CN101028323A - Chinese-medicinal composition for treating cough asthma - Google Patents
Chinese-medicinal composition for treating cough asthma Download PDFInfo
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- CN101028323A CN101028323A CN 200710063724 CN200710063724A CN101028323A CN 101028323 A CN101028323 A CN 101028323A CN 200710063724 CN200710063724 CN 200710063724 CN 200710063724 A CN200710063724 A CN 200710063724A CN 101028323 A CN101028323 A CN 101028323A
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- angelicae sinensis
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Abstract
A Chinese medicine for treating cough and asthma contains the extract of common alstonin leaf (5-90%) and the volatile of Chinese angelica root (10-95%).
Description
Technical field
The present invention relates to a kind of Chinese medicine composition, the component of said composition is Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris extract, and it is mainly used in diseases such as treatment cough, asthma.
Background technology
Cough, asthma is common respiratory passage diseases, and pathogenic factor is more.
Cough is one of modal symptom in the respiratory system; it is a kind of protective measure of human body; to body is useful; when respiratory mucosa is subjected to foreign body, inflammation, secretions or anaphylaxis factor etc. and stimulates; be that reflexive ground causes cough, help to get rid of from extraneous foreign body of invading respiratory tract or secretions, the elimination respiratory tract factor., then lose its protectiveness meaning as for frequent irritable cough causes the work of influence and rest.Suddenly the cough of Fa Shenging, many because acute upper respiratory tract inflammation (person due to particularly irritative gas sucks) and trachea or foreign body in bronchus cause.Theory of Chinese medical science is thought: cough is by six climate exopathogens exopathogen invasion and attack lung system, or visceral dysfunction, in injure lung, impaired depurative descending of lung QI, due to the abnormal rising of lung-QI, clinical with cough, coughing up phlegm is main performance.
Bronchial asthma is that a kind of airway allergy inflammation and airway hyperreactivity based on eosinophilic granulocyte, mastocyte reaction is the disease of feature.The susceptible person shows as in various degree reversibility airway obstruction symptom to this type of inflammation.After having the people of allergic constitution to contact antigen, make smooth muscle that spasm take place immediately, this is that speed is sent out the property asthma reaction.More commonly many patients start at contact antigen a few hours and even several 10 hours rear and make asthma, are called late asthmatic response, and this is the result of airway allergy inflammation.During air flue myxedema, inflammatory cell infiltration, glandular secretion increase, the mucociliary clearance dysfunction, add in the tube chamber that it also is the important mechanisms of asthma attack that mucous plug blocks.Repeated relapsing can be alleviated voluntarily or after the treatment with the expiratory dyspnea of wheezing sound, uncomfortable in chest or cough.
According to having or not the different of anaphylactogen and age of onset, be divided into extrinsic asthma and intrinsic asthma clinically.Fall ill when extrinsic asthma is everlasting childhood, teenager, family's allergies are arranged more, be the I allergic reaction type.The then many no known anaphylactogens of intrinsic asthma in adult's morbidity, do not have obviously seasonality, and rare allergies may be caused by focus of infection in the body.Which kind of asthma no matter, light disease spontaneous remission gradually, the catabasis does not have any symptom or unusual sign.
Theory of Chinese medical science is thought: bronchial wheezing is because retained phlegm volt lung, meet inducement or sense heresy and draw and touch, so that the stagnation of phlegm air flue, impairment of purifying and descending function of the lung, paroxysmal rale asthma illness due to the air flue contraction is anxious.Whistling sound in the throat during outbreak, tachypnea and dyspnea, very then failing to lie flat due to dyspnea is main performance.
The syndrome of dyspnea is with dyspnea, the tachypnea of panting, even opening mouth and lifting shoulder due to dyspnea, flaring of nares, and can not put down crouches is the disease of main clinical manifestation.The syndrome of dyspnea is not an independent disease, but a symptom is found among the multiple disease, it is a kind of illness with symptom performance name, usually concurrent in the process of multiple acute and chronic diseases, when breathing heavily the main symptom that becomes a certain stage of these diseases, then be referred to as the syndrome of dyspnea.
The medicine that is used for the treatment of diseases such as cough, asthma now is a lot, there is chemical medicine that Chinese medicine is also arranged, chemistry medicine good effect but often side effect is big, Chinese medicine is as tetrahydro-isoquinolin, the curing capsule of panting, FUFANG GANCAO PIAN, Dingchuan antitussive ball etc., in clinical practice, mostly not remarkable because of curative effect, preparation is coarse, quality is wayward, stability of drug products is relatively poor, or because add Herba Ephedrae in the prescription, malicious anaesthetic thing such as Semen Papaveris, take for a long time and make the people produce drug dependence, or produce side effect such as drug resistance owing to having added chemistry or hormones constituents with function of relieving cough and calming asthma, cause it can not long-term clinical application, this shows that pure Chinese medicinal preparation (not containing dependent malicious anaesthetic thing and chemistry or hormones composition) truly still is in relative weak tendency in cough comparatively speaking with treating asthma market.Good effect, the side effect low characteristics of Chinese medicine in disease treatment do not demonstrate fully out, this wherein has the reason of prescription, the reason that technology is more arranged, so a kind of reasonable recipe, technology advanced person, steady quality, determined curative effect, remarkable, safe treatment cough and the pure Chinese medicine medicine of asthma disease are developed in market in urgent need.
Summary of the invention
The inventor comes from theory of Chinese medical science, sums up experience in many ways, forms through the empirical sanction of testing in a large number and getting in the past.The present invention is a Chinese medicine composition, is refining through extraction by two flavor Chinese medicines and pure Chinese medicinal preparation that make, and determined curative effect is safe and reliable.
The object of the present invention is to provide a kind of Chinese medicine composition and comprise the medicine of said composition, this medicine can be treated diseases such as cough, asthma.
The present invention also aims to provide manufacturing method for above mentioned medicine, by this method, can obtain being used for the treatment of cough, asthma evident in efficacy, technology is advanced, stay-in-grade pharmaceutical composition.
The present invention also aims to provide aforementioned pharmaceutical compositions to be used for the treatment of the purposes of diseases such as cough with asthma.
In order to achieve the above object, the invention provides a kind of Chinese medicine composition, component is made up of Radix Angelicae Sinensis extract and Folium Alstoniae Scholaris extract in the said composition, wherein Radix Angelicae Sinensis extract is a Radix Angelicae Sinensis volatile oil, the present composition is made up of the component of following weight proportion: Radix Angelicae Sinensis volatile oil 5-90%, Folium Alstoniae Scholaris extract 95-10%; Contain the ligustilide that accounts for Radix Angelicae Sinensis volatile oil gross weight 30-80% in the described Radix Angelicae Sinensis volatile oil, comprise in the described Folium Alstoniae Scholaris extract and contain the indoles alkaloid that accounts for this extract gross weight 1-90%, contain the duck hornbeam leaf alkali that accounts for this extract gross weight 0.1-80% in this indoles alkaloid.
In the compositions of the present invention, also can select the whole starch of flavour of a drug, also can extract the back is used as medicine with the form of extract, be preferably that Radix Angelicae Sinensis extracts volatile oil, Folium Alstoniae Scholaris is that water or alcohol extract are used as medicine, as long as comprised the effective ingredient of Radix Angelicae Sinensis and Folium Alstoniae Scholaris, said composition can reach the drug effect of treatment cough and asthma.
Through a large amount of proportioning tests, and the affirmation experiment of carrying out best proportioning, in a preferred embodiment of the invention, the component of aforementioned pharmaceutical compositions and proportioning are the part by weight preferred 1 of Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris extract: 4-15, wherein, the part by weight of Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris water extract preferred 1: 12-15, most preferably 1: 13, the part by weight preferred 1 of Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris ethanol extraction: 4-5.
The invention provides a kind of medicine for the treatment of the cough, asthma disease, it comprises above-mentioned Chinese medicine composition and pharmacy acceptable auxiliary, according to the difference of pharmaceutical dosage form, selected adjuvant is also different, in this pharmaceutical preparation, the content in Radix Angelicae Sinensis effective ingredient ligustilide is at least 10mg/g.
Above-mentioned pharmaceutical preparation can be any dosage form, is preferably peroral dosage form, and it is that on the pharmacy meaning all can supply oral dosage form, preferred particulates agent, capsule, tablet, oral liquid and syrup; Because the effective site of Radix Angelicae Sinensis is based on volatile oil; in order to protect effective ingredient not to be destroyed; the present invention adopts the beta-cyclodextrin inclusion compound technology that Radix Angelicae Sinensis volatile oil is carried out enclose; characteristics according to said composition; and preparation should safety; effectively, consideration such as taking convenience, in an embodiment of the present invention, more preferably granule, tablet and capsule.Experimental results show that, the curative effect of medicine of the present invention obviously is better than existing treatment cough, asthma disease Chinese patent medicine (as: Dingchuan antitussive ball) preferably, by comparison, the present composition has reduced the flavour of a drug of the Chinese patent medicine of existing treatment cough with asthma and has formed, farthest reduce dosage, and improved drug effect.
The present invention also provides the preparation method of aforementioned pharmaceutical compositions, may further comprise the steps: get the Radix Angelicae Sinensis medical material, adopt the way of distillation or supercritical fluid extraction Radix Angelicae Sinensis volatile oil; Get the Folium Alstoniae Scholaris medical material, the additive polarity solvent extraction obtains the Folium Alstoniae Scholaris extract, and described polar solvent is that water or concentration are the ethanol of 10-95%, and described extraction comprises decoction and/or refluxes; The Radix Angelicae Sinensis volatile oil and the Folium Alstoniae Scholaris extract that obtain are mixed.
