CN105168447A - Traditional Chinese medicine composition for treating cough variant asthma - Google Patents
Traditional Chinese medicine composition for treating cough variant asthma Download PDFInfo
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- CN105168447A CN105168447A CN201510691245.8A CN201510691245A CN105168447A CN 105168447 A CN105168447 A CN 105168447A CN 201510691245 A CN201510691245 A CN 201510691245A CN 105168447 A CN105168447 A CN 105168447A
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Abstract
The invention discloses a traditional Chinese medicine composition for treating cough variant asthma and a preparation method of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from the following traditional Chinese medicine materials: tuckahoe, capillary wormwood herb, periostracum cicada, apricot seed, platycodon root, dragon's bone and licorice root. The traditional Chinese medicine composition disclosed by the invention is simple in formula, scientific and precise in compatibility, and faster and better in effect of treating the cough variant asthma, has significant effects of clearing away heat and promoting dieresis, relieving sore throat and relieving spasm, eliminating phlegm and relieving asthmatic symptom, invigorating spleen and replenishing qi, dispelling wind and clearing away lung heat and the like, and is suitable for clinical popularization and application.
Description
Technical field
The invention belongs to the field of Chinese medicines, particularly, relate to a kind of Chinese medicine composition being used for the treatment of cough variant asthma.
Background technology
Cough variant asthma (coughcariantasthma, CVA) is a kind of asthma of specific type, clinical with Chen Faxing, intractable cough for main manifestations, because its onset is hidden, the cause of disease is complicated, and delay is difficult, often cause mistaken diagnosis, fail to pinpoint a disease in diagnosis and lose control, wrong treatment.Patient is cardinal symptom with persistent cough, is mainly in night, how because cold air, flu, oil smoke suction etc. are brought out or increase the weight of, has the feature of onset concealment, course of disease delay, recurrent exerbation.What modern medicine was controlled is main mainly with inhalation Bronchodilators and inhaled etc., and Chinese medicine has compared with Western medicine, and side effect is little, persistent, the advantage not easily recurred and characteristic.Therefore, this area needs the preparation method of formula is more simple, safety better, therapeutic effect is better new medicine compositions and science more badly.
Summary of the invention
In order to achieve the above object, the present inventor provides a kind of Chinese medicine composition for the treatment of cough variant asthma; Inventor also discloses the Preparation method and use of this Chinese medicine composition on the other hand.
Specifically: inventor is found by clinical trial repeatedly, checking, Poria, Herba Artemisiae Scopariae, Periostracum Cicadae, Semen Armeniacae Amarum, Radix Platycodonis, Os Draconis and Radix Glycyrrhizae seven taste Chinese crude drug are carried out the Chinese medicine composition that compatibility obtains, acted on cough variant asthma patient, the remarkable efficacy of clearing away heat-damp and promoting diuresis, sore-throat relieving spasmolytic, eliminating phlegm and relieving asthma, invigorating the spleen and replenishing QI, loose wind lung heat clearing can be played.
To achieve these goals, the invention provides a kind of Chinese medicine composition being used for the treatment of cough variant asthma, said composition is made up of following Chinese crude drug: Poria, Herba Artemisiae Scopariae, Periostracum Cicadae, Semen Armeniacae Amarum, Radix Platycodonis, Os Draconis, Radix Glycyrrhizae.
As long as above-mentioned seven taste Chinese medicines are carried out the effect that prescription can realize treating cough variant asthma by Chinese medicine composition provided by the invention.Therefore, the purposes of this Chinese medicine composition in the medicine of preparation treatment cough variant asthma is protected in the application's request.
Although the Chinese medicine composition of above-mentioned composition can realize goal of the invention of the present invention, in order to increase coordinated between each raw material further to strengthen the effect of its treatment cough variant asthma, preferably, above-mentioned composition is made up of the Chinese crude drug of following weight proportioning: Poria 10-15 weight portion, Herba Artemisiae Scopariae 5-8 weight portion, Periostracum Cicadae 10-15 weight portion, Semen Armeniacae Amarum 10-14 weight portion, Radix Platycodonis 8-12 weight portion, Os Draconis 6-10 weight portion, Radix Glycyrrhizae 3-6 weight portion.
