensis var. sinensis obtained for step (1) is by volume mixed mass ratio (mL:g) 1:40 ~ 100, makes drug effective region component;
(4) medicine of preparation treatment bronchitis, pneumonia and asthma
1. effective site component mix homogeneously step (3) obtained, makes the soft capsule for the treatment of bronchitis, pneumonia and asthma;
2. effective site component mix homogeneously step (3) obtained, makes the oral liquid for the treatment of bronchitis, pneumonia and asthma.
Further, the macroporous resin column described in step (2) is HZ-816 macroporous resin column.
Further, the backflow described in step (2) at least carries out twice, and reflux extracting time is 1 ~ 4 hour for the first time, and second time reflux extracting time is 0.5 ~ 3 hour.
The Caulis Hederae Sinensis (Hedera nepalensis var. sinensis) that the present invention adopts, it is Araliaceae Hedera plant, have another name called soil drum rattan, bore sky wind, Radix Parthenocissi Heterophyllae, fall apart GUFENG, Radix Dendropanacis rattan, its stem and leaf are conventional Chinese medicine, there is effect of expelling wind and removing dampness, promoting blood circulation and detumescence, suppressing the hyperactive liver removing toxic substances, be usually used in the traditional Chinese medical science treatment rheumatic arthritis, lumbago, traumatic injury, hepatitis, dizziness, mouth eye snail tiltedly, epistaxis, corneal nebula, acute conjunctivitis, oedema due to nephritis, amenorrhea, swollen ulcer drug, urticaria, the disease such as eczema.
Good effect of the present invention is:
(1) provide a kind of medicine for the treatment of bronchitis, pneumonia and asthma, it adopts the effective site extracted from Caulis Hederae Sinensis: Volatile Oil from Hedera nepalensis var. sinensis and Hederagenin are mixed, and described medicine has positive effect to treatment bronchitis, pneumonia and asthma.
(2) present invention also offers a kind of preparation method of described medicine, the Hederagenin obtained by alcoholic solution extraction, purification by macroporous resin, not only active constituent content is high, and energy removal can cause the cilium of untoward reaction; In addition, add the Volatile Oil from Hedera nepalensis var. sinensis with antiinflammatory, antibacterial pharmacologically active, preparation method is simple, convenient, and reliable, can make Caulis Hederae Sinensis soft capsule or oral liquid for diseases such as actual therapeutic bronchitis, pneumonia and asthma.
(3) preparation method of the present invention is convenient to work out Quality of Chinese Traditional Proprietary Medicine standard and quality control standard aborning, is conducive to quality monitoring and the large-scale production of Chinese patent medicine product.In addition, energy removal can cause the cilium on the Caulis Hederae Sinensis blade of untoward reaction, can reduce and eliminate the untoward reaction after medication.
Detailed description of the invention
Below introduce a kind of detailed description of the invention for the treatment of the medicine of bronchitis, pneumonia and asthma and preparation method thereof of the present invention, provide 5 embodiments and 1 Application Example to explain the application in treatment bronchitis, pneumonia and asthma disease of preparation method and analyzing detecting method and the medicine prepared by checking in detail.But it may be noted that enforcement of the present invention is not limited to following embodiment.
embodiment 1
Treat a preparation method for the medicine of bronchitis, pneumonia and asthma, comprise following steps (see Fig. 1):
(1) Volatile Oil from Hedera nepalensis var. sinensis is prepared
Caulis Hederae Sinensis medical material (stem of Caulis Hederae Sinensis and leaf) is pulverized, then in extraction-rectification coupling apparatus, Caulis Hederae Sinensis medical material and the 20kg water of 10kg pulverizing is added by mass volume ratio 1:2, reflux, the light brown clear oil reservoir (volatile oil) occurred after collecting backflow also adds a small amount of natrium carbonicum calcinatum wherein and removes a little moisture (controlling the addition of natrium carbonicum calcinatum by the requirement of removing moisture), obtains Volatile Oil from Hedera nepalensis var. sinensis 2.8mL.