The present invention preferably with Radix Angelicae Sinensis volatile oil water or ethanol as solvent, make the process of volatile oil clathrate compound with beta-cyclodextrin inclusion compound, wherein the part by weight of volatile oil and beta-schardinger dextrin-is 1: 5-10.
For being for the Folium Alstoniae Scholaris of effective ingredient with the indoles total alkaloids, the active constituent content of the extract that obtains with alcohol extraction is far above the extract that obtains with water extraction, certainly can improve the content of the indoles alkaloid in the Folium Alstoniae Scholaris extract after water (the general method of extracting that decocts that adopts) extracts by process for refining, but take all factors into consideration, in order to improve alkaloidal productive rate, preferably adopt ethanol to extract Folium Alstoniae Scholaris as solvent.When the extraction solvent of Folium Alstoniae Scholaris adopted concentration to be the ethanol of 10-95%, preferably with the Folium Alstoniae Scholaris alcohol reflux, for example the 50-95% alcohol reflux concentrated, and water precipitating obtains the Folium Alstoniae Scholaris extract.Resulting Folium Alstoniae Scholaris extract is through filtering, or filtrate crosses macroporous adsorbent resin (comprising models such as D101, AB-8, HP20), washes the reaction negative to molish earlier with water, the reuse ethanol elution, and eluent reclaims, and concentrates drying under reduced pressure; Or filtrate adds hydrochloric acid and transfers pH to 3-4, filters, and supernatant is crossed 732 type cation exchange resin columns, with 10 times of volume water washings, discard cleaning mixture, with 1 times of column volume strong aqua ammonia alkalization post, with 6 times of volume 30～50% ethanol elutions, collect eluent, concentrating under reduced pressure and cold drying; Or concentrated, pulverizing, last preparation of silica gel post with chloroform-methanol (20: 1) eluting, is collected eluent, reclaims solvent, gets extract.Contain the indoles alkaloid that accounts for this extract gross weight 1-90% in the Folium Alstoniae Scholaris extract that collection obtains, contain the duck hornbeam leaf alkali that accounts for this extract gross weight 0.1-80% in this indoles alkaloid.If process for refining without column chromatography, indoles alkaloid generally accounts for the 1-10% of Folium Alstoniae Scholaris extract gross weight, if but refining through column chromatography or recrystallization repeatedly, indoles alkaloid generally can account for the 10-90% of Folium Alstoniae Scholaris extract gross weight, also can obtain the Folium Alstoniae Scholaris extract for the purpose method in order to extraction and enrichment indoles alkaloid, this indoles alkaloid can account for about 90% of Folium Alstoniae Scholaris extract gross weight.In like manner, if through the refining of column chromatography or recrystallization repeatedly or with the purification indoles alkaloid is that the purpose method obtains indoles alkaloid, picrinine also can obtain suitable Folium Alstoniae Scholaris extract gross weight 80% or surpass 80%, even reach 90%, generally speaking, minimum 0.1% (for example decocting boils the Folium Alstoniae Scholaris extract that obtains) that accounts for Folium Alstoniae Scholaris extract gross weight of duck hornbeam leaf alkali in the purified Folium Alstoniae Scholaris extract is generally 0.1-10%.
The method that the present invention also provides a kind of preparation to contain the medicine of above-mentioned composition, comprising:
(1) gets the Radix Angelicae Sinensis medical material, adopt the method preparation of the way of distillation or supercritical extraction, get Radix Angelicae Sinensis volatile oil;
(2) get the Folium Alstoniae Scholaris medical material, the additive polarity solvent extraction obtains the Folium Alstoniae Scholaris extract, and described polar solvent is that water or concentration are the ethanol of 10-95%, and described extraction comprises decoction and/or refluxes.
(3) Radix Angelicae Sinensis volatile oil with above-mentioned (1) mixes with the extract that (2) obtain;
(4) add pharmacy acceptable auxiliary mixing.
Above-mentioned steps preferably adopts the ethanol of 50-95%, more preferably also comprises resulting Folium Alstoniae Scholaris extract is filtered, and filtrate is crossed macroporous adsorbent resin (for example D101, AB-8 or HP20), wash reaction negative earlier with water to molish, the reuse ethanol elution, eluent reclaims, concentrate drying under reduced pressure; Or filtrate adds hydrochloric acid and transfers pH to 3-4, filters, and supernatant is crossed 732 type cation exchange resin columns, with 10 times of volume water washings, discard cleaning mixture, with 1 times of column volume strong aqua ammonia alkalization post, with 6 times of volume 30～50% ethanol elutions, collect eluent, concentrating under reduced pressure and cold drying; Or concentrated, pulverizing, last preparation of silica gel post with chloroform-methanol (20: 1) eluting, is collected eluent, reclaims solvent, gets extract.
In a preferred embodiment of the invention, be example with the capsule, the described capsular preparation method that contains above-mentioned composition comprises:
(1) gets the Radix Angelicae Sinensis medical material, adopt the way of distillation or supercritical fluid extraction Radix Angelicae Sinensis volatile oil;
(2) get the Folium Alstoniae Scholaris medical material, decoct with water 2 times, each 2 hours, collecting decoction filtered, and filtrate is concentrated into relative density 1.3, added ethanol to containing alcohol amount 65%, left standstill 24 hours, got supernatant and reclaimed ethanol, was spray dried to powder, got the Folium Alstoniae Scholaris extract; Perhaps
Get the Folium Alstoniae Scholaris medical material, add alcohol reflux 2 times, each 1.5 hours, close ethanol liquid, filter, filtrate recycling ethanol also is concentrated into the thick paste shape, and drying under reduced pressure gets the Folium Alstoniae Scholaris extract; Perhaps
Get the Folium Alstoniae Scholaris medical material, add alcohol reflux 2 times, each 1.5 hours, close ethanol liquid, filter, filtrate recycling ethanol also is concentrated into certain volume, adds the water of 2 times of amounts, stirs, and leaves standstill 24 hours.Filter, filtrate is concentrated into the thick paste shape, and drying under reduced pressure gets the Folium Alstoniae Scholaris extract; Perhaps, more preferably
Get the Folium Alstoniae Scholaris medical material, add alcohol reflux 2 times, each 1.5 hours, close ethanol liquid, filter, filtrate recycling ethanol also is concentrated into certain volume, adds the water of 2 times of amounts, stirs, and leaves standstill 24 hours.Filter, filtrate is crossed macroporous resin, washes the reaction negative to molish earlier with water, the reuse ethanol elution, and eluent reclaims ethanol and is concentrated into the thick paste shape, and drying under reduced pressure gets the Folium Alstoniae Scholaris extract.
(3) extract that above-mentioned clathrate (1) and (2) are obtained mixes;
(4) encapsulating capsule.
For obtaining the pharmaceutical composition that active component is more stable, active constituent content is higher, preferred available water of the Radix Angelicae Sinensis volatile oil of above-mentioned preparation method or alcohol are made volatile oil clathrate compound as solvent with beta-cyclodextrin inclusion compound.
According to this area routine techniques, compositions of the present invention is preferably capsule, tablet, granule, also can be made into honeyed pill, water-honeyed pill, the watered pill, paste pill, wax pill, concentrated pill, its processing step is routine operation, visual medical material situation difference takes the circumstances into consideration to change process conditions, and it is conventionally known to one of skill in the art.
At the difference of needed product, the preparation process of medicine of the present invention also can be different, but are the common practise preparation process, describe no longer one by one.For example, when needs prepared the condensed water honeyed pill, this step also can comprise with the hydromel of 5%-25% carried out (comprising crude drug powder and extract dry extract etc.) process of general system to dried medicated powder, to make condensed water honeyed pill product; Again for example: the condensed water honeyed pill generally also will polish through behind the general ball, and drying can obtain final product.
In above-mentioned preferred embodiment, the concrete parameter designing of preparation were established is according to different Chinese crude drug character and pharmacological action difference, determines with screening by analysis.For example, contain multiple volatile oil and fat-soluble effective ingredient in the Radix Angelicae Sinensis, volatile oil is volatile, will improve the stability of volatile oil component behind its enclose greatly, and it is more complete that it is absorbed.Prove that through pharmacological experiment it is rational selection process scheme.The technical conditions of water or alcohol extraction Folium Alstoniae Scholaris (optimum technology parameter of extraction) are with paste-forming rate and indoles alkaloid, especially wherein picrinine (one of effective ingredient of Folium Alstoniae Scholaris) content is index, adopts four factors, three water-glasses to carry out that orthogonal test determines.
The Chinese crude drug that is adopted in the compositions of the present invention is the medical material that version pharmacopeia in 2000 is recorded, and through identifying, every index all meets the pharmacopeia regulation.
The physical and chemical identification of compositions of the present invention and medicine: wherein the assay of indoles alkaloid is according to titration measuring (with reference to the assay method of total alkaloids), the content of picrinine is to adopt high effective liquid chromatography for measuring, and the content of ligustilide is to adopt gas chromatography determination.Evidence, this method sensitivity, favorable reproducibility, in compositions of the present invention, (content 0.4g or 0.27g) is example with capsule, the effective ingredient of every capsules should contain ligustilide and be at least 8mg; Contain indoles alkaloid and be at least 10mg; Contain picrinine and be at least 50 μ g, the weight of every capsules is no more than 0.4g (0.4g is No. 0 capsule).