Further preferably, described compositions is made up of the Chinese crude drug of following weight proportioning: Poria 13 weight portion, Herba Artemisiae Scopariae 6 weight portion, Periostracum Cicadae 13 weight portion, Semen Armeniacae Amarum 12 weight portion, Radix Platycodonis 10 weight portion, Os Draconis 8 weight portion, Radix Glycyrrhizae 5 weight portion.
The function of each component of compositions of the present invention cures mainly as follows:
Poria is sweet, light, flat.GUIXIN, lung, spleen, kidney channel.Promoting diuresis to eliminate damp pathogen, spleen invigorating mind calming.For edema oliguria, phlegm retention vertigo and palpitation, insufficiency of the spleen lack of appetite, have loose bowels in loose stool, irritability, palpitation with fear insomnia.
Herba Artemisiae Scopariae, bitter, pungent, be slightly cold.Return spleen, stomach, liver, gallbladder meridian.Clearing away damp-heat, jaundice eliminating subcutaneous ulcer.For jaundice oliguria, eczema pruritus; Infectious jaundice type hepatitis.
Periostracum Cicadae, sweet, cold.Return lung, Liver Channel.Loose wind heat extraction, sore-throat relieving, rash, nebula removing, spasmolytic.For anemopyretic cold, pharyngalgia, hoarseness, measles without adequate eruption, rubella pruritus, cataract, convulsion with spasms, tetanus.
Semen Armeniacae Amarum, warm in nature, bitter in the mouth; Slightly poisonous.Return lung, large intestine channel.Sending down the abnormal ascending QI relieving cough and asthma, loosening bowel to relieve constipation.
Radix Platycodonis, bitter, pungent, flat.Return lung meridian.Lung qi dispersing, sore-throat relieving, eliminates the phlegm, evacuation of pus.For cough with copious phlegm, uncomfortable in chest not smooth, pharyngalgia, hoarseness, lung abscess vomiting pus, skin infection difficulty in discharging of pus.
Os Draconis are sweet, puckery, flat.Calmness, arresting sweating arresting seminal emission, promoting tissue regeneration and ulcer healing.For neurasthenia, cardiopalmus, insomnia, dreaminess, spontaneous perspiration, night sweat, seminal emission, the enuresis, metrorrhagia, leukorrhagia; External control skin infection for a long time burst do not hold back.
Radix Glycyrrhizae, sweet, flat.GUIXIN, lung, spleen, stomach warp.Invigorating the spleen and replenishing QI, heat-clearing and toxic substances removing, expelling phlegm for arresting cough, relieving spasm to stop pain, coordinating the actions of various ingredients in a prescription.For weakness of the spleen and stomach, fatigue and weakness, shortness of breath and palpitation, cough with copious phlegm, the anxious pain of gastral cavity abdomen, extremity contraction, carbuncle sore tumefacting virus, cushion toxicity, strong.
In Chinese medicine composition provided by the invention, all medicine compatibilities, mutually strengthen, are in harmonious proportion, and have the effects such as clearing away heat-damp and promoting diuresis, sore-throat relieving spasmolytic, eliminating phlegm and relieving asthma, invigorating the spleen and replenishing QI, loose wind lung heat clearing.Wherein, Poria, Herba Artemisiae Scopariae, promoting diuresis to eliminate damp pathogen, spleen invigorating mind calming, two medicines 5 are monarch drug with use.Periostracum Cicadae, loose wind heat extraction, sore-throat relieving spasmolytic; Radix Platycodonis, lung qi dispersing sore-throat relieving, evacuation of pus of eliminating the phlegm is ministerial drug.Semen Armeniacae Amarum, sending down the abnormal ascending QI relieving cough and asthma, loosening bowel to relieve constipation; Os Draconis, calm, arresting sweating arresting seminal emission, promoting tissue regeneration and ulcer healing is adjuvant drug.Radix Glycyrrhizae, invigorating the spleen and replenishing QI, heat-clearing and toxic substances removing, expelling phlegm for arresting cough, relieving spasm to stop pain, coordinating the actions of various ingredients in a prescription, for making medicine, directly drawing above-mentioned all medicines and going directly focus, from basic rapid healing cough variant asthma.