It should be noted that, the extraction-rectification coupling apparatus of employing is the device of applicant unit designed, designed, mainly comprises heater, extraction pot, rectifying column, condenser, oil-water separation extractor five parts.The entirety of device is based on 316L stainless steel.Heater wherein adopts electric heating steam generator, and heating power is 3000W, and quantity of steam controls at 0.2-0.5Mpa.Described heater is connected with the interlayer of sidewall with bottom described extraction pot by pipeline.Described rectifying column height is 1000mm, and internal diameter is 80mm, and the θ ring filler of φ=2.5mm is equipped with in its inside.The outer layer covers of described rectifying column has asbestos material and tinfoil to increase heat insulation effect.Described extraction pot height 700mm, internal diameter 300mm, volume is about 40L.Steam is heated by extraction pot interlayer.Described extraction pot inside is provided with the dividing plate of uniform pore openings, can realize rectification in rectification waterborne and water by controlling amount of water.Described condenser height is 450mm, internal diameter 20mm.Condenser external is cylindrical, and inside is equipped with pipe bundle condenser thus can be increased condensation area.The pipework condensation area of inner pipe bundle condenser is about 0.24m
2.The agent structure height 250mm of described oil-water separation extractor, internal diameter 25mm looks cup, by collecting volatile oil depending on the arm of cup bottom.Connected by a U-shaped pipe and rectifying column at the bottom welding looking cup lower-lying metal flange.By the valve below U-shaped pipe, can water be greater than to density and extract incomplete volatile oil and again extract.
(2) Hederagenin is prepared
Caulis Hederae Sinensis medical material (stem of Caulis Hederae Sinensis and leaf) is pulverized, then take Caulis Hederae Sinensis medical material that 10kg pulverizes and extract the alcoholic solution reflux, extract, twice with 60% in still, the mass volume ratio of Caulis Hederae Sinensis medical material and alcoholic solution is respectively 1:5(first time and refluxes solid-liquid ratio) and 1:3(to reflux for the second time solid-liquid ratio), first time backflow 3 hours, second time backflow 1.5 hours; Filter after reflux, extract, centrifugal, concentrating under reduced pressure, revolves and steams to extractum shape; With deionized water dissolving, cross HZ-816 macroporous resin column, then use water and ethanol elution successively; Finally ethanol elution is revolved steaming, 60 DEG C of vacuum dryings, weigh, obtained Hederagenin (extract) 157.0g.
3) effective site component is prepared
Hederagenin (extract) the by volume mass ratio 1:56(mL:g that the Volatile Oil from Hedera nepalensis var. sinensis obtained by step (1) and step (2) obtain) be mixed and made into drug effective region component
.
the analysis of the Hederagenin extract of embodiment 1 gained is detected
1, the Hederagenin extract 500mg that precision takes embodiment 1 step (2) gained adds 20mL methanol, 1mL hydrochloric acid heating hydrolysis; Hydrolysate adds water, with chloroform extraction twice, and each 20mL, separatory, merge extractive liquid, recycling design is to dry; Residue adds dissolve with methanol, standardize solution, obtained 5mg/mL need testing solution.
2, precision takes helexin reference substance (molecular formula is C
30h
48o
4) appropriate, with dissolve with methanol, be mixed with reference substance solution.
3, detection is analyzed
(1) draw need testing solution and reference substance solution respectively, water-bath volatilizes, and adds perchloric acid colour developing, and retinue reagent does blank, and scan in 190 ~ 600nm wave-length coverage, their chromatogram as depicted in figs. 1 and 2.The uv absorption spectra (see Fig. 2) of reference substance solution and uv absorption spectra (see Fig. 3) display of need testing solution: reference substance solution and need testing solution all have absorption maximum at 405nm place.Selected 405nm, for measuring wavelength, adopts ultraviolet spectrophotometry to detect: take absorbance as vertical coordinate, concentration is abscissa, drawing standard curve, measures total saponin content in the Hederagenin extract of embodiment 1 step (2) gained.
(2) need testing solution and reference substance solution is drawn respectively, (Inertsil ODS-SP C18 post under selected chromatographic condition; Mobile phase: acetonitrile-water (80:20, v/v); Column temperature: 30 DEG C; Flow velocity: 1mL/min; Determined wavelength: 210nm), injection liquid chromatography is analyzed.Take peak area as vertical coordinate, quality is abscissa, drawing standard curve, and measuring disaccharidase chain Hederagenin C(molecular formula in the Hederagenin extract of embodiment 1 step (2) gained is C
59h
960
26) content.The high-efficient liquid phase chromatogram of reference substance solution is see Fig. 4, and the high-efficient liquid phase chromatogram of need testing solution is see Fig. 5.
(3) testing result is analyzed
Analyze the result detected to show:
In the Hederagenin extract of embodiment 1 step (2) gained, Caulis Hederae Sinensis total saponin content is 81.63%.