The effective ingredient of Radix Angelicae Sinensis is a Radix Angelicae Sinensis volatile oil among the present invention, based on ligustilide, generally accounts for 60% of volatile oil, can adopt the thin layer chromatography qualitative identification, gas chromatography or liquid chromatograph standard measure, and concrete grammar is as follows:
Chromatographic condition: with octadecylsilane chemically bonded silica is filler; Methanol-1.2% acetic acid (55: 45) is mobile phase, and the detection wavelength is 280nm.
The preparation of reference substance solution: it is an amount of to get the ligustilide reference substance, and accurate the title decides, and adds methanol and makes the solution that every ml contains 0.25mg, promptly.
The preparation of need testing solution: get the product content thing 1g of embodiment 1, the accurate title, decide, and puts in the 25ml measuring bottle, adds an amount of supersound process of methanol 20 minutes, and be centrifugal, filters, promptly.
Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly.
The Folium Alstoniae Scholaris extract component is mainly indoles alkaloid, as duck hornbeam leaf alkali etc.Can adopt the thin layer chromatography qualitative identification, high effective liquid chromatography for measuring duck hornbeam leaf alkali content, titration measuring indoles alkaloid content.
The inspection of arsenic salt and heavy metal in the medicine of the present invention: press one one of Chinese Pharmacopoeia version in 2000, appendix IX E, IX F item be regulation down, the arsenic salt and the heavy metal of this product 3 batch samples is checked the result is in prescribed limit.
Health examination in the medicine of the present invention:, meet pharmacopeia hygiology standard through health examination.
The present invention also provides the application of above-mentioned composition in preparation treatment cough suppressing panting calming medicine.
The clinical dosage of medicine granule of the present invention is recommended as 2g/ time, 3 times/day.
The combination of Radix Angelicae Sinensis volatile oil of the present invention and Folium Alstoniae Scholaris extract, evidence can obtain extraordinary cough-relieving and antiasthmatic effect, illustrate that it is not simple curative effect summation action but collaborative potentiation that The combined is used, this conclusion also can make up its pharmacological action and effect from simple Radix Angelicae Sinensis volatile oil (or Folium Alstoniae Scholaris extract) and other Chinese medicine extract with antiasthmatic effect and obviously observe not as combined effect of the present invention and draw, and it has proved the present invention that from another angle Radix Angelicae Sinensis and Folium Alstoniae Scholaris are in cough-relieving with the synergism aspect relievining asthma.
Pharmacology test research
One, ammonia is caused the influence of mouse cough
Sample: Dy (with beta-cyclodextrin inclusion compound, Radix Angelicae Sinensis volatile oil is 1: 7 with the enclose ratio of cyclodextrin before the Radix Angelicae Sinensis oil, administration), Dt powder (the Folium Alstoniae Scholaris extract comprises water extract or ethanol extraction).
Laboratory animal: the ICR mice, the II level, ♀ ♂ half and half body weight 22～25g is provided credit number by Beijing Vital River Experimental Animals Technology Co., Ltd.: SCXX (capital) 2002-0003.
Reagent and equipment:
Carbetapentane citrate, the 25mg/ sheet, Tianjin Lisheng Pharmaceutical Co., Ltd. produces, lot number 0509016.After getting 1 tablet of carbetapentane citrate and putting into mortar and grind, add distilled water to 25ml, concentration is that 1mg/1ml is standby;
Ammonia, Tianjin chemical industry all generations company limited is produced, lot number: 030909;
The JWC-201D ultrasound atomizer, the Anshan produces with letter medical apparatus factory;
JOEREX (Zu Disi) the digital stopwatch that moves, Mesuca Development Co., Ltd in Guangzhou Free Trade Zone produces.
The route of administration of test sample and reference substance, dosage and grouping situation see the following form:
| Group | Number of animals (only) | Route of administration | Dosage (g/kg) |
| The blank group | 10 | Irritate stomach | Normal saline 20ml/kg |
| Carbetapentane citrate | 10 | Irritate stomach | 0.02 |
| The Dy high dose | 10 | Irritate stomach | 0.04 |
| Dosage among the Dy | 10 | Irritate stomach | 0.02 |
| The Dy low dosage | 10 | Irritate stomach | 0.01 |
| The Dt high dose | 10 | Irritate stomach | 0.5 |
| Dosage among the Dt | 10 | Irritate stomach | 0.25 |
| The De low dosage | 10 | Irritate stomach | 0.125 |
Experimental technique
80 of mices are divided into 8 groups at random.The blank group, positive (carbetapentane citrate) matched group, high, medium and low three dosage groups of Dy and high, medium and low three the dosage groups of Dt, dosage sees the above table.Each organizes after the mice administration 30 minutes, respectively mice (at every turn testing 2 mices) is put into the 500ml glass bell jar, 50ml strong aqua ammonia (25%) is placed the JWC-201D ultrasound atomizer, ultrasound atomizer links to each other with 500ml glass bell jar sprayer unit, (air door is adjusted in minimum, and the mist amount is regulated 7 grades).Start ultrasound atomizer, nebulisation time is 15 seconds, stops after 5 seconds rapidly mice to be taken out, and measures its cough latent period (mice draw the abdomen, raise, grab mouth magnify mouth simultaneously) then and the cough number of times of every mice in 2 minutes.Experimental data is done the T check with SPSS11.5 statistics software.The results are shown in Table 1:
The influence of table 1. pair ammonia initiation mouse cough (n=10, X ± SD)
| Group | Dosage (g/kg) | Cough latent period (S) | Cough number of times (inferior) |
| Dosage Dt low dosage among the dosage Dy low dosage Dt high dose Dt among the control group carbetapentane citrate Dy high dose Dy | -- 0.02 0.04 0.02 0.01 0.5 0.25 0.125 | 44.0±10.0 66.8±21.79 ** 48.3±9.5 47.2±8.3 47.4±11.5 63.0±11.0 ** 54.2±16.1 * 44.0±18.5 | 21.0±3.5 5.1±2.9 ** 15.7±5.3 18.3±4.9 17.9±6.2 8.8±1.7 ** 12.6±5.7 * 12.4±4.4 |
Annotate: compare with the blank group
*P＜0.01
*P＜0.05
Experimental result shows that Dy does not have obvious antitussive effect to the mouse cough that ammonia causes, and the mouse cough that Dt causes ammonia, can obviously reduce the cough number of times incubation period that can obviously prolong cough again, illustrate that Dt has tangible antitussive effect, high dose group has the effect of utmost point significance, P＜0.01.
Two, Dy, Dt cause Cavia porcellus to histamine phosphate and draw and breathe heavily preclinical influence
Experiment purpose: cause the method for breathing heavily with the histamine phosphate spraying, observe Dy, Dt to the Cavia porcellus antiasthmatic effect
Sample: Dy, Dt powder.
Experiment material:
Laboratory animal: Cavia porcellus, the I level, ♀ ♂ dual-purpose, body weight 150～200g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., credit number: SCXX (capital) 2002-0003.
Method and result:
Buy body weight 150～200g Cavia porcellus, the male and female dual-purpose, observed 24 hours, being as good as the elder is used for screening, being about to Cavia porcellus places in the airtight glass container that is connected with ultrasound atomizer, concentration is that the histamine phosphate of 2mg/ml atomizes through ultrasound atomizer, sprays in the glass container, and Cavia porcellus begins (to twitch, fall to symptom from spraying; Animal one is had a convulsion, and should take out from glass container immediately, in order to avoid death by suffocation.) time of occurring is incubation period, record incubation period.If surpass 150s, then will not select for use because of insensitive and superseded.Next day,, according to preclinical length, be divided into 7 groups at random, 10 every group with 70 Cavia porcelluss of incubation period in 150s.Grouping and dosage see the following form.
Animal grouping and route of administration and dosage
| Group | Number of animals (only) | Route of administration | Dosage (g/kg) |
| The blank group | 10 | Irritate stomach | Normal saline 20ml/kg |
| The Dy high dose | 10 | Irritate stomach | 0.04 |
| Dosage among the Dy | 10 | Irritate stomach | 0.02 |
| The Dy low dosage | 10 | Irritate stomach | 0.01 |
| The Dt high dose | 10 | Irritate stomach | 0.5 |
| Dosage among the Dt | 10 | Irritate stomach | 0.25 |
| The Dt low dosage | 10 | Irritate stomach | 0.125 |
Each treated animal is respectively by last table administration, 30min puts into the airtight glass container that is connected with ultrasound atomizer respectively after administration, the similarity condition concentration of spraying respectively is the histamine phosphate of 2mg/ml during by preliminary election, and record begins time of occurring to Cavia porcellus symptom (twitch, fall) from spraying.If 360s is the person that still do not keep one's legs, to draw and breathe heavily incubation period and calculate according to 360s, result of the test is t with the SPSS10.0 statistical software and is checked, and there was no significant difference is arranged between comparable group.The results are shown in Table 2.
Table 2 pair histamine phosphate causes Cavia porcellus and draws and breathe heavily preclinical influence (n=10, X ± SD)
| Group | Dosage (g/kg) | Draw and breathe heavily incubation period (S) |
| Dosage Dt low dosage among the dosage Dy low dosage Dt high dose Dt among the control group Dy high dose Dy | -- 0.04 0.02 0.01 0.5 0.25 0.125 | 104.0±37.8 360.0±0.0 ** 360.0±0.0 ** 224.4±62.3 * 111.3±27.8 126.4±36.3 142.4±58.5 |
Annotate: compare with the blank group
*P＜0.01
*P＜0.05
Experimental result shows, the Dy of 40mg/kg and 20mg/kg can the utmost point prolongs histamine phosphate significantly to be caused Cavia porcellus and draw and breathe heavily incubation period, P＜0.01, and 10mg/kgDy also can obviously prolong histamine phosphate and cause Cavia porcellus and draw and breathe heavily incubation period P＜0.05; Dt then draws to breathe heavily to histamine phosphate initiation Cavia porcellus does not have obvious effect incubation period.