The Chinese medicine composition being used for the treatment of cough variant asthma provided by the invention, can make various dosage form, such as oral liquid, granule or capsule as required, and preferably, Chinese medicine composition of the present invention makes oral liquid.The preparation of above-mentioned dosage form according to the method for this area routine, such as, by above-mentioned Chinese medicine composition mixing, can be pulverized, then with pharmaceutically acceptable adjuvant Homogeneous phase mixing.
Although Chinese medicine composition of the present invention is by simple mixing, cough variant asthma can be used for the treatment of play a role, the present inventor also finds under study for action, by optimized fabrication method, serve the effect of efficacy enhancing and toxicity reducing, reduce the untoward reaction directly using medicine to produce, such that this Chinese medicine composition is more potent acts on lesion faster, further increase the compliance that patient uses this medicine.Therefore, present invention also offers a kind of method preparing the Chinese medicine composition of above-mentioned treatment cough variant asthma, the method comprises the following steps:
The Poria of recipe quantity, Semen Armeniacae Amarum, Os Draconis, Herba Artemisiae Scopariae, Radix Platycodonis, Radix Glycyrrhizae, Periostracum Cicadae are ground into coarse powder respectively, add medical material gross weight 3-6 times water gaging, decoct 2 hours, filter, taking liquid; To filter 65% ethanol water adding filter cake weight 1-2 times amount in gained filter cake, 55-65 DEG C is extracted 1 hour, filters, taking liquid; Merge twice medicinal liquid, add pharmaceutically acceptable carrier, be prepared into clinical acceptable dosage form by conventional method.
The obtained Chinese medicine composition effective active composition of said method is high, and safely, have no side effect.
Other features and advantages of the present invention are described in detail in detailed description of the invention part subsequently.
Detailed description of the invention
Below the specific embodiment of the present invention is described in detail.Should be understood that, detailed description of the invention described herein, only for instruction and explanation of the present invention, is not limited to the present invention.
Below will be described the present invention by embodiment.
Embodiment 1 capsule
The Chinese medicine composition being used for the treatment of cough variant asthma of the present invention is made up of following medical material:
Poria 10g, Herba Artemisiae Scopariae 5g, Periostracum Cicadae 10g, Semen Armeniacae Amarum 10g, Radix Platycodonis 12g, Os Draconis 10g, Radix Glycyrrhizae 6g.
The Poria of recipe quantity, Semen Armeniacae Amarum, Os Draconis, Herba Artemisiae Scopariae, Radix Platycodonis, Radix Glycyrrhizae, Periostracum Cicadae are ground into coarse powder respectively, add medical material gross weight 3-6 times water gaging, decoct 2 hours, filter, taking liquid; To filter 65% ethanol water adding filter cake weight 2 times amount in gained filter cake, 60 DEG C are extracted 1 hour, filter, taking liquid; Merge twice medicinal liquid, add pharmaceutically acceptable carrier, be prepared into capsule by conventional method.
Embodiment 2 granule
The Chinese medicine composition being used for the treatment of cough variant asthma of the present invention is made up of following medical material:
Poria 15g, Herba Artemisiae Scopariae 8g, Periostracum Cicadae 15g, Semen Armeniacae Amarum 14g, Radix Platycodonis 8g, Os Draconis 6g, Radix Glycyrrhizae 3g.
Preparation method, with embodiment 1, is prepared into granule by conventional method.
Embodiment 3 oral liquid
The Chinese medicine composition being used for the treatment of cough variant asthma of the present invention is made up of following medical material:
Poria 13g, Herba Artemisiae Scopariae 6g, Periostracum Cicadae 13g, Semen Armeniacae Amarum 12g, Radix Platycodonis 10g, Os Draconis 8g, Radix Glycyrrhizae 5g.
Preparation method, with embodiment 1, is prepared into oral liquid by conventional method.
Embodiment 4 oral liquid
The Chinese medicine composition being used for the treatment of cough variant asthma of the present invention is made up of following medical material:
Poria 20g, Herba Artemisiae Scopariae 10g, Periostracum Cicadae 8g, Semen Armeniacae Amarum 16g, Os Draconis 15g, Radix Glycyrrhizae 2g.
Preparation method, with embodiment 1, is prepared into oral liquid by conventional method.
Embodiment 5 oral liquid
The Chinese medicine composition being used for the treatment of cough variant asthma of the present invention is made up of following medical material:
Poria 13g, Radix Scutellariae 10g, Herba Artemisiae Scopariae 6g, Fructus Forsythiae 10g, Semen Armeniacae Amarum 12g, Radix Platycodonis 10g, Os Draconis 8g, Radix Glycyrrhizae 5g.
