CN1513518A - Medicine for treating acute chronic bronchitis and its preparation method - Google Patents
Medicine for treating acute chronic bronchitis and its preparation method Download PDFInfo
- Publication number
- CN1513518A CN1513518A CNA031356303A CN03135630A CN1513518A CN 1513518 A CN1513518 A CN 1513518A CN A031356303 A CNA031356303 A CN A031356303A CN 03135630 A CN03135630 A CN 03135630A CN 1513518 A CN1513518 A CN 1513518A
- Authority
- CN
- China
- Prior art keywords
- medicine
- ethanol
- composition
- volatile oil
- chronic bronchitis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A Chinese medicine for treating acute or chronic bronchitis is prepared from azalea and additive through distilling azalea to obtain its volatile oil, extracting the distilled residue by content 70-90 % alcohol to obtain active components, and proportionally mixing the volatile oil, active components and additive. Its advantages are high curative effect and high safety.
Description
Technical field
The present invention relates to be a kind of be the medicine and preparation method thereof of the treatment acute/chronic bronchitis of effective medicinal ingredient with the natural drug raw extract.
Background technology
Acute/chronic bronchitis is commonly encountered diseases, the frequently-occurring disease in the respiratory tract system disease.Mainly show as dyspnea, excessive phlegm, asthma clinically.Present medicine mainly is bronchial spasmolytic agent, hormone, antibiotics and spray etc., though this class medicine can make patient's symptom at that time alleviate to some extent, instant effect recurs also fast often.
The relevant report that can be used for treating bronchitic types of drugs in Chinese medicine is more, as Folium Rhododendri Daurici, Rhododendron, Folium et Cacumen Rhododendri Mariae, Folium Rhododendri Micranthi etc.But remove flavone compounds such as containing the Quercetin that can have the cough-relieving composition, Quercitroside, hyperin in these medicine materials, and have outside the scopoletin, kaempferol of the astragaloside of expectorant function and the composition of relievining asthma, maximum problem is more or less all also to contain poisonous one-tenth to divide andromedotoxin.Andromedotoxin is a kind of violent heart-neural malicious composition, and poisoning manifestations is faint slow for violent vomiting, shock, heart beating, and tachypnea is spastic breathing.Experiment showed, the LD of mice Kou Fu andromedotoxin through institute of Materia Medica,Chinese Academy of Medical Sciences
50Be the 4.5mg/ kilogram, intravenous injection LD
50Be the 0.345mg/ kilogram, big more than the toxicity of cyanide.For example, experimental result aspect subacute toxicity shows, even claim the not Folium Rhododendri Daurici of Han You andromedotoxin in the report, in the time of the 40-80 that is equivalent to clinical consumption times, the hepatic and renal function of rat and pathologic finding and body weight are still had certain influence, prove that wherein still containing is micro-De andromedotoxin at least.This just gives medication, and particularly the patient to long-term prescription brings unsafe factor potential or at a specified future date.In addition, in the present data of grasping,, also only have to adopt and extract its volatile oil, and can't adopt the report of its flavone component as effective medicinal ingredient to medicinal raw materials such as Folium Rhododendri Daurici, Rhododendrons; And medicinal raw materials such as Folium Rhododendri Micranthi, Folium et Cacumen Rhododendri Mariae are also only had adopting water extract to use as effective medicinal ingredient, and do not see the report that has its volatile oil utilization.
Summary of the invention
According to above-mentioned situation, the present invention will provide a kind of medicine and preparation method thereof of treatment acute/chronic bronchitis of the treatment that contains new effective medicinal ingredient.Through experiment and contrast, the prime advantage of this medicine can be wherein not contain deleterious andromedotoxin composition, and not only safety is higher, and curative effect is also even more ideal.
The present invention treats the medicine of acute/chronic bronchitis, is that the extract with Liangshan Mountain Cuculus polioephalus is effective medicinal ingredient, forms with acceptable complementary adding ingredient mixed together in the medicine.Here the extract of said Liangshan Mountain Cuculus polioephalus, the volatile oil component that is contained in the Liangshan Mountain Cuculus polioephalus medicine material that can comprise ins all sorts of ways obtains, and in a usual manner by its decocting liquid at least a in the resulting ethanol-soluble extractives composition after the ethanol of higher concentration carries out purification process again.Said this medicine for treatment thing among the present invention, can comprise oral formulations form medicine, also comprise the multiple pharmaceutical dosage forms such as preparation of the injection form for preparing by above-mentioned effective medicinal ingredient with conventional method as solid such as oral liquid commonly used, dissolved granule, tablet, capsule, drop pill or liquid form.
Liangshan Mountain Cuculus polioephalus is the plant of a kind of Ericaceae Rhododendron.Show with comparative test result after testing, with different extracting method, can obtain having different effective medicinal ingredients respectively, wherein comprise above-mentioned various effective medicinal ingredient, as have the flavonoid component such as Quercetin, Quercitroside, hyperin of cough-relieving, the astragaloside composition with expectorant function, and have compositions such as the scopoletin of relievining asthma, kaempferol, and show that through repeatedly comparative test result its most outstanding advantage is not contain deleterious andromedotoxin composition.