In the Hederagenin extract of embodiment 1 step (2) gained, Hederagenin C(molecular formula is C
59h
960
26) content be 32.25%.
embodiment 2
Treat a preparation method for the medicine of bronchitis, pneumonia and asthma, comprise following steps:
(1) Volatile Oil from Hedera nepalensis var. sinensis is prepared
Caulis Hederae Sinensis medical material is pulverized, then in extraction-rectification coupling apparatus, Caulis Hederae Sinensis medical material and the 30kg water of 10kg pulverizing is added by mass volume ratio 1:3, reflux, the light brown clear oil reservoir (volatile oil) occurred after collecting backflow also adds a small amount of natrium carbonicum calcinatum wherein and removes a little moisture (controlling the addition of natrium carbonicum calcinatum by the requirement of removing moisture), obtains Volatile Oil from Hedera nepalensis var. sinensis 2.5mL.
(2) Hederagenin is prepared
Caulis Hederae Sinensis medical material (stem of Caulis Hederae Sinensis and leaf) is pulverized, then take Caulis Hederae Sinensis medical material that 10kg pulverizes and extract the alcoholic solution reflux, extract, twice with 10% in still, the mass volume ratio of Caulis Hederae Sinensis medical material and alcoholic solution is respectively 1:10(first time and refluxes solid-liquid ratio) and 1:5(to reflux for the second time solid-liquid ratio), first time backflow 4 hours, second time backflow 3 hours; Filter after reflux, extract, centrifugal, concentrating under reduced pressure, revolves and steams to extractum shape; With deionized water dissolving, cross HZ-816 macroporous resin column, then use water and ethanol elution successively; Finally ethanol elution is revolved steaming, 60 DEG C of vacuum dryings, weigh, obtained Hederagenin (extract) 167.5g.
embodiment 3
Treat a preparation method for the medicine of bronchitis, pneumonia and asthma, comprise following steps:
(1) Volatile Oil from Hedera nepalensis var. sinensis is prepared
Caulis Hederae Sinensis medical material is pulverized, then in extraction-rectification coupling apparatus, Caulis Hederae Sinensis medical material and the 10kg water of 10kg pulverizing is added by mass volume ratio 1:1, reflux, the light brown clear oil reservoir (volatile oil) occurred after collecting backflow also adds a small amount of natrium carbonicum calcinatum wherein and removes a little moisture, obtained Volatile Oil from Hedera nepalensis var. sinensis 2.9mL.
(2) Hederagenin is prepared
Caulis Hederae Sinensis medical material (stem of Caulis Hederae Sinensis and leaf) is pulverized, then take Caulis Hederae Sinensis medical material that 10kg pulverizes and extract the alcoholic solution reflux, extract, twice with 90% in still, the mass volume ratio of Caulis Hederae Sinensis medical material and alcoholic solution is respectively 1:5(first time and refluxes solid-liquid ratio) and 1:3(to reflux for the second time solid-liquid ratio), first time backflow 1 hour, second time backflow 0.5 hour; Filter after reflux, extract, centrifugal, concentrating under reduced pressure, revolves and steams to extractum shape; With deionized water dissolving, cross HZ-816 macroporous resin column, then use water and ethanol elution successively; Finally ethanol elution is revolved steaming, 60 DEG C of vacuum dryings, weigh, obtained Hederagenin (extract) 171.0g.
embodiment 4
The Volatile Oil from Hedera nepalensis var. sinensis 2.8mL that accurate extraction embodiment 1 step (1) is obtained, precision takes the obtained Hederagenin extract 157g of embodiment 1 step (2) and Cera Flava 40g, soybean phospholipid 10g, ethylparaben 1g is for subsequent use.
Described Cera Flava and soybean phospholipid are melted in 500mL PEG-4000; Add the obtained Hederagenin extract of the obtained Volatile Oil from Hedera nepalensis var. sinensis of embodiment 1 step (1), embodiment 1 step (2) and the abundant ground and mixed of ethylparaben again, make the medicinal liquid of modest viscosity, good fluidity.
Take water, gelatin and glycerol according to weight ratio 3:3:1 to pour in glue tank and be uniformly mixed at 60 DEG C of temperature, make gelatin solution; Then, institute's gelatine solution and described medicinal liquid are added in pellet press respectively, adjustment dose and rubber thickness, pelleting, dry, make the Volatile Oil from Hedera nepalensis var. sinensis of embodiment 1 extraction and the soft capsule of Hederagenin.
embodiment 5
The Volatile Oil from Hedera nepalensis var. sinensis 2.8mL that accurate extraction embodiment 1 step (1) is obtained, precision takes the obtained Hederagenin extract 157g of embodiment 1 step (2), mix homogeneously; Then add tween 80 100g, then add distilled water until medicinal liquid cumulative volume is 2L, stir, use Na
2cO
3regulate pH to 6.8, make Caulis Hederae Sinensis oral liquid.