Preparation method, with embodiment 1, is prepared into oral liquid by conventional method.
Test example 1 Chinese medicine composition oral liquid of the present invention is used for clinical observation test
1. physical data:
This test example chooses 160 routine cough variant asthma patients, is divided into test I, II, III, IV group at random.Wherein test I group of man 16 example, female 24 example; Age 32-56 year, year mean age (38.2 ± 1.41); Individual month of average course of disease (4.2 ± 0.65).Test II group of man 15 example, female 25 example; Age 31-60 year, year mean age (37.5 ± 1.35); Individual month of average course of disease (4.1 ± 0.60).Test III group of man 16 example, female 24 example; Age 31-55 year, year mean age (38.0 ± 1.40); Individual month of average course of disease (4.0 ± 0.60).Test IV group of man 17 example, female 23 example; Age 33-56 year, year mean age (38.5 ± 1.43); Individual month of average course of disease (4.3 ± 0.66).Four groups of sexes, age, courses of disease etc. compare, and difference there are no significant meaning (P > 0.05), has comparability.
2. case selection standard
Doctor trained in Western medicine is made a definite diagnosis with reference to " the Clinics and Practices guide of cough "; Patient's maximal expiratory flow day-night change rate is more than 20%; Application bronchodilator successful.
About the diagnostic criteria of cough variant asthma is made a definite diagnosis in traditional Chinese medical science reference " cough Chinese traditional medical diagnose Consensus of experts suggestion (2011 editions) ".The visible syndrome of patient: the few expectorant of dry cough or without expectorant, dry pharynx dryness in the nasal cavity, coughs very chest pain, or expectorant is glutinous not easily brings up, from the beginning of having aversion to cold, fever of the body is had a headache, red tip of the tongue, yellow and thin fur, small pulse and count, and Chinese medical discrimination is that pathogenic dryness impairing the lung is demonstrate,proved.
3. exclusion standard
1) patient that treatments period compliance is poor, take the treatment of its medicine or drop by the wayside is got rid of;
2) patient suffering from the diseases such as pneumonia, tuberculosis, tumor is got rid of;
3) patient that there are the organic diseases such as congenital Liver and kidney is got rid of;
4) get rid of and there is mental disorder, mental maladjustment, can not the patient of partner treatment;
5) patient medication being existed to severe allergic reaction is got rid of;
6) trimester of pregnancy, breast-feeding female is got rid of;
7) Chronic Cough Patients that other reasons causes is got rid of.
4. process of the test:
Test I group: take oral liquid prepared by embodiment 3, every bottle contains crude drug amount 5g, each 1 bottle, every day 2 times.
Test II group: take oral liquid prepared by embodiment 4, every bottle contains crude drug amount 5g, each 1 bottle, every day 2 times.
Test III group: take oral liquid prepared by embodiment 5, every bottle contains crude drug amount 5g, each 1 bottle, every day 2 times.
Test IV group: give albuterol aerosol (the accurate word H50020453 of traditional Chinese medicines) treatment, suck 100 ~ 200 μ g at every turn, i.e. 1 ~ 2 spray, can suck once every 4 ~ 8h if desired, but at most no more than 8 sprays in 24h.
Within one week, be a course for the treatment of, after two courses for the treatment of, add up therapeutic effect.
5. result of the test:
Therapeutic evaluation is carried out with reference to " Chinese medical disease Standardization of diagnosis and curative effect ":
1. fully recover: patients symptomatic all disappears;
2. effective: patients symptomatic obviously alleviates, cough frequency is reduced by least 2/3; Transference cure in 1 week after treatment.
3. effective: patient clinical symptom takes a turn for the better, and cough frequency is reduced by least 1/3; After treatment, in 1 week, symptom alleviates;
4. invalid: patient clinical symptom has no significant change.
Total effective rate=(recovery from illness number of cases+effective number of cases+effectively number of cases)/total patient's number × 100%.
5. statistical method
Carry out statistical analysis with statistics software SPSS20.0 to data, enumeration data adopts x
2inspection; Measurement data mean ± standard deviation (
) represent, carry out t inspection; P < 0.05 represents that between two groups, diversity is remarkable.