Three, ammonia is caused mouse cough and histamine phosphate is caused Cavia porcellus draw and breathe heavily preclinical influence
Experiment purpose: cause the method for breathing heavily with the histamine phosphate spraying, observation Dy, Dt drug combination draw to ammonia initiation mouse cough with to histamine phosphate initiation Cavia porcellus breathes heavily preclinical influence.
Sample: Dy, Dt powder.
Experiment material is identical with experimental animal and afore-mentioned test.
Method and result:
Cough-relieving is all established four groups with the test of relievining asthma, and the cough-relieving result of the test sees Table 3a, the result of the test of the relievining asthma 3b that sees the following form.
Grouping and route of administration and dosage
| Group | Number of animals (only) | Route of administration | Dosage (g/kg) |
| The blank group | 10 | Irritate stomach | Normal saline 20ml/kg |
| The Dy+Dt group | 10 | Irritate stomach | Dy0.04+Dt0.5 |
| The Dy high dose group | 10 | Irritate stomach | 0.04 |
| The Dt high dose | 10 | Irritate stomach | 0.5 |
Table 3a. causes influence (n=10, the X ± SD) of mouse cough to ammonia
| Group | Dosage (g/kg) | Cough latent period (S) | Cough number of times (inferior) |
| Matched group Dy+Dt Dy high dose Dt high dose | -- 0.04+0.5 0.04 0.5 | 45.8±8.7 78.2±10.6 # ** 49.9±8.2 59.0±9.8.0 ** | 22.0±7.5 5.9±2.9 # ** 15.4±7.1 9.7±2.6 ** |
Annotate: compare with the blank group
*P＜0.01
*#P＜0.05 is compared with the Dt group in P＜0.05
Table 3b. causes Cavia porcellus to histamine phosphate and draws and breathe heavily preclinical influence (n=10, X ± SD)
| Group | Dosage (g/kg) | Draw and breathe heavily incubation period (S) |
| Matched group Dy+Dt Dy high dose Dt high dose | -- 0.04+0.5 0.04 0.5 | 104.0±37.8 531.0±30.5 # ** 384.0±28.5 ** 123.6±19.2 |
Annotate: compare with the blank group
*P＜0.01
*P＜0.05; Compare #P＜0.05 with the Dy high dose group
Four, the affirmation of Dy and Dt optimal proportion
Laboratory animal test material and method are the same.
Test grouping: with Dy: Dt be 1: 13 be the center, established respectively 1: 5; 1: 10,1: 15; 1: 20 four dosage group and comparing at 1: 13; The results are shown in Table 4 and table 5, wherein Dt is the Folium Alstoniae Scholaris water extract.
The Dy of table 4 different proportion, Dt cause influence (n=10, the X ± SD) of mouse cough to ammonia
| Group | Dosage (g/kg) | Cough latent period (S) | Cough number of times (inferior) |
| Matched group Dy: Dt=1: 5 Dy: Dt=1: 10 Dy: Dt=1: 13 Dy: Dt=1: 15 Dy: Dt=1: 20 | -- 0.04+0.2 0.04+04 0.04+0.5 0.04+0.6 0.04+0.8 | 40.2±11.5 60.2±13.6 * 69.9±10.2 * 76.6±10.5.0 ** 75.4±12.6 ** 79.3±13.1 ** | 25.3±5.6 15.9±2.9 * 15.4±7.1 * 9.7±2.6 ** 11.6±5.6 ** 12.7±4.1 ** |
Annotate: compare with the blank group
*P＜0.01
*P＜0.05
The ratio of Dt increases as seen from Table 4, and cough latent period prolongs, the cough number of times reduces, but with 1: 13 group relatively and not obvious, 1: 15; 1: 20 dosage increase effect not as good as or not obviously be better than 1: 13 group, show for antitussive action the part by weight of Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris water extract most preferably 1: 13.
For the Folium Alstoniae Scholaris ethanol extraction repeats above-mentioned experiment, obtain the part by weight preferred 1 of Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris ethanol extraction: the optimal proportion of 4-5 with Dt.
Table 5 pair histamine phosphate causes Cavia porcellus and draws and breathe heavily preclinical influence (n=10, X ± SD)
| Group (Dy: Dt) | Dosage (g/kg) | Draw and breathe heavily incubation period (S) |
| Matched group 1: 51: 10 1: 13 1: 15 1: 20 | -- 0.04+0.2 0.04+04 0.04+0.5 0.04+0.6 0.04+0.8 | 104.0±37.8 331.0±26.3 ** 384.0±28.5 ** 548.9±32.6 ** 406.6±34.7 ** 394.2±38.6 ** |
Annotate: compare with the blank group
*P＜0.01
As seen from Table 5 the change of the ratio of Dt with draw that to breathe heavily preclinical variation uncorrelated, with 1: 13 group relatively 1: 5; 1: 10; 1: 15; 1: 20 effect shows as Dy not as good as 1: 13 group: when Dt is 1: 13 for the antiasthmatic effect best results.
In sum, unite use Dy and Dt, the weight ratio of Dy: Dt 1: 13rd, optimal proportion.
The high dose group dosage of Dy and Dt is mixed, obtain unexpected cough-relieving and antiasthmatic effect, illustrate that it is not simple curative effect summation action but collaborative potentiation that The combined is used, make up its pharmacological action and effect obviously not as the effect and the effect of the combination of Dy and Dt from simple Radix Angelicae Sinensis volatile oil (or Folium Alstoniae Scholaris extract) and other Chinese medicine extract, can prove synergism of the present invention from another angle with antiasthmatic effect.
Five, the Cavia porcellus experiment of relievining asthma:
With 2% acecoline and 0.1% histamine phosphate mixed liquor, bring out clear-headed Cavia porcellus asthma.Get 1 of Cavia porcellus at every turn, put in the airtight glass bell jar of 4L, in airtight bell jar, feed 2% acecoline and 0.1% histamine phosphate mixed liquor (1: the 1) 10s of atomizing with the capacity of 0.5ml/min with ultrasonic atomization, observe the asthma incubation period (generally be no more than 120s, otherwise be considered as insensitive will not selecting for use) of Cavia porcellus.
1, gastric infusion once, administration group and blank group no significant difference.
2, continuously behind the gastric infusion four days (once a day), observe, the results are shown in Table 6.
Table 6. present composition is to the antiasthmatic effect of Cavia porcellus
| Group | Asthma incubation period (S) | Prolong behind the medicine | |
| Before the administration (average) | After the administration (average) | ||
| Matched group (giving the equivalent solvent) | |||
| 1 | 62 | 71 | 9 |
| 2 | 76 | 68 | -8 |
| 3 | 68 | 67 | -1 |
| 4 | 60 | 71 | 11 |
| 5 | 71 | 75 | 4 |
| The administration group | |||
| 1 | 63 | 210 | 147 |
| 2 | 77 | 125 | 48 |
| 3 | 69 | 310 | 241 |
| 4 | 59 | 119 | 60 |
| 5 | 65 | 179 | 144 |
The result shows that this prescription has significant inhibitory effect to the Cavia porcellus asthma due to the histamine.
Six, mice cough-relieving experiment
Method: gastric infusion is once observed cough latent period and cough number of times, sees Table 7.
Table 7. is breathed with cough and is put down the antitussive action that No. 1 strong aqua ammonia is caused mouse cough
| Group | Incubation period (s) | P | Cough (inferior) | P |
| The normal control group | 34.0±10.0 | 21.0±3.5 | ||
| Low dose group | 63.0±11.0 | 0.002 | 4.4±1.7 | 0.000 |
| Middle dosage group | 54.2±26.1 | 0.166 | 8.6±5.7 | 0.003 |
| High dose group | 64.0±18.5 | 0.012 | 10.2±4.4 | 0.003 |
The result: this prescription has significant inhibitory effect to the mouse cough that strong aqua ammonia causes.
Conclusion: the present composition is a compound Chinese medicinal preparation, the clinical cough, asthma that is used for the treatment of, determined curative effect.
In sum, the present composition is better than medicine commonly used at present to the treatment improvement effect of cough, asthma, especially after the treatment of carrying out a course of treatment (five days), there is positive effect to improve to asthma, also is better than heavy dose of Radix Angelicae Sinensis volatile oil and the independent medication of Folium Alstoniae Scholaris extract.The result of test shows determined curative effect, and is safe and effective, and long-time stability are investigated and also shown, present composition steady quality, reliable.
Toxicology test
The pure Radix Angelicae Sinensis volatile oil (be to adopt beta-cyclodextrin inclusion compound during application, Radix Angelicae Sinensis volatile oil is 1: 7 with the enclose ratio of cyclodextrin) of dy representative among the present invention; Dt represents the Folium Alstoniae Scholaris extract.
1. acute toxicity test
1.1 sample: the product of the embodiment of the invention 1 (being called for short Dy+Dt), brown ceramic powder is slightly soluble in water.
1.2 laboratory animal: II level ICR mice, male and female half and half, body weight 16～18g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., credit number SCXK (capital) 2002-001.
Animal feeding in IVC, 20～23 ℃ of temperature, relative humidity 50～60%, free drinking pure water, picked-up standard feed, laboratory animal occupancy permit numbering: syxk (Tianjin) 2005-0001.