During above-mentioned medicine is formed, though said effective medicinal ingredient can be adopted as the volatile oil component that is contained in the Liangshan Mountain Cuculus polioephalus medicine material that obtains with the whole bag of tricks, and/or in a usual manner by its decocting liquid resulting ethanol-soluble extractives composition after the ethanol of higher concentration carries out purification process again, but further experimental result shows, it is 0.935-0.950 that wherein said this volatile oil component is controlled at relative density with employing, and index of refraction is the volatile oil in the 1.500-1.520 scope, and/or the weight content that makes said this decocting get total flavones composition in the ethanol-soluble extractives composition in the liquid is 55.0%-65.0%, and the gross weight of Quercetin wherein and kaempferol is ideal when being the 10.4%-14.3% of total flavones composition weight.
As effective medicinal ingredient,, after corresponding auxiliary adding ingredient mixes, can obtain corresponding form pharmaceutical preparation with above-mentioned extract according to the needs of different preparations.As mixing, can be made into solid type oral formulations such as corresponding tablet, pill, capsule with the various disintegrating agents of using always, excipient, lubricant, binding agent, surfactant, diluent, filler etc.; After the surfactant of using always, diluent, antiseptic, stabilizing agent, correctives, thickening agent etc. mix, can obtain corresponding oral formulations as liquid typees such as water preparation or syrup, or the electuary of corresponding solid particle type.
In above-mentioned said medicine, can be used as the form of one of concrete reference example, be to be effective medicinal ingredient with said volatile oil, mix the oral drugs of composition dropping pill formulation form with the auxiliary adding ingredient of acceptable in the corresponding preparations, its volatile oil content is 20-30 milligram/ball.
Can be used as other example forms of instantiation reference, be that the ethanol-soluble extractives composition of getting in the liquid with said decocting is effective medicinal ingredient, with the medicine of the auxiliary adding ingredient composition of acceptable in corresponding preparations oral formulations form, the content of total flavones composition adopts and counts the 8-12 milligram with Quercetin in each physical location of its pharmaceutical preparation.Here said oral preparation medicament can comprise the oral drug preparation as solid dosage formss such as tablet, hard capsule preparations, also can be oral drug preparations such as above-mentioned liquid dosage form commonly used or corpuscular electuary.Wherein, the implication of each physical location in said each pharmaceutical dosage forms for the medicine of solid preparation form, is meant a slice of pharmaceutical preparation or one etc.; For the medicine of liquid preparation form, what be meant common employing is one of a packaging unit or per 10 grams of granular pattern electuary are a packing unit with per 10 milliliters.
In above-mentioned said medicine, can be used as best a kind of concrete reference example form, be that the ethanol-soluble extractives composition that said effective medicinal ingredient is got in the liquid by said volatile oil component and decocting is formed jointly, and form the oral drugs of dosage forms such as drop pill or soft capsule with the suitable auxiliary adding ingredient of acceptable such as plant wet goods.Wherein, the volatile oil that contains in each physical location of its pharmaceutical preparation is the 8-12 milligram, and also contains the total flavones composition of counting the 8-12 milligram with Quercetin.Wherein the implication of each physical location of said pharmaceutical preparation is the same.
Except that above-mentioned multiple oral drug preparation form example, the above-mentioned medicine of the present invention can also be effective medicinal ingredient for adopting the ethanol-soluble extractives composition of getting in the liquid with said decocting, match with appropriate solvent and additives commonly used in the injection, can also obtain the pharmaceutical preparation of corresponding injection form, be good with the form that adopts the total flavones component content to count the 8-12 mg/ml with Quercetin wherein.
As above-mentioned, Liangshan Mountain Cuculus polioephalus extract as the active drug composition in the said medicine composition of the present invention, can adopt with Liangshan Mountain Cuculus polioephalus is raw material, by the several different methods that has report and/or adopt at present, the volatile oil component that is contained during extraction obtains and/or the ethanol-soluble extractives composition of decocting liquid.Wherein, when but the sacrificial vessel body is implemented with reference to a kind of method that adopts, be to be raw material with Liangshan Mountain Cuculus polioephalus, steam distillation method with usual manner is collected its volatile oil component, again with the ethanol of the aqueous solution in the residue behind the steam distillation with volume content 70%～90%, preferably adopt 75%～85% ethanol to handle, then the alcoholic solution that obtains is removed ethanol, obtain said decocting and get the effective medicinal ingredient of ethanol-soluble extractives in the liquid, the effective medicinal ingredient of ethanol-soluble extractives that resultant volatile oil component and/or decocting are got in the liquid mixes with required ratio consumption with the acceptable complementary adding ingredient of medicine, is prepared into the medicine of corresponding preparations form.
In above-mentioned preparation method, reference mode in the time of can also being further used as enforcement, be said when the aqueous solution in the residue behind the steam distillation is handled with the ethanol of volume content 70%～90%, can adopt is the adsorbent resin of 8-10 nanometer with the aperture with this aqueous solution earlier, the macroporous adsorbent resin of models such as D101 for example commonly used at present or D201 carries out adsorption treatment, and with distilled water thorough washing resin, for example can absorption numerical value be washed with the distilled water of 2-5 times of bed volume usually, and then be that 70%～90% ethanol carries out eluting to adsorbent resin with volume content, and collect ethanol elution.Wave the ethanol that removes or reclaim in the collection liquid, promptly obtain the ethanol-soluble extractives composition of said decocting liquid after ethanol purification is handled.