6. therapeutic outcome
1) the concrete therapeutic outcome testing each group is as shown in table 1.
Table 1: two groups for the treatment of clinical effectiveness
| Group | Recovery from illness | Effective | Effectively | Invalid | Effective percentage |
| Test I group (40 people) | 28 | 8 | 3 | 1 | 97.5％* ◎&& |
| Test II group (40 people) | 17 | 6 | 5 | 12 | 70.0％ |
| Test III group (40 people) | 16 | 5 | 6 | 13 | 67.5％ |
| Test IV group (40 people) | 13 | 5 | 7 | 15 | 62.5％ |
Note: test I group and compare with test II group,
*p < 0.05,
*p < 0.01; Compare with test II group,
◎p < 0.05,
◎ ◎p < 0.01; Compare with test II group,
aMP.AMp.Ampp < 0.05,
aMP.AMp.Amp &p < 0.01.
As can be seen from table 1 relatively, test in I group 28 people that fully recover, total effective rate 97.5%, be all better than other test group, and significant difference or very remarkable, there is statistical significance (P < 0.05, P < 0.01).
Meanwhile, using the test I group of Chinese medicine composition oral liquid of the present invention not find untoward reaction, observing half a year to test I group recovery from illness patient Continuous Tracking subsequently, not finding the phenomenon that case recurs.This Chinese medicine preparation, under instruction of Chinese Medicine theory, adopts high-quality, authentic medicinal herbs, processes, steady quality through specification procedure, there is composition unification, taking convenience, be beneficial to carry, the feature of determined curative effect, be worthy to be popularized.
2) change of two groups of Pulmonary Function indexs is compared two groups of Pulmonary Functions and is improved after treatment obviously, with pulmonary function closely-related 1st second forced expiratory volume (FEV
1), test I group of improvement more outstanding, diversity is significantly (P<0.05).In table 2.
Table 2 patient cough variant FEV
1relatively (
l)
| Group | Before treatment | After treatment |
| Test I group (40 people) | 1.58±0.18 | 3.68±0.31 ##※※◆◆11 |
| Test II group (40 people) | 1.49±0.15 | 2.40±0.28 2 |
| Test III group (40 people) | 1.55±0.16 | 2.52±0.26 3 |
| Test IV group (40 people) | 1.52±0.10 | 2.77±0.26 4 |
Note: after treatment, test I group is compared with test II group,
#p < 0.05,
##p < 0.01; Compare with test II group,
※p < 0.05,
※ ※p < 0.05; Compare with test II group,
◆p < 0.05,
◆ ◆p < 0.05;
Compare with after treatment before testing I group for the treatment of,
1p < 0.05,
11p < 0.01; Compare with after treatment before testing II group for the treatment of,
2p < 0.05,
22p < 0.01; Compare with after treatment before testing III group for the treatment of,
3p < 0.05,
33p < 0.01; Compare with after treatment before testing IV group for the treatment of,
4p < 0.05,
44p < 0.01.
As can be seen from Table 2, in healing patient, test I group with after treatment and test II-IV group treat after compared with there is difference (P < 0.01) very significantly, with before treatment, also all there were significant differences (P < 0.05) after the treatment of test II-IV group, but the result there was no significant difference (P > 0.05) after test II-IV treatment, also namely use Chinese medicine composition oral liquid provided by the invention can cure patient faster, and test II-IV group without test effect of the present invention.
To sum up, the invention provides a kind of Chinese medicine composition and preparation method thereof, this Traditional Chinese medicine composition formula is simple, compatibility scientific and precise, treatment cough variant asthma effect are faster, better, has the remarkable efficacy of clearing away heat-damp and promoting diuresis, sore-throat relieving spasmolytic, eliminating phlegm and relieving asthma, invigorating the spleen and replenishing QI, loose wind lung heat clearing.In addition, the method preparing Chinese medicine composition provided by the invention, utilize the effective ingredient of modern preparation technology's rapid extraction said composition, the method is simple, is applicable to promoting production in enormous quantities.
More than describe the preferred embodiment of the present invention in detail; but the present invention is not limited to the detail in above-mentioned embodiment, within the scope of technical conceive of the present invention; can carry out multiple simple variant to technical scheme of the present invention, these simple variant all belong to protection scope of the present invention.