1.3 dosage design: through giving examination, 30g/kg is dead entirely, 20g/kg dead half, so design 30g/kg is a maximal dose, between agent than being that 0.8, five dosage is 30.00,24.00,19.20,15.36 respectively, 12.29g/kg.
1.4 method and result: buy 50 of ICR mices, male and female half and half, body weight 16～18g observed 2 days, and no abnormality seen is divided into 5 groups, each 5 of every group of male and female.With 12h before the administration, stop eating and do not cut off the water.
With 2% carboxymethyl cellulose is solvent, and the 45g sample adds solvent to 60ml, mixing, and 30g/40ml/kg then, i.e. 0.8ml/20g, this solution is called solution I.Get I liquid 48ml, add solvent to 60ml, solution II, 24g/40ml/kg then, by that analogy, solution III, IV, V, be respectively 19.20,15.36 and 12.29g/40ml/kg.12h before the administration stops eating and does not cut off the water.Five groups of mices give solution I, IIIII, IV and V, observation death condition respectively, continuous 7 days.The dead mouse details is owed to give temporarily after the administration.
Calculate median lethal dose(LD 50) with the Bliss method:
LD50＝18.715g/kg
Fiducial limit=15.539--22.278g/kg of LD50 (Feiller correction) 95%
LD5＝9.8013g/kg
LD95＝35.735g/kg
2. long term toxicity (13 weeks, rat) test
2.1 laboratory animal: the Wistar rat, the II level, body weight 100 ± 10 grams, male and female half and half are provided by Beijing Vital River Experimental Animals Technology Co., Ltd..Licence numbering SCXK (capital) 2002-0003.
2.2 reagent
Eight joint-trial paper, Gao Erbao Bioisystech Co., Ltd produces, lot number 20050902
Test kit, Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd. produces
2.3 test method
2.3.1 dosage design
The pharmacodynamics test high dose of Dy+Dt is 0.54g/kg.LD
50Establishing 1g/kg for the 18.7g/kg. event is low dosage, and 2g/kg is middle dosage, and 4g/kg is a high dose.Long term toxicity test low dose group dosage is higher than pharmacodynamics test high dose group dosage (1g/kg＞0.54g/kg), and long term toxicity test high dose group dosage 4g/kg is LD
5018.7g/kg 1/4.7.
2.3.2 long malicious dosage group is set:
The Cmax that can pass through with the rat oral gavage pin is as the high dose of long term toxication, with its 1/2 dosage as in dosage, during low dosage is made as 1/2 of dosage.Rat is divided into 4 groups, 20 every group, each 10 of male and female.Be respectively high, normal, basic three the dosage groups of normal control group and Dy+Dt.The normal control group is irritated stomach with drinking water 20ml/kg per os every day; Dy+Dt is with 4g/kg, 2g/kg, 1g/kg (be equivalent to LD50[18.715g/kg] 1/4.7,1/9.4 and 1/18.8), and every day, per os was irritated stomach, and administration is 6 days weekly, continuous 13 weeks.Do the ordinary circumstance observation every day during the administration, weighs weekly once to adjust dosage; Measure average food ration weekly 1 time; And respectively at doing routine urinalysis (mensuration is occulted blood, nitrite, PH, urobilinogen, bilirubin, protein, glucose, ketoboidies, estimates eight joint-trial agent band methods) after 13 weeks of administration and 4 weeks of drug withdrawal; Hematology's (measuring leukocyte count, RBC number, hemoglobin, platelet count, lymphocyte percentage ratio, neutrophilic granulocyte percentage ratio and clotting time); Blood biochemical is learned (detection of alkaline phosphatase, glutamate pyruvate transaminase, glutamic oxaloacetic transaminase, GOT, total protein, albumin, blood urea nitrogen, flesh liver, total bilirubin, blood glucose and T-CHOL); And in 13 14 of all dissections and 6 rats of 4 week of drug withdrawal back dissection, core, liver, spleen, lung, kidney, brain, thyroid, adrenal gland, testis, prostate or uterus weigh, calculate organ coefficient, win hypophysis, optic nerve, stomach, pancreas, duodenum, backlash intestinal, bladder, epididymis, thymus, lymph node, bone marrow, ovary or epididymis in addition, carry out histopathologic examination together with the above-mentioned internal organs of weighing.More than every index there is no unusually, three dosage groups and normal control group relatively, there was no significant difference, P＞0.05.
Result of the test shows, continuous 13 weeks of LD50/4.7 to irritate stomach to rat oral, does not see that Dy+Dt has overt toxicity.Long malicious test dose of animal and pharmacodynamics test consumption convert and see Table 8.
Long malicious test dose of table 8. animal and pharmacodynamics test consumption convert
| The dosage group | Be equivalent to LD 50Multiple | Be equivalent to effect experiment high dose multiple |
| High dose: 4g/kg/20ml | 1/4.7 | 7.4 |
| Middle dosage: 2g/kg/20ml | 1/9.4 | 3.7 |
| Low dosage: 1g/kg/20ml | 1/18.8 | 1.85 |
2.4 observation index:
2.4.1 general situation is observed: observe general symptom, behavior, mouth and nose secretions, the defecation situation of animal before and after administration every day and have or not other unusual, if any unusual timely itemized record.
2.4.2 body weight situation: give after animal is bought and raising three days, after the body weight grouping, measure the preceding body weight of every group of administration.After the beginning administration, measure body weight weekly 1 time.
2.4.3 food ration: measure weekly 1 time.
2.4.4 uroscopy: when being administered to for 13 weeks, get 14 animals for every group; When convalescent period finishes, get 6 animals for every group, single only being placed on collected urine in the metabolic cage, measure occult blood, nitrite, PH, urobilinogen, bilirubin, protein, glucose, ketoboidies (estimating eight joint-trial agent band methods).
2.4.5 hematological examination: be administered to when finishing in 13 weeks and convalescent period when finishing, under etherization, get blood after 1 night of animal fasting from the puncture of eye socket rear vein beard.Measure: leukocyte count (WBC), RBC number (RBC), hemoglobin concentration (HGB), platelet count (PLT), lymphocyte percentage ratio (W-SCR), neutrophilic granulocyte percentage ratio (W-LCR) and clotting time, determining instrument: Sysmex F-820 auto-counter, TOA Medicalelectronics Co., Ltd. Japan.Measure clotting time with slide method simultaneously.
2.4.6 blood biochemical learn to be checked: be administered to when finishing in 13 weeks and convalescent period when finishing, after 1 night of animal fasting, under etherization get blood through femoral vein, leave standstill back 3000rpm, centrifugal 10min gets serum and carries out the biochemical indicator detection: alkali phosphatase (ALP, the PNPP method), glutamate pyruvate transaminase (ALT, enzyme performance rate method), glutamic oxaloacetic transaminase, GOT (AST, enzyme performance rate method), total protein (T-PRO, biuret method), albumin (ALB, bromocresol green method), blood urea nitrogen (BWN, diacetyl-oxime method), flesh liver (CREAT, picric acid method), total bilirubin (BILI, the diazonium method), blood glucose (GLU, glucose oxidase method), T-CHOL (CHOL, enzyme process).
2.4.7 dissect and histological examination: when 13 weeks finished after the administration and convalescent period when finishing, animal is in dissecting the fasting in eve, when dissected is femoral artery sacrificed by exsanguination animal under etherization, after the perusal, core, liver, spleen, lung, kidney, brain, thyroid, adrenal gland, testis, prostate or uterus weigh, calculate organ coefficient, win hypophysis, optic nerve, stomach, pancreas, duodenum, backlash intestinal, bladder, epididymis, thymus, lymph node, bone marrow, ovary or epididymis in addition, carry out histopathologic examination together with the above-mentioned internal organs of weighing.Above-mentioned internal organs are through the fixed specimen of respectively organizing of 10% formalin solution, and the ethanol gradient was dewatered after routine was drawn materials, the embedding of the automatic paraffin embedding machine of Fisher Model 266MP, and the film-making of Leica RM2135 microtome, HE dyeing, the OLYMPUS microscopic examination is taken a picture.
3. result of the test
3.1 general situation is observed: the general symptom of observing animal before and after administration every day.Do not see mouth and nose secretions, loose stool, do not see dystropy.
3.2 body weight situation: after the body weight grouping, measure the preceding body weight of every group of administration.After the beginning administration, measure body weight weekly 1 time.The visible same time of result, compare there was no significant difference, P＞0.05 between each administration group and the comparison of normal control group and each administration group.
3.3 food ration: measure weekly 1 time, the result as seen, average every the rat of different groups, identical time, identical sex consumes the feedstuff no significant difference weekly.
3.4 uroscopy: every routine urinalysis no significant difference between the visible Dy+Dt long term toxicity test of result administration 13 all each administration groups and the comparison of normal control group and each administration group.
3.5 hematological examination: every routine blood test no significant difference between the visible Dy+Dt long term toxicity test of result administration 13 all each administration groups and the comparison of normal control group and each administration group, P＞0.05.
3.6 learning, blood biochemical checks: every blood parameters no significant difference between the visible Dy+Dt long term toxicity test of result administration 13 all each administration groups and the comparison of normal control group and each administration group, P＞0.05.
3.7 dissect and histological examination, after 13 weeks of administration and 4 weeks of drug withdrawal, when dissected, perusal, no abnormality seen, organ coefficient no significant difference, P＞0.05.
The specific embodiment
For more clear explanation goal of the invention and technical scheme, be described in further detail by following embodiment.
Embodiment 1:
The prescription of compositions of the present invention:
Radix Angelicae Sinensis volatile oil 7%; Folium Alstoniae Scholaris extract 93%.The compositions gross weight of forming in Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris extract is 100%.