In addition, said to the aqueous solution in the residue behind this steam distillation during with the Ethanol Treatment of volume content 70%～90%, also can adopt earlier aqueous solution is concentrated, add ethanol alcoholic acid volume content to the mixed solution then and reach 70%～90%, it is fully mixed and post precipitation, collect the mode of clarifying alcoholic solution, proceed the follow-up alcoholic acid processing of removing, can obtain the ethanol-soluble extractives composition of said decocting liquid after ethanol purification is handled equally.Earlier aqueous solution is concentrated before the said herein processing, ethanol consumption when purpose is just used Ethanol Treatment for minimizing is follow-up, therefore said this concentration process be there is no too much requirement here, can be under normal pressure or reduced pressure, the volume of aqueous solution is concentrated into suitable degree gets final product.
Said medicine of the present invention has been carried out following research:
1. ingredient check analysis test
Get the coarse powder 5g of Liangshan Mountain Cuculus polioephalus and Folium Rhododendri Micranthi two medicinal raw material leaves respectively, add the 1g calcium carbonate, add ethanol 50ml, refluxed 2 hours in the water-bath, filter, residue adds ethanol 50ml again, refluxes merging filtrate 1 hour.This ethanol extract of getting half amount is evaporated to 5ml, adds the equivalent distilled water, adds the lead acetate saturated aqueous solution of capacity again, filter, filtrate filters after using sodium sulfate saturated aqueous solution deleading, and filtrate is concentrated into 5ml, chloroform extraction, heat is carried 30 minutes, uses anhydrous sodium sulfate dehydration, behind the evaporate to dryness, residue is dissolved among the methanol 0.25ml, uses for point sample.Get Andromedotoxin-1 (a) and scopoletin target in addition respectively to sighting product (b), with ethanol it is mixed with the solution that concentration is 1mg/ml respectively, as the standard control sample solution.Above-mentioned four kinds of sample liquid behind silica gel G (Haiyang Chemical Plant, Qingdao) thin layer chromatography board end points sample, are advanced development distance 20cm as developing solvent with hexane-methanol-ethyl acetate (volume ratio 5: 1: 4).Make developer with 10% Butter of antimony .-chloroform solution,, show the brownish red speckle in 105 ℃ of oven dry.Be salmon pink person Wei andromedotoxin-1 under the ultra-violet lamp of 254nm wavelength, scopoletin is sapphirine fluorescence.
Get this ethanol extract of other half amount, be evaporated to driedly, the residue hot water wash is concentrated into 5ml, use ethyl acetate extraction, through anhydrous sodium sulfate dehydration, filters, and is evaporated to driedly, and residue is dissolved among the methanol 0.5ml, supplies point sample usefulness.Adsorbent: polyamide film (Huangyan, Zhejiang chemical experiment factory).Developing solvent; Chloroform-butanone-acetylacetone,2,4-pentanedione (16: 1: 5: 1).Exhibition is apart from 8cm.Launch back corresponding speckle in the observation total flavones composition under ultra-violet lamp (254nm).Wherein: a is that the Quercetin of sundown speckle is marked sighting product, and b is the hyperin reference standards of brown speckle.
Above-mentioned thin layer chromatography launches diagram respectively as depicted in figs. 1 and 2.
This result of the test shows, do not contain toxic andromedotoxin-1 in the used Liangshan Mountain Cuculus polioephalus extract of the present invention, but contains the effect scopoletin effective ingredient with cholinolytic and relaxing smooth muscle.
2. acute toxicity testing
(1) Liangshan Mountain Cuculus polioephalus total flavones of medicine of the present invention is to the oral acute toxicity testing of white mice
Healthy nothing is hindered 50 of white mice, body weight 18-22 gram, male and female half and half, fasting was divided into five groups at random by body weight after 12 hours, once irritate stomach by various dose with 40% total flavones solution respectively, under 20 ℃ room temperature, observe to irritate the general activity situation of animal behind the stomach and write down the mortality rate of each treated animal in 24 hours, (Karber) asks its LD with karber's method
50It is 17.83 ± 2.35 grams (being equivalent to 800 gram crude drugs)/kilogram.The LD of Folium Rhododendri Micranthi medicine matched group
50It is 3.25 ± 0.42 grams (being equivalent to 233 gram crude drugs)/kilogram.
(2) Liangshan Mountain Cuculus polioephalus extractum of medicine of the present invention is to the oral acute toxicity testing of white mice.
Healthy do not have hinder 50 of white mice, body weight 18-22 gram, male and female half and half are prohibited, and eat to be divided into five groups at random by body weight after 12 hours, divide 7 continuous irrigation stomaches 7 days by various dose with 50% aqueous extract solution respectively, observe the mortality rate in 3 days, get LD by karber's method
50Be 11.45 ± 1.28 grams (being equivalent to 600 gram crude drugs)/kilogram, the Folium Rhododendri Micranthi matched group is 0.208 ± 0.015 gram (being equivalent to crude drug 25 grams)/kilogram.