It should be noted that in addition, each concrete technical characteristic described in above-mentioned detailed description of the invention, in reconcilable situation, can be combined by any suitable mode, in order to avoid unnecessary repetition, the present invention illustrates no longer separately to various possible compound mode.
In addition, also can carry out combination in any between various different embodiment of the present invention, as long as it is without prejudice to thought of the present invention, it should be considered as content disclosed in this invention equally.
Claims (7)
1. one kind is used for the treatment of the Chinese medicine composition of cough variant asthma, it is characterized in that, described compositions is made up of the Chinese crude drug of following weight proportioning: Poria 10-15 weight portion, Herba Artemisiae Scopariae 5-8 weight portion, Periostracum Cicadae 10-15 weight portion, Semen Armeniacae Amarum 10-14 weight portion, Radix Platycodonis 8-12 weight portion, Os Draconis 6-10 weight portion, Radix Glycyrrhizae 3-6 weight portion.
2. the Chinese medicine composition being used for the treatment of cough variant asthma according to claim 1, it is characterized in that, described compositions is made up of the Chinese crude drug of following weight proportioning: Poria 13 weight portion, Herba Artemisiae Scopariae 6 weight portion, Periostracum Cicadae 13 weight portion, Semen Armeniacae Amarum 12 weight portion, Radix Platycodonis 10 weight portion, Os Draconis 8 weight portion, Radix Glycyrrhizae 5 weight portion.
3. the Chinese medicine composition being used for the treatment of cough variant asthma according to claim 1 and 2, is characterized in that, the dosage form of this Chinese medicine composition is oral liquid, granule, capsule.
4. the Chinese medicine composition being used for the treatment of cough variant asthma according to claim 3, is characterized in that, the dosage form of this Chinese medicine composition is preferably oral liquid.
5. prepare the method being used for the treatment of the Chinese medicine composition of cough variant asthma described in claim 1 or 2, it is characterized in that, the method comprises the following steps:
The Poria of recipe quantity, Semen Armeniacae Amarum, Os Draconis, Herba Artemisiae Scopariae, Radix Platycodonis, Radix Glycyrrhizae, Periostracum Cicadae are ground into coarse powder respectively, add medical material gross weight 3-6 times water gaging, decoct 2 hours, filter, taking liquid; To filter 65% ethanol water adding filter cake weight 1-2 times amount in gained filter cake, 55-65 DEG C is extracted 1 hour, filters, taking liquid; Merge twice medicinal liquid, add pharmaceutically acceptable carrier, be prepared into clinical acceptable dosage form by conventional method.
6. the purposes of Chinese medicine composition as claimed in claim 1 or 2 in the medicine of preparation treatment cough variant asthma.
7. the purposes of Chinese medicine composition as claimed in claim 1 or 2 in the medicine of preparation treatment pathogenic dryness impairing the lung type cough variant asthma.
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| CN105596453A (en) * | 2016-01-11 | 2016-05-25 | 济南康众医药科技开发有限公司 | Pharmaceutical composition for treating cough variant asthma and pharmacologic action thereof |
| CN106109890A (en) * | 2016-08-11 | 2016-11-16 | 佘晖 | A kind of Chinese medicine composition treating cough variant asthma |
| CN106237244A (en) * | 2016-08-30 | 2016-12-21 | 山东省文登整骨医院 | A kind of Chinese medicinal formulae treating asthma |
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| CN104971274A (en) * | 2014-04-08 | 2015-10-14 | 刘黎明 | Traditional Chinese medicine composition for treating cough variant asthma |
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| CN104971274A (en) * | 2014-04-08 | 2015-10-14 | 刘黎明 | Traditional Chinese medicine composition for treating cough variant asthma |
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| CN105596453A (en) * | 2016-01-11 | 2016-05-25 | 济南康众医药科技开发有限公司 | Pharmaceutical composition for treating cough variant asthma and pharmacologic action thereof |
| CN106109890A (en) * | 2016-08-11 | 2016-11-16 | 佘晖 | A kind of Chinese medicine composition treating cough variant asthma |
| CN106237244A (en) * | 2016-08-30 | 2016-12-21 | 山东省文登整骨医院 | A kind of Chinese medicinal formulae treating asthma |
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Application publication date: 20151223 |