The extraction of Radix Angelicae Sinensis volatile oil: get the Radix Angelicae Sinensis medical material, adopt distillatory method preparation, get Radix Angelicae Sinensis volatile oil;
The extraction of Folium Alstoniae Scholaris extract: get the Folium Alstoniae Scholaris medical material, add 95% alcohol reflux 2 times, each 2 hours, filter merging filtrate, reclaim ethanol to a certain amount of, add 2 times of water gagings, stir, placed 24 hours, filter, filtrate concentrates, and is spray dried to powder, gets the Folium Alstoniae Scholaris extract;
Above-mentioned Radix Angelicae Sinensis volatile oil that obtains and Folium Alstoniae Scholaris extract are mixed, the encapsulating capsule, promptly.
Also can adopt conventional inclusion technique enclose to make volatile oil clathrate compound Radix Angelicae Sinensis volatile oil and beta-schardinger dextrin-, wherein the part by weight of volatile oil and beta-schardinger dextrin-be 1: 5, mixes with the Folium Alstoniae Scholaris extract again, promptly gets the capsule of the present composition.In the compositions gross weight is 100%, and the Radix Angelicae Sinensis volatile oil clathrate is 7-35%; Folium Alstoniae Scholaris extract 65-93%.
Differentiate: (1) gets this product 1g, puts in the 100ml measuring bottle, adds Diluted Alcohol 10ml, and reflux 30 minutes is put coldly, filters, and filtrate is as need testing solution.Other gets the Folium Alstoniae Scholaris control medicinal material, get control medicinal material solution with legal system, test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 5 μ l of above-mentioned two kinds of solution respectively, the point in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with ethyl acetate-butanone-formic acid-water (5: 3: 1: 1) be developing solvent, launch, take out, dry, spray is with 1% aluminum chloride alcoholic solution, put under the ultra-violet lamp (365nm) and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
(2) get discriminating (a 1) following need testing solution as need testing solution; Get discriminating (1) item control medicinal material solution 1ml down, add Diluted Alcohol to be diluted to 3ml, in contrast medical material solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 10 μ l of above-mentioned two kinds of solution respectively, point is on same silica gel g thin-layer plate, with ethyl acetate-acetone-ethanol-acetic acid-water (1: 1: 8: 1: 0.5) is developing solvent, launch, take out, dry, spray is with improvement bismuth potassium iodide solution.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
(3) get this product 1g, the 20ml supersound extraction that adds diethyl ether 10 minutes is filtered, and extracting solution is concentrated into 1ml, as need testing solution; Get Radix Angelicae Sinensis control medicinal material 0.5g, shine medical material solution in pairs with legal system.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 10 μ l of above-mentioned two kinds of solution respectively, point is developing solvent with normal hexane-ethyl acetate (9: 1) on same silica gel g thin-layer plate, launches, take out, dry, put under the ultra-violet lamp (365nm) and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical light blue white fluorescent speckle.
Check: present composition granule meets the relevant every regulation (appendix IC of Chinese Pharmacopoeia version in 2000) under the granule item.
Assay:
Ligustilide adopts gas chromatography (appendix of Chinese Pharmacopoeia version in 2005) to measure.
Chromatographic condition: with octadecylsilane chemically bonded silica is filler; Methanol-1.2% acetic acid (55: 45) is mobile phase, and the detection wavelength is 280nm.
The preparation of reference substance solution: it is an amount of to get the ligustilide reference substance, and accurate the title decides, and adds methanol and makes the solution that every ml contains 0.25mg, promptly.
The preparation of need testing solution: get the product content thing 1g of embodiment 1, the accurate title, decide, and puts in the 25ml measuring bottle, adds an amount of supersound process of methanol 20 minutes, and be centrifugal, filters, promptly.
Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly.The content of ligustilide is about 5.7mg/g in the above-mentioned composition of the present invention.
Indoles alkaloid, adopt titrimetry:
Precision takes by weighing this product (compositions of the embodiment of the invention 1) fine powder 5g, puts in the 250ml conical flask, adds 95% ethanol 80ml, reflux 1 hour, put coldly, filter, residue adds 95% ethanol 80ml again, reflux 0.5 hour, put coldly, filter merging filtrate, evaporate to dryness.Residue adds hydrochloric acid solution (1 → 100) 30ml, puts in the water-bath and heats, and stirs and makes dissolving, put cold, filter, residue reuse hydrochloric acid solution (1 → 200) with method extract 2 times (20ml, 15ml), merging filtrate, regulate pH value to 8～8.5 with ammonia solution, extract 4 (40ml, 30ml with the chloroform jolting, 25ml, 20ml), combined chloroform liquid, water jolting washing is to neutral, move in the 100ml conical flask, reclaim solvent to doing, accurate sulphuric acid volumetric solution (0.005mol/l) 25ml that adds makes dissolving, puts cold, 2 of the red indicator solutions of methylate are with sodium hydroxide volumetric solution (0.01mol/l) titration.Every 1ml sulphuric acid volumetric solution (0.005mol/l) is equivalent to the picrinine (C of 3.384mg
20H
22N
2O
3).
This product contains indoles alkaloid with picrinine (C
20H
22N
2O
3) meter, contain 20～500 μ g/g.
The assay of picrinine: high performance liquid chromatography (Chinese Pharmacopoeia version (an one) in 2005 appendix VID) is measured.
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica (Xterra), aqueous hydrochloric acid solution (concentrated hydrochloric acid 1 → 100)-acetonitrile (80: 20) is a mobile phase, the detection wavelength is 232nm, and theoretical cam curve is calculated by picrinine should be not less than 7000.
It is an amount of that the picrinine reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds the acetonitrile dissolving and make the solution that every 1ml contains 50 μ g.
The preparation of need testing solution is got this product and is ground, and the accurate powder 1.50g that claims puts in the 200ml conical flask, add the ammonia test solution (2% strong aqua ammonia, PH=9) 100ml extracts 2 times, filters, filtrate is used chloroform extraction 3 times, each 100ml, combining extraction liquid, water jolting washing is reclaimed solvent to doing to neutral, with acetonitrile precipitation is transferred to the 25ml volumetric flask, add acetonitrile to scale, shake up, filter, filtrate is as need testing solution.
Algoscopy is got 10 μ l reference substance solution and each 10 μ l of need testing solution respectively, injects chromatograph of liquid, and the record chromatogram is pressed external standard method with calculated by peak area, promptly.
Every of the present composition (capsule, content 0.4g) contains picrinine and must not be lower than 20 μ g, contains ligustilide and is not less than 10mg.
Embodiment 2:
Prescription: Radix Angelicae Sinensis volatile oil 25%; Folium Alstoniae Scholaris extract 75%.The compositions gross weight of forming in Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris extract is 100%.
Tablet: (1) gets the Radix Angelicae Sinensis medical material, adopts the method preparation of carbon dioxide supercritical fluid extraction, gets Radix Angelicae Sinensis volatile oil;
(2) get the Folium Alstoniae Scholaris medical material, decoct with water 2 times, each 2 hours, collecting decoction filtered, and filtrate is concentrated into relative density 1.3, added ethanol to containing alcohol amount 65%, left standstill 24 hours, got supernatant and reclaimed ethanol, was spray dried to powder, got the Folium Alstoniae Scholaris extract;
(3) extract that above-mentioned (1) and (2) is obtained mixes;
(4) additive of tablet of adding routine dose and kind, tabletting promptly obtains tablet of the present invention.
Capsule: the blended step of said extracted thing (3) adds binding agents such as dextrin afterwards, and fully mixing adds filler granulations such as starch, and is encapsulated, promptly gets capsule of the present invention, and wherein binding agent and filler etc. are the conventional adjuvant of the conventional ratio of capsule.
Qualitative and detection by quantitative is with embodiment 1.
The assay of picrinine: high performance liquid chromatography (Chinese Pharmacopoeia version (an one) in 2005 appendix VID) is measured.
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica (Xterra), aqueous hydrochloric acid solution (concentrated hydrochloric acid 1 → 100)-acetonitrile (80: 20) is a mobile phase, the detection wavelength is 232nm, and theoretical cam curve is calculated by picrinine should be not less than 7000.
It is an amount of that the picrinine reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds the acetonitrile dissolving and make the solution that every 1ml contains 50 μ g.
The preparation of need testing solution is got this product and is ground, and the accurate powder 1.50g that claims puts in the 200ml conical flask, add the ammonia test solution (2% strong aqua ammonia, PH=9) 100ml extracts 2 times, filters, filtrate is used chloroform extraction 3 times, each 100ml, combining extraction liquid, water jolting washing is reclaimed solvent to doing to neutral, with acetonitrile precipitation is transferred to the 25ml volumetric flask, add acetonitrile to scale, shake up, filter, filtrate is as need testing solution.
Algoscopy is got 10 μ l reference substance solution and each 10 μ l of need testing solution respectively, injects chromatograph of liquid, and the record chromatogram is pressed external standard method with calculated by peak area, promptly.
The present composition (tablet, every 0.2g) contains picrinine and is not less than 20 μ g, and ligustilide is not less than 10mg.
Embodiment 3:
Prescription: Radix Angelicae Sinensis volatile oil 5%; Folium Alstoniae Scholaris extract 95%.The compositions gross weight of forming in Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris extract is 100%.