(3) Liangshan Mountain Cuculus polioephalus extractum is to anesthetized dog breathing, blood pressure and Electrocardiographic influence
Select healthy do not have hinder, body weight is respectively 10.0 and 14.5 kilograms 2 of male dogs, with the dosage of 3% nembutal, 30 mg/kg, behind the saphena injecting anesthetic, the tracheostomize recording respiration, common carotid artery intubate and hydrargyrum pressure are counted the linkage record blood pressure, lead and V with II
3Chest lead writes down electrocardio respectively to be changed, and experiment is carried out under 30 ℃ of-32 ℃ of room temperatures, imports a small amount of normal saline from vein in the experimentation.
Breathing, blood pressure curve electrocardio (II, the V of record normal (before the administration)
3) after, promptly irritate stomach by 10 milligrams of (being equivalent to crude drug 520 grams)/kg.p.m. secondaries with 30% Liangshan Mountain Cuculus polioephalus extractum, be 1 hour the blanking time of irritating stomach for twice, after irritating stomach, measured blood pressure, breathing, electrocardio respectively once then every 1 hour, METHOD FOR CONTINUOUS DETERMINATION 6 times, result do not find that Cuculus polioephalus filling stomach has a significant effect to blood pressure, breathing and the electrocardio of dog.
3. sub-acute toxicity test
50 of healthy rabbits, 1.5～2.0 kilograms of body weight, male and female half and half are carried out hemogram (hemoglobin, total white blood cells), liver function (glutamate pyruvate transaminase), kidney merit (non-protein nitrogen in the blood), electrocardiogram (II, V respectively
3) after the mensuration, select 34 stochastic sampling of the rabbit of said determination in normal range to be divided into two groups.20 of administration treated animals, irritate stomach once, continuous 45 day with 6 milliliters of 50% extractum liquid (being equivalent to crude drug 314 grams)/kilogram every day; 14 of administration animals are not organized in contrast, two treated animals are weighed weekly once, administration was measured hemogram, hepatic and renal function and electrocardiogram respectively once to two treated animals in the time of one month, and put to death 3 respectively, cored, tissue slice such as liver, spleen, lung, kidney, trachea carries out pathological examination.The result: Liangshan Mountain Cuculus polioephalus does not all have normal effects to rabbit oral medication one month and one and a half months to hepatic and renal function, hemogram and body weight change, and histopathological examination result and matched group relatively there is no unusually.
Above-mentioned toxicity test result shows that the Liangshan Mountain Cuculus polioephalus extract in the medicine of the present invention compares with the Folium Rhododendri Micranthi medicine of existing use at present, and its toxicity is obviously littler, has also proved wherein not Han You andromedotoxin from another angle.
4. pharmacodynamic experiment
(1) mice expectorant test (phenol red method): giving the white mice subcutaneous injection a certain amount of phenol red, is that index is judged expectorant effect, result such as table 1 with phenol red eliminating amount in the trachea.
The expectorant test of table 1 mice (phenol red method) result
| Group | Dosage (being equivalent to the crude drug amount) | Route of administration | The suitable matched group of the phenol red discharge of respiratory tract (%) | The P value | |
| The blank group | ????/ | ?????????/ | ????/ | ????100 | ????/ |
| Medicine of the present invention | Ethanol extraction 50% extractum total flavones | 20g crude drug/kg 20g crude drug/kg 0.6g crude drug/kg | Oral oral | ????170 ????170 ????174 | ??＞0.05 ??＞0.05 ??＞0.05 |
| Folium Rhododendri Micranthi | Total flavones | 50g crude drug/kg | Oral | ????138 | ??＞0.05 |
(2) mice cough-relieving test (ammonia mist method): series causes the mouse cough reaction with spray hydrogenation ammonia mist under the constant-pressure conditions, to cause the spray time (ED of half mouse cough
50) be index, the result is as shown in table 2.
Cough-relieving test (ammonia mist method) result of table 2 mice
| Group | Dosage | Route of administration | ??ED 50 | Judge antitussive action | |
| The blank group | ????/ | ????????????/ | Oral | ???20 | Do not have |
| Medicine of the present invention | Ethanol extraction aqueous extract total flavones | 20g (quite crude drug amount)/kg 20g (quite crude drug amount)/kg 0.6g (quite crude drug amount)/kg | Oral oral | ??250 ??176 ??145 | Effect is obviously arranged |
| Folium Rhododendri Micranthi | Total flavones | 25g (quite crude drug amount)/kg | Oral | ??125 | Effect is arranged |
| Codeine | ?????????0.06g/kg | The abdominal cavity | ??194 | Obviously | |
(3) test of relievining asthma: Cavia porcellus sucks in 1 hour after taking scopoletin that histamine's aerosol causes pants and the tic symptom all has the certain protection effect, but action intensity is not as aminophylline.In addition, isolated ileum segments in guinea pigs is shunk experiment also show, give Liangshan Mountain Cuculus polioephalus aqueous extract 2g (being equivalent to crude drug 105 grams)/kg, spasmolysis is arranged.Its effect organizes the action effect of ammonia, acetylcholine and 5-hydroxyl color ammonia more approaching with anti-.
In addition by cat and the test of rat electricity irritation superior laryngeal nerve are proved that also effective medicinal ingredient Liangshan Mountain Cuculus polioephalus extract of medicine of the present invention has remarkable antitussive effect.Simultaneously, this result shows that also this medicine antitussive effect position has reduced the sensitivity of relevant sensor in the trachea no thanks to, and pointing out its effect may be by directly acting on the result of central nervous system's thing.The expectorant effect of medicine of the present invention is for promoting the mucous function of cilium, and the composition with promotion cilium mucus function may be a contained Quercetin in the Cuculus polioephalus of the Liangshan Mountain.