Containing the volatile oil corresponding to 5g Caulis Hederae Sinensis medical material and saponin, i.e. 1.4 μ L Volatile Oil from Hedera nepalensis var. sinensis and 78.5mg Hederagenin extract in described Caulis Hederae Sinensis oral liquid every milliliter (ml).
application Example 1(checking the effect to treatment bronchitis, pneumonia and asthma)
This application embodiment is for the impact on the serum of the rat of the disease that suffers with chronic bronchitis, lung tissue SOD, CAT activity of the Caulis Hederae Sinensis oral liquid verifying embodiment 5 and prepare.
(1) the copying of rat model of chronic bronchitis
SD rat is placed in 11 ~ 17 DEG C of experimental situation adaptabilities to feed one week.Then modeling is respectively organized and adopt improvement fumigation to copy chronic bronchitis animal model with reference to " medical animal experiment method ".Modeling is respectively organized totally 32 rats and be placed in special 1m
3smoke-box in, light fumigation with wood shavings, sawdust, each 50g of Nicotiana tabacum L., every day 2 times, each 30min, continue 30 days.Normal group is then placed in normal smokeless environment and raises.
(2) grouping experiment
SD rat is divided into 5 groups at random, often organizes 10, male and female half and half.
1. Normal group: gavage normal saline 10ml/kg, every day 1 time.
2. model control group: gavage normal saline 10ml/kg, every day 1 time.
3. Caulis Hederae Sinensis extract (cct) high dose group: every day dosage 0.4ml/kg gavage.
4. Caulis Hederae Sinensis extract (cct) low dose group: every day dosage 0.2ml/kg, every day gavage 1 time.
5. GUILONG KECHUANNING group (positive control medication): every day dosage 1.0g/kg, every day gavage 1 time.
Described 5 groups of all continuous gavage normal saline or medicines 21 days the 2nd day after modeling terminates.
(3) experimental result
Table 1. Caulis Hederae Sinensis oral liquid is on the impact of SOD activity in chronic bronchitis rat blood serum, lung tissue and BALF
,
note:compare with Normal group:
▲ p< 0.01; Compare with model control group:
* p< 0.05,
* p< 0.01; Compare with cct group:
△ p< 0.01; Compare with GUILONG KECHUANNING group:
# p< 0.01.
Result shows: in model control group rat blood serum, lung tissue and BALF, the equal compared with normal matched group of SOD content obviously reduces (P < 0.01).Through medicine for treatment, treat the content of SOD in the serum of each group, lung tissue and BALF all higher than model control group (P < 0.05 or P < 0.01); In the serum of Caulis Hederae Sinensis extract (cct) high dose group, lung tissue and BALF, the content of SOD is all higher than GUILONG KECHUANNING group and Caulis Hederae Sinensis extract (cct) low dose group (P < 0.01), and has no notable difference (P > 0.05) between GUILONG KECHUANNING group and Caulis Hederae Sinensis extract (cct) low dose group.
Table 2. Caulis Hederae Sinensis oral liquid is on the impact of CAT activity in chronic bronchitis rat blood serum, lung tissue and BALF
,
note:compare with Normal group:
▲ p< 0.01; Compare with model control group:
* p< 0.05,
* p< 0.01; Compare with cct low dosage low dose of group:
△ p< 0.05,
△ △ p< 0.01; Compare with GUILONG KECHUANNING group:
# p< 0.05,
## p< 0.01.
Result shows: in model control group rat blood serum, lung tissue and BALF, the equal compared with normal matched group of the content of CAT obviously reduces (P < 0.01).Through medicine for treatment, treat the content of CAT in each group of serum, lung tissue and BALF all higher than model control group (P < 0.05 or P < 0.01); In cct high dose group serum, lung tissue and BALF, the content of CAT is all higher than GUILONG KECHUANNING group and cct low dose group (P < 0.05 or P < 0.01), and has no notable difference (P > 0.05) between GUILONG KECHUANNING group and cct low dose group.
Experimental result shows: Caulis Hederae Sinensis oral liquid prepared by the present invention has positive effect to treatment bronchitis, pneumonia and asthma.
illustrate:owing to being suitable for the administering mode taking gavage or injection in zoopery, soft capsule is comparatively large due to volume, tests and is difficult to swallow with rat, therefore, soft capsule is difficult to be filled into as oral liquid in rat body, so the present invention has mainly carried out animal experiment with Caulis Hederae Sinensis oral liquid.Because the composition of Caulis Hederae Sinensis soft capsule of the present invention is consistent with the composition of Caulis Hederae Sinensis oral liquid, thus, its curative effect also should be identical.