Tablet: (1) gets the Radix Angelicae Sinensis medical material, adopts the method preparation of vapor distillation, gets Radix Angelicae Sinensis volatile oil;
(2) get the Folium Alstoniae Scholaris medical material, add 75% alcohol reflux 2 times, each 2 hours, filter, merging filtrate, recovery ethanol adds 2 times of water gagings to a certain amount of, stirs, and places 24 hours, filters, and filtrate concentrates, and is spray dried to powder, gets the Folium Alstoniae Scholaris extract;
(3) extract that above-mentioned (1) and (2) is obtained mixes;
(4) add conventional additive of tablet, tabletting.
Capsule: the blended step of said extracted thing (3) adds filleies such as starch afterwards, adds the abundant mixings of binding agent such as dextrin, granulates, and is encapsulated, promptly gets capsule of the present invention.
Qualitative and detection by quantitative is with embodiment 1.
The assay of picrinine: high performance liquid chromatography (Chinese Pharmacopoeia version (an one) in 2005 appendix VID) is measured.
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica (Xterra), aqueous hydrochloric acid solution (concentrated hydrochloric acid 1 → 100)-acetonitrile (80: 20) is a mobile phase, the detection wavelength is 232nm, and theoretical cam curve is calculated by picrinine should be not less than 7000.
It is an amount of that the picrinine reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds the acetonitrile dissolving and make the solution that every 1ml contains 50 μ g.
The preparation of need testing solution is got this product and is ground, and the accurate powder 1.50g that claims puts in the 200ml conical flask, add the ammonia test solution (2% strong aqua ammonia, PH=9) 100ml extracts 2 times, filters, filtrate is used chloroform extraction 3 times, each 100ml, combining extraction liquid, water jolting washing is reclaimed solvent to doing to neutral, with acetonitrile precipitation is transferred to the 25ml volumetric flask, add acetonitrile to scale, shake up, filter, filtrate is as need testing solution.
Algoscopy is got 10 μ l reference substance solution and each 10 μ l of need testing solution respectively, injects chromatograph of liquid, and the record chromatogram is pressed external standard method with calculated by peak area, promptly.
The present composition (capsule, the tolerant 0.27g of every intragranular) contains picrinine and must not be lower than 20 μ g.
Embodiment 4:
Prescription: Radix Angelicae Sinensis volatile oil 5%; Folium Alstoniae Scholaris extract 95%.The compositions gross weight of forming in Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris extract is 100%.
Tablet: (1) gets the Radix Angelicae Sinensis medical material, adopts the method preparation of vapor distillation, gets Radix Angelicae Sinensis volatile oil;
(2) get the Folium Alstoniae Scholaris medical material, add 60% alcohol reflux 2 times, each 2 hours, filter, merging filtrate reclaims ethanol to a certain amount of, concentrates, and is spray dried to powder, gets the Folium Alstoniae Scholaris extract;
(3) extract that above-mentioned (1) and (2) is obtained mixes;
(4) add conventional additive of tablet, tabletting.
Capsule: the blended step of said extracted thing (3) adds filleies such as starch afterwards, adds binding agents such as dextrin, and fully mixed pelletization is encapsulated, promptly gets capsule of the present invention.
Qualitative and detection by quantitative is with embodiment 1.
The assay of picrinine: high performance liquid chromatography (Chinese Pharmacopoeia version (an one) in 2005 appendix VID) is measured.
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica (Xterra), aqueous hydrochloric acid solution (concentrated hydrochloric acid 1 → 100)-acetonitrile (80: 20) is a mobile phase, the detection wavelength is 232nm, and theoretical cam curve is calculated by picrinine should be not less than 7000.
It is an amount of that the picrinine reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds the acetonitrile dissolving and make the solution that every 1ml contains 50 μ g.
The preparation of need testing solution is got this product and is ground, and the accurate powder 1.50g that claims puts in the 200ml conical flask, add the ammonia test solution (2% strong aqua ammonia, PH=9) 100ml extracts 2 times, filters, filtrate is used chloroform extraction 3 times, each 100ml, combining extraction liquid, water jolting washing is reclaimed solvent to doing to neutral, with acetonitrile precipitation is transferred to the 25ml volumetric flask, add acetonitrile to scale, shake up, filter, filtrate is as need testing solution.
Algoscopy is got 10 μ l reference substance solution and each 10 μ l of need testing solution respectively, injects chromatograph of liquid, and the record chromatogram is pressed external standard method with calculated by peak area, promptly.
The present composition (capsule, the tolerant 0.27g of every intragranular) contains picrinine and must not be lower than 20 μ g.
Embodiment 5:
Prescription: Radix Angelicae Sinensis volatile oil 90%; Folium Alstoniae Scholaris extract 10%.The compositions gross weight of forming in Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris extract is 100%.
Tablet: (1) gets the Radix Angelicae Sinensis medical material, adopts the method preparation of vapor distillation, gets Radix Angelicae Sinensis volatile oil;
(2) get the Folium Alstoniae Scholaris medical material, add alcohol reflux 2 times, each 2 hours, filter, merging filtrate reclaims ethanol to a certain amount of, adds 2 times of water gagings, stir, placed 24 hours, and filtered, filtrate is concentrated into the extractum of relative density 1.05～1.08, transfer pH to 3-4 with hydrochloric acid, filter, supernatant is crossed 732 type cation exchange resin columns, with 10 times of volume water washings, discard cleaning mixture, with 1 times of column volume strong aqua ammonia alkalization post,, collect eluent with 6 times of volume 30～50% ethanol elutions, pressurization concentrates and cold drying, Folium Alstoniae Scholaris extract (picrinine content should greater than 80%);
(3) extract that above-mentioned (1) clathrate and (2) are obtained mixes;
(4) add conventional additive of tablet, tabletting.
Capsule: the blended step of said extracted thing (3) adds filleies such as starch afterwards, adds binding agents such as dextrin, and fully mixed pelletization is encapsulated, promptly gets capsule of the present invention.
Qualitative and detection by quantitative is with embodiment 1.
The assay of picrinine: high performance liquid chromatography (Chinese Pharmacopoeia version (an one) in 2005 appendix VID) is measured.
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica (Xterra), aqueous hydrochloric acid solution (concentrated hydrochloric acid 1 → 100)-acetonitrile (80: 20) is a mobile phase, the detection wavelength is 232nm, and theoretical cam curve is calculated by picrinine should be not less than 7000.
It is an amount of that the picrinine reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds the acetonitrile dissolving and make the solution that every 1ml contains 50 μ g.
The preparation of need testing solution is got this product and is ground, and the accurate powder 1.50g that claims puts in the 200ml conical flask, add the ammonia test solution (2% strong aqua ammonia, PH=9) 100ml extracts 2 times, filters, filtrate is used chloroform extraction 3 times, each 100ml, combining extraction liquid, water jolting washing is reclaimed solvent to doing to neutral, with acetonitrile precipitation is transferred to the 25ml volumetric flask, add acetonitrile to scale, shake up, filter, filtrate is as need testing solution.
Algoscopy is got 10 μ l reference substance solution and each 10 μ l of need testing solution respectively, injects chromatograph of liquid, and the record chromatogram is pressed external standard method with calculated by peak area, promptly.
The present composition (capsule, the tolerant 0.27g of every intragranular) contains picrinine and is not less than 20 μ g.
Embodiment 6:
Prescription: Radix Angelicae Sinensis volatile oil 80%; Folium Alstoniae Scholaris extract 20%.The compositions gross weight of forming in Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris extract is 100%.
Tablet: (1) gets the Radix Angelicae Sinensis medical material, adopts the method preparation of vapor distillation, gets Radix Angelicae Sinensis volatile oil;
(2) get the Folium Alstoniae Scholaris medical material, add alcohol reflux 2 times, each 2 hours, filter, merging filtrate reclaims ethanol to a certain amount of, add 2 times of water gagings, stir, placed 24 hours, filter, filtrate is concentrated into the extractum of relative density 1.05～1.08, puts 60～80 ℃ of vacuum dryings, pulverize, last preparation of silica gel post is with chloroform-methanol (20: 1) eluting, collect eluent, reclaim solvent, get Folium Alstoniae Scholaris extract (picrinine content is greater than 80%);
(3) extract that above-mentioned (1) clathrate and (2) are obtained mixes;
(4) add conventional additive of tablet, tabletting.
Capsule: the blended step of said extracted thing (3) adds filleies such as starch afterwards, adds binding agents such as dextrin, and fully mixed pelletization is encapsulated, promptly gets capsule of the present invention.
Qualitative and detection by quantitative is with embodiment 1.
The assay of picrinine: high performance liquid chromatography (Chinese Pharmacopoeia version (an one) in 2005 appendix VID) is measured.
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica (Xterra), aqueous hydrochloric acid solution (concentrated hydrochloric acid 1 → 100)-acetonitrile (80: 20) is a mobile phase, the detection wavelength is 232nm, and theoretical cam curve is calculated by picrinine should be not less than 7000.
It is an amount of that the picrinine reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds the acetonitrile dissolving and make the solution that every 1ml contains 50 μ g.
The preparation of need testing solution is got this product and is ground, and the accurate powder 1.50g that claims puts in the 200ml conical flask, add the ammonia test solution (2% strong aqua ammonia, PH=9) 100ml extracts 2 times, filters, filtrate is used chloroform extraction 3 times, each 100ml, combining extraction liquid, water jolting washing is reclaimed solvent to doing to neutral, with acetonitrile precipitation is transferred to the 25ml volumetric flask, add acetonitrile to scale, shake up, filter, filtrate is as need testing solution.
Algoscopy is got 10 μ l reference substance solution and each 10 μ l of need testing solution respectively, injects chromatograph of liquid, and the record chromatogram is pressed external standard method with calculated by peak area, promptly.
The present composition (capsule, the tolerant 0.27g of every intragranular) contains picrinine and is not less than 20 μ g.