Medicine of the present invention causes the effect of relievining asthma of breathing heavily to the histamine of Cavia porcellus, illustrate that this medicine has the effect of significantly lax airway smooth muscle, certain anti-acetylcholine, antihistaminic effect are arranged, be because contain the scopoletin composition in effective medicinal ingredient of medicine of the present invention, and scopoletin has the effect of cholinolytic and relaxing smooth muscle, Quercetin in the flavonoid also has report can suppress adrenergic metabolic enzyme-catecholamine oxygen transmethylase, thereby adrenergic destruction is reduced, therefore, the effect that shows lax airway smooth muscle.
In addition, by water extract its unrestraint effect is also found in rabbit PCA test (models of passive skin irritability experiment) to Liangshan Mountain Cuculus polioephalus, the antiasthmatic effect of preliminary this medicine of prompting is little with the immunity relation, and the anti-medium effect of the scopoletin contained with it, Quercetin etc. has than confidential relation.
5. clinical observation
The object of observation: clinical observation 70 examples, chronic bronchitis patient 40 examples wherein, acute bronchitis patient's 16 examples, bronchial asthma patient's 14 examples, wherein male 36 examples, women 34 examples, age 8-75 year, average 54 years old.It is phlegm-heat type that 37 routine Chinese medical discriminations are arranged among the 70 routine patients, and 33 examples belong to cold phlegm type.
Symptom and sign is judged: do not have (-), light (+), obviously (++), serious (+++);
Criterion of therapeutical effect is judged: recovery from illness: symptom and sign disappears; Produce effects: +++→+; Effectively: ++ →+;
Invalid: symptom and sign does not change.
The Therapeutic Method of experiment: all oral oral medicine liquid that contains the pure molten total flavones composition of Liangshan Mountain Cuculus polioephalus decocting liquid of all patients, (general flavone content is in Quercetin 〉=6mg/10ml) for each 10ml, serve on 1-2 week every day 3 times, other related drugs of stopping using during taking.
Experimental therapy result; Oral medicine liquid of the present invention to cough, expectorant, asthma shape has the good curing effect, recovery from illness 28 examples (40%) after 70 routine patient treatment 1-2 weeks, produce effects 13 examples (18.57%), effective 17 examples (24.29%), invalid 12 examples (17.14%), total effective rate are 82.86%.
On this basis, further the above-mentioned oral liquid of the present invention observed of subitem to the coughing of acute/chronic bronchitis, expectorant, the curative effect of three cardinal symptoms such as breathe heavily, the results are shown in Table 3.
Table 3 oral liquid of the present invention is to coughing, expectorant, breathing heavily the curative effect of three primary symptoms
| Symptom | Case load | Produce effects | Effectively | Invalid | Total effective rate | ||||
| The example number | Ratio (%) | The example number | Ratio (%) | The example number | Ratio (%) | The example number | Ratio (%) | ||
| Cough (no expectorant) | ??30 | ????6 | ??20.00 | ????18 | ??60.00 | ????6 | ??20.00 | ????24 | ??80.00 |
| Cough (expectorant is arranged) | ??28 | ????5 | ??17.86 | ????20 | ??71.42 | ????3 | ??10.72 | ????25 | ??89.28 |
| Tachypnea | ??30 | ????5 | ??16.66 | ????18 | ??60.00 | ????7 | ??23.33 | ????23 | ??76.67 |
Medicine of the present invention is as shown in table 4 with the comparing data that has several other Cuculidae medicine Comprehensive Experiment results that use at present.
Table 4 medicine of the present invention and the comprehensive comparison that has several other Cuculidae medicines now
| Kind | Composition | Acute toxicity testing (LD 50)mg/kg | Antitussive action | Phlegm-dispelling functions | Antiasthmatic effect | Andromedotoxin |
| Medicine of the present invention | The extractum total flavones | 11,450 ± 1,280 (suitable 600g crude drug/kg) 17,830 ± 2,350 (suitable 800g crude drugs/kg) | Good | Good | Good | Do not have |
| Folium Rhododendri Micranthi | The extractum total flavones | 208 ± 15 (suitable crude drug 25g/kg 3,259 ± 420 (suitable 233g crude drug/kg) | Generally | Generally | Good | Have |
| Rhododendron | Total flavones | 15,881 ± 1,173 (suitable 750g crude drug/kg) | Good | Good | Generally | Do not have |
| Folium Rhododendri Daurici | Andromedotoxin | 4.50 ± 1.05 (suitable 100g crude drug/kg) | Good | Good | Good | Have |
(annotate: LD
50Value be that mouse stomach is oral)
Above-mentioned experimental result fully shows, treatment acute/chronic bronchitis medicine provided by the present invention is compared with at present used multiple other Cuculus polioephalus class medicine, obviously do not contain the toxic component andromedotoxin, even these medicines that detect with Xian Shi You andromedotoxin compare, not only toxicity is significantly lower, safety greatly improves, and also obviously is better than these medicines in antitussive, aspect the comprehensive effect such as eliminate the phlegm, relieving asthma.Simultaneously,, fully improved the utilization rate of medicine material, also helped the raising of curative effect of medication because various forms of effective medicinal ingredients such as volatile oil in the Cuculus polioephalus medicinal raw material of the Liangshan Mountain and total flavones can both be fully used.Adopt in preparation method particularly that the macroporous resin technology is extracted, the total flavones of separation and purification effective site, make the active constituent content that to survey greater than 50%, remove impurity to greatest extent, keep effective ingredient, significantly reduce dose, solved thick, big, the black problem of Chinese medicine.
According to foregoing,,, can also make modification, replacement or the change of various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.
Below in conjunction with the specific embodiment, foregoing of the present invention is described in further detail again by the accompanying drawing illustrated embodiment.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Description of drawings
Fig. 1 is a medicine of the present invention and a kind of thin layer chromatography expanded view of similar medicine ingredient.Among the figure: a is an Andromedotoxin-1, and b is a scopoletin; 1. the medicinal liquid sample of Liangshan Mountain Cuculus polioephalus extract, 2. the medicinal liquid sample of Folium Rhododendri Micranthi extract, 3. the medicinal liquid sample of Rhododendron extract, 4. the medicinal liquid sample of Folium Rhododendri mariae extract
Fig. 2 is a medicine of the present invention and the thin layer chromatography expanded view of the contained total flavones composition of similar medicine.Among the figure: a is a Quercetin; B is a hyperin; 1. the medicinal liquid sample of Liangshan Mountain Cuculus polioephalus extract, 2. the medicinal liquid sample of Folium Rhododendri Micranthi extract, 3. the medicinal liquid sample of Rhododendron extract, 4. the medicinal liquid sample of Folium Rhododendri mariae extract
The specific embodiment
Example 1 oral medicine liquid preparation
Get Liangshan Mountain Cuculus polioephalus 1000g, add 12 times in water, feed steam and distill, volatile oil was extracted in continuous still in 6 hours, and the volatile oil of collecting is filtered, and placed Brown Glass Brown glass bottles and jars only, and it is stand-by to deposit in 4 ℃ of refrigerators.Medicinal residues add 10 times of decoctings and boiled 1 hour, filter, filtrate is condensed into the clear paste that relative density is 1.1-1.2 (70-80 a ℃), add an amount of citric acid and adjust pH value to～4.5, the adding clear paste weighs the gelatin solution of 3 times of amounts 2%, and the limit edged stirs, after reacting fully, adding ethanol, to make content (v/v) be 70-90%, the best can be 75-85%, leaves standstill 72 hours, filters, decompression filtrate recycling ethanol concentrates and ends about 600ml, left standstill 24 hours, and filtered, filtrate is with sucrose and sodium benzoate, boil and make dissolving, add water to 1000ml.Filter, embedding, sterilization, promptly.This oral liquid includes total flavones in Quercetin, and quercetin content is 0.8-1.2mg/ml.
Example 2 injection pharmaceutical preparatioies
Get Liangshan Mountain Cuculus polioephalus 1000g, add 12 times of apyrogenic distilled water, feed steam and distill, volatile oil was extracted in continuous still in 6 hours, and the volatile oil of collecting is filtered, and placed Brown Glass Brown glass bottles and jars only, and it is stand-by to deposit in 4 ℃ of refrigerators.Medicinal residues add 10 times of apyrogenic distilled water and decocted 1 hour, filter, and add apyrogenic distilled water and end 6000ml.The every 250ml medicinal liquid of mixing is equivalent to the 10g medical material, behind the absorption with macroporous adsorbent resin that models such as D101 commonly used that the aperture is the 8-10 nanometer or D201 are housed, with unconjugated composition of the distilled water wash of 2-5 times of bed volume and impurity, with ethanol (v/v) eluting of 75.0%-85.0% and collect ethanol elution, the eluent decompression recycling ethanol ends to be done, vacuum drying gets dry powder, and its general flavone content is 55.0%-65.0% (w/w).Wherein the total content of Quercetin and kaempferol is 10.4%-14.3%.Get dry powder and add injection water dissolving 100ml, transfer PH6-7, added for 0.5% activated carbon adsorption half an hour, filter, filtrate adds proper amount of water for injection and to volume is, fine straining, embedding in ampoule, 100 ℃ of sterilizations in 30 minutes, promptly.Adopt the colorimetric method for determining content of total flavone, the HPLC method is measured the content of Quercetin and kaempferol, and its content is that the total content of Quercetin and kaempferol must not be less than 8-12mg/ml, is equivalent to crude drug 1.0g-1.5g.