Embodiment 7:
Prescription: Radix Angelicae Sinensis volatile oil 70%; Folium Alstoniae Scholaris extract 30%.The compositions gross weight of forming in Radix Angelicae Sinensis volatile oil and Folium Alstoniae Scholaris extract is 100%.
Tablet: (1) gets the Radix Angelicae Sinensis medical material, adopts the method preparation of vapor distillation, gets Radix Angelicae Sinensis volatile oil;
(2) get the Folium Alstoniae Scholaris medical material, add alcohol reflux 2 times, each 2 hours, filter, merging filtrate reclaims ethanol to a certain amount of, adds 2 times of water gagings, stirs, placed 24 hours, and filtered, filtrate is concentrated into does not have the alcohol flavor, last D101 macroporous adsorbent resin with 10 times of volume water washings, discards cleaning mixture, reuse 10% washing with alcohol discards cleaning mixture, reuse 90% ethanol elution, collect eluent, pressurization concentrates and cold drying, gets Folium Alstoniae Scholaris extract (picrinine content is greater than 50%);
(3) extract that above-mentioned (1) clathrate and (2) are obtained mixes;
(4) add conventional additive of tablet, tabletting.
Capsule: the blended step of said extracted thing (3) adds filleies such as starch afterwards, adds binding agents such as dextrin, and fully mixed pelletization is encapsulated, promptly gets capsule of the present invention.
Qualitative and detection by quantitative is with embodiment 1.
The assay of picrinine: high performance liquid chromatography (Chinese Pharmacopoeia version (an one) in 2005 appendix VID) is measured.
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica (Xterra), aqueous hydrochloric acid solution (concentrated hydrochloric acid 1 → 100)-acetonitrile (80: 20) is a mobile phase, the detection wavelength is 232nm, and theoretical cam curve is calculated by picrinine should be not less than 7000.
It is an amount of that the picrinine reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds the acetonitrile dissolving and make the solution that every 1ml contains 50 μ g.
The preparation of need testing solution is got this product and is ground, and the accurate powder 1.50g that claims puts in the 200ml conical flask, add the ammonia test solution (2% strong aqua ammonia, PH=9) 100ml extracts 2 times, filters, filtrate is used chloroform extraction 3 times, each 100ml, combining extraction liquid, water jolting washing is reclaimed solvent to doing to neutral, with acetonitrile precipitation is transferred to the 25ml volumetric flask, add acetonitrile to scale, shake up, filter, filtrate is as need testing solution.
Algoscopy is got 10 μ l reference substance solution and each 10 μ l of need testing solution respectively, injects chromatograph of liquid, and the record chromatogram is pressed external standard method with calculated by peak area, promptly.
The present composition (capsule, the tolerant 0.27g of every intragranular) contains picrinine and is not less than 20 μ g.
More than described the preferred embodiment for the present invention, so it is not in order to limit the present invention.Those skilled in the art can not depart from the improvement and the variation of category of the present invention and spirit to embodiment disclosed herein.
Claims (10)
1. Chinese medicine composition, its component by following weight proportion is formed: Radix Angelicae Sinensis volatile oil 5-90%, Folium Alstoniae Scholaris extract 95-10%, contain the indoles alkaloid that accounts for this extract gross weight 1-90% in the wherein said Folium Alstoniae Scholaris extract, contain the duck hornbeam leaf alkali that accounts for this extract gross weight 0.1-80% in this indoles alkaloid.
2. Chinese medicine composition as claimed in claim 1 contains the ligustilide that accounts for Radix Angelicae Sinensis volatile oil gross weight 30-80% in the wherein said Radix Angelicae Sinensis volatile oil.
3. the preparation method of Chinese medicine composition as claimed in claim 1 may further comprise the steps:
(1) gets the Radix Angelicae Sinensis medical material, adopt the way of distillation or supercritical fluid extraction Radix Angelicae Sinensis volatile oil;
(2) get the Folium Alstoniae Scholaris medical material, the additive polarity solvent extraction obtains the Folium Alstoniae Scholaris extract, and described polar solvent is that water or concentration are the ethanol of 10-95%, and the method for described extraction comprises decoction and/or refluxes;
(3) Radix Angelicae Sinensis volatile oil that above-mentioned (1) is obtained mixes with the extract that (2) obtain.
4. preparation method as claimed in claim 3 also comprises the volatile oil water that will obtain in the step (1) or ethanol as solvent, makes the process of volatile oil clathrate compound with the beta-schardinger dextrin-inclusion, and wherein the part by weight of volatile oil and beta-schardinger dextrin-is 1: 5-10.
5. preparation method as claimed in claim 3, wherein the polar solvent described in the step (2) is that concentration is the ethanol of 10-95%, the extracting method of described Folium Alstoniae Scholaris is with the Folium Alstoniae Scholaris alcohol reflux, concentrates, and obtains the Folium Alstoniae Scholaris extract.
6. preparation method as claimed in claim 3, wherein also comprise resulting Folium Alstoniae Scholaris extract is filtered, filtrate is handled by macroporous adsorbent resin or through cation exchange column, the step of described processing is for washing the reaction negative to molish earlier with water, the reuse ethanol elution, eluent reclaims, and concentrates drying under reduced pressure.
7. medicine for the treatment of the cough, asthma disease, comprising each described Chinese medicine composition of claim 1-3 and pharmacy acceptable auxiliary, it is a peroral dosage form.
8. the preparation method of medicine as claimed in claim 7, comprising:
(1) gets the Radix Angelicae Sinensis medical material, adopt the method for the way of distillation or supercritical extraction to prepare Radix Angelicae Sinensis volatile oil;
(2) get the Folium Alstoniae Scholaris medical material, the additive polarity solvent extraction obtains the Folium Alstoniae Scholaris extract, and described polar solvent is that water or concentration are the ethanol of 10-95%, and described extraction comprises decoction and/or refluxes;
(3) Radix Angelicae Sinensis volatile oil with above-mentioned (1) mixes with the extract that (2) obtain;
(4) add pharmacy acceptable auxiliary mixing.
9. preparation method as claimed in claim 8 comprises that also the volatile oil that will obtain in the step (1) makes the process of volatile oil clathrate compound with the beta-schardinger dextrin-inclusion, and the part by weight of volatile oil and beta-schardinger dextrin-is 1: 5-10.
10. the application of the described compositions of claim 1 in the medicine of preparation treatment cough illness.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102631396A (en) * | 2012-05-07 | 2012-08-15 | 江苏省中医药研究院 | Anti-lung cancer alstonia-leaf traditional Chinese herbal composite, method for preparing same and application thereof in preparing anti-lung cancer medicine |
| CN105010935A (en) * | 2015-06-17 | 2015-11-04 | 蚌埠市天星树脂有限责任公司 | Resin for extracting crude drug of cough relieving medicine and preparation method of the resin for extracting crude drug of cough relieving medicine |
| CN105218617A (en) * | 2015-09-30 | 2016-01-06 | 宋晓梅 | A kind of new triterpenoid and preparation method thereof and medicinal use |
| CN106226452A (en) * | 2016-08-29 | 2016-12-14 | 贵州信邦制药股份有限公司 | The discrimination method of Radix Angelicae Sinensis in SHIQUAN DABU JIU |
| CN107569538A (en) * | 2017-09-11 | 2018-01-12 | 江西傲新生物科技有限公司 | A kind of pharmaceutical preparation for preventing and treating livestock and birds respiratory disease and preparation method thereof |
| CN108697695A (en) * | 2015-11-11 | 2018-10-23 | 中国科学院昆明植物研究所 | Treat the pharmaceutical composition of respiratory disease |
| CN111867602A (en) * | 2018-03-26 | 2020-10-30 | 丽年控股有限公司 | Method for delivering amphiphilic biologically active substances targeted to the respiratory tract |
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- 2007-02-08 CN CNB2007100637240A patent/CN100563670C/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102631396A (en) * | 2012-05-07 | 2012-08-15 | 江苏省中医药研究院 | Anti-lung cancer alstonia-leaf traditional Chinese herbal composite, method for preparing same and application thereof in preparing anti-lung cancer medicine |
| CN105010935A (en) * | 2015-06-17 | 2015-11-04 | 蚌埠市天星树脂有限责任公司 | Resin for extracting crude drug of cough relieving medicine and preparation method of the resin for extracting crude drug of cough relieving medicine |
| CN105218617A (en) * | 2015-09-30 | 2016-01-06 | 宋晓梅 | A kind of new triterpenoid and preparation method thereof and medicinal use |
| CN108697695A (en) * | 2015-11-11 | 2018-10-23 | 中国科学院昆明植物研究所 | Treat the pharmaceutical composition of respiratory disease |
| CN108697695B (en) * | 2015-11-11 | 2021-08-03 | 中国科学院昆明植物研究所 | Pharmaceutical composition for treating respiratory diseases |
| CN106226452A (en) * | 2016-08-29 | 2016-12-14 | 贵州信邦制药股份有限公司 | The discrimination method of Radix Angelicae Sinensis in SHIQUAN DABU JIU |
| CN107569538A (en) * | 2017-09-11 | 2018-01-12 | 江西傲新生物科技有限公司 | A kind of pharmaceutical preparation for preventing and treating livestock and birds respiratory disease and preparation method thereof |
| CN111867602A (en) * | 2018-03-26 | 2020-10-30 | 丽年控股有限公司 | Method for delivering amphiphilic biologically active substances targeted to the respiratory tract |
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| Publication number | Publication date |
|---|---|
| CN100563670C (en) | 2009-12-02 |
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