Example 3 drop pill pharmaceutical preparatioies
Polyethylene Glycol (PEG) 6000 is heated to whole thawings in water-bath after, add as stated above through the Liangshan Mountain of macroporous resin extraction Cuculus polioephalus extract thick paste, stir, add Liangshan Mountain Cuculus polioephalus volatile oil mixing immediately, be transferred in the reservoir rapidly, airtight and insulation splashes in the refrigerative methyl-silicone oil at 80 ℃, collects drop pill, the methyl-silicone oil on surface is removed in suction, drying, packing, promptly.The heavy 40mg-50mg of the every ball of this drop pill, volatile oil and quercetin content are the 8mg-12mg/ ball
Example 4 soft gelatin pharmaceutical preparations
Through the Liangshan Mountain of macroporous resin extraction Cuculus polioephalus extract, be condensed into thick paste with as stated above, vacuum drying is ground into fine powder and sieves, and adds Liangshan Mountain Cuculus polioephalus volatile oil and an amount of refining practical vegetable oil, and mill is spared, sieved, and is pressed into soft gelatin capsule with encapsulating machine.Its medicine consists of: the Liangshan Mountain Cuculus polioephalus volatile oil 10g that obtains as stated above, and Liangshan Mountain Cuculus polioephalus total flavones 175g, vegetable oil 165g makes 1000 altogether.Every is 0.35g, and wherein containing volatile oil component is 8mg-12mg, and containing Quercetin is 8mg-12mg, is equivalent to crude drug 1.0g-1.5g/ grain.
Discrimination test: adopt thin layer chromatography discriminating flavones ingredient wherein.Remove this product content 3g, add dehydrated alcohol 20ml, close plug, supersound process 30 minutes filters, and filtrate is concentrated into 2ml, as need testing solution.Other gets Liangshan Mountain Cuculus polioephalus control medicinal material 1.0g, uses with legal system and shines medical material solution in pairs.Get the Quercetin reference substance again, add ethanol and make the solution that every 1ml contains 1mg, solution in contrast.Carry out according to thin layer chromatography (2000 editions appendix VIB of Chinese Pharmacopoeia) test, promptly draw each 10 μ l of above-mentioned three kinds of solution, putting in same sodium carboxymethyl cellulose respectively is on the silica gel g thin-layer plate of binding agent, with toluene-chloroform-acetone-formic acid (volume ratio=8: 5: 7: 1) be developing solvent, launch, take out, dry, with control medicinal material, the corresponding position of reference substance chromatograph on, show the speckle of same color.Spray places under the certain wavelength of uviol lamp and inspects with aluminum chloride reagent, in the test sample chromatograph, respectively with control medicinal material and contrast chromatograph corresponding position on, show the fluorescence speckle of same color.
Assay: adopting the HPLC method, is filler with the octadecylsilane bonded silica, and methanol-phosphoric acid is that mobile phase detection wavelength is that the 370nm theoretical cam curve should be not less than 4000 by the calculating of Quercetin peak.Get this product content 3g, add dehydrated alcohol 20ml, close plug, supersound process 30 minutes filters, and filtrate is concentrated into 2ml, as need testing solution.Other gets Liangshan Mountain Cuculus polioephalus control medicinal material 1.0g, uses with legal system and shines medical material solution in pairs.Get the Quercetin reference substance again, add ethanol and make the solution that every 1ml contains 1mg, solution in contrast.Draw each 10 μ l of above-mentioned three samples respectively, inject on the chromatographic column respectively and measure, promptly.The content of Quercetin should be no less than 5mg/ml.
Claims (10)
1. a medicine for the treatment of acute/chronic bronchitis is characterized in that the extract with Liangshan Mountain Cuculus polioephalus is effective medicinal ingredient, forms with acceptable complementary adding ingredient mixed together in the medicine.
2. the medicine of treatment acute/chronic bronchitis as claimed in claim 1, it is characterized in that said effective medicinal ingredient gets at least a in the ethanol-soluble extractives composition in the liquid for the volatile oil component that extracted by Liangshan Mountain Cuculus polioephalus medicine material and decocting, wherein the relative density of said this volatile oil component is 0.935-0.950, index of refraction is 1.500-1.520, the weight content that said this decocting is got total flavones composition in the ethanol-soluble extractives composition in the liquid is 55.0%-65.0%, and the gross weight of Quercetin wherein and kaempferol is the 10.4%-14.3% of total flavones composition weight.
3. the medicine of treatment acute/chronic bronchitis as claimed in claim 2, it is characterized in that with said volatile oil be effective medicinal ingredient, mix the oral drugs of forming the dropping pill formulation form with acceptable auxiliary adding ingredient in the medicine, its volatile oil content is 20-30 milligram/ball.
4. the medicine of treatment acute/chronic bronchitis as claimed in claim 2, it is characterized in that the ethanol-soluble extractives composition of getting in the liquid with said decocting is effective medicinal ingredient, with the oral preparation medicament that acceptable auxiliary adding ingredient in the medicine is formed, the content of total flavones composition adopts and counts the 8-12 milligram with Quercetin in each physical location of its pharmaceutical preparation.
5. the medicine of treatment acute/chronic bronchitis as claimed in claim 2, it is characterized in that the ethanol-soluble extractives composition that said effective medicinal ingredient is got in the liquid by volatile oil component and decocting forms jointly, the oral drugs that acceptable auxiliary adding ingredient is formed in itself and the medicine, wherein its content is to contain volatile oil 8-12 milligram in each physical location of pharmaceutical preparation, also contains the total flavones composition of counting the 8-12 milligram with Quercetin.
6. the medicine of treatment acute/chronic bronchitis as claimed in claim 5 is characterized in that said oral drugs are a kind of in dropping pill formulation or the soft capsule preparation form medicine.
7. the medicine of treatment acute/chronic bronchitis as claimed in claim 2, it is characterized in that the ethanol-soluble extractives composition of getting in the liquid with said decocting is effective medicinal ingredient, the medicine of the injection form of forming with acceptable auxiliary adding ingredient in the medicine, total flavones component content wherein is in Quercetin 8-12 mg/ml.
8. the method for preparing the described treatment acute/chronic bronchitis of claim 1 medicine, it is characterized in that with Liangshan Mountain Cuculus polioephalus be raw material, steam distillation method with usual manner is collected its volatile oil component, again with the Ethanol Treatment of the aqueous solution in the residue behind the steam distillation with volume content 70%～90%, then the alcoholic solution that obtains is removed ethanol, obtain said decocting and get the effective medicinal ingredient of ethanol-soluble extractives in the liquid, the effective medicinal ingredient of ethanol-soluble extractives that resultant volatile oil component and/or decocting are got in the liquid mixes with required ratio consumption with the acceptable complementary adding ingredient of medicine, is prepared into the medicine of corresponding preparations form.
9. preparation method as claimed in claim 8, it is characterized in that said to the aqueous solution in the residue behind the steam distillation during with the Ethanol Treatment of volume content 70%～90%, can adopt earlier this aqueous solution is that the adsorbent resin of 8-10 nanometer is made adsorption treatment with the aperture, and with behind the distilled water thorough washing resin, the reuse volume content is that 70%～90% ethanol carries out eluting to adsorbent resin and handles and collect ethanol elution.
10. preparation method as claimed in claim 8, it is characterized in that said to the aqueous solution in the residue behind the steam distillation during with the Ethanol Treatment of volume content 70%～90%, adopt earlier aqueous solution is concentrated, add ethanol alcoholic acid volume content to the mixed solution then and reach 70%～90%, it is fully mixed and post precipitation, collect clarifying alcoholic solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031356303A CN1513518A (en) | 2003-08-21 | 2003-08-21 | Medicine for treating acute chronic bronchitis and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031356303A CN1513518A (en) | 2003-08-21 | 2003-08-21 | Medicine for treating acute chronic bronchitis and its preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1513518A true CN1513518A (en) | 2004-07-21 |
Family
ID=34240038
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031356303A Pending CN1513518A (en) | 2003-08-21 | 2003-08-21 | Medicine for treating acute chronic bronchitis and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1513518A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115192624A (en) * | 2022-05-23 | 2022-10-18 | 成都杨天万应制药有限公司 | Extraction process and application of rhododendron Liangshan |
-
2003
- 2003-08-21 CN CNA031356303A patent/CN1513518A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115192624A (en) * | 2022-05-23 | 2022-10-18 | 成都杨天万应制药有限公司 | Extraction process and application of rhododendron Liangshan |
| CN115192624B (en) * | 2022-05-23 | 2023-10-13 | 成都杨天万应制药有限公司 | Extraction process and application of rhododendron simsii |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102657823A (en) | Traditional Chinese medicine composition with anticancer effect and preparation method and detection method thereof | |
| CN1872106A (en) | Application of wild basil circle leaves in treating disease of virulence cold | |
| CN101045072A (en) | Extractive of turnipia arguta leaves and its pharmaceutical use | |
| CN1817898A (en) | Use of anti-inflammatory medicine for scheelite total saponin and its saponin compound | |
| CN1269498C (en) | Chinese medicinal composition possessing antipyretic and its preparation method and quality control method | |
| CN1233378C (en) | Chinese medicine composition for treating oral cavity and throat diseases and its preparing method | |
| CN1141101C (en) | Chinese medicine for treating hepatitis B and its preparing process | |
| CN1876045A (en) | A Chinese medicinal composition, its preparation process and quality control method | |
| CN1961898B (en) | An antitumor compound pharmaceutical composition with barbed stullcap and preparation process thereof | |
| CN1292750C (en) | Total alkaloid composition from plant and its pharmaceutical preparation | |
| CN100998687B (en) | Medicine composition for treating chronic gastritis, and its preparing process | |
| CN1513518A (en) | Medicine for treating acute chronic bronchitis and its preparation method | |
| CN101411779A (en) | Chinese medicine effective component composition for treating liver cancer and method for preparing the same | |
| CN1181855C (en) | Hypericum perforatum extract and its prepn process and medicine composition | |
| CN1736435A (en) | Chinese medicinal preparation for treating rhinitis and preparation process thereof | |
| CN1193766C (en) | Gardenia total glycoside composite for curing hepatitis and its preparation method | |
| CN1264506C (en) | Pharmaceutical combination containing red sage root element and preparation method thereof | |
| CN1785212A (en) | Novel cinobufogenin freeze-drying powder injection, its prepn. method and quality control method | |
| CN1416880A (en) | New use of powder for regulating liver and spleen and its active part | |
| CN1872101A (en) | Distillage of Ardisia chinensis Benth of possessing function of antivirus, distilling method and application | |
| CN1220510C (en) | Chinese patent medicine with the functions of replenishing qi and blood and nourishing the heart to calm the mind, its preparation method and quality control method | |
| CN1961894B (en) | A novel compound pharmaceutical composition, preparation method and use thereof | |
| CN1768770A (en) | Quality control method of agavaceae extract medicinal formulation | |
| CN104688723A (en) | Application of anhydroicaritin in preparation of medicine for treating anaemia | |
| CN1207002C (en) | Antineoplastic composite and its prepn process and use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |