CN1861153A - Medicinal composition used for treating pharyngitis, its prepn. method and its quality control method - Google Patents

Medicinal composition used for treating pharyngitis, its prepn. method and its quality control method Download PDF

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CN1861153A
CN1861153A CN 200610042650 CN200610042650A CN1861153A CN 1861153 A CN1861153 A CN 1861153A CN 200610042650 CN200610042650 CN 200610042650 CN 200610042650 A CN200610042650 A CN 200610042650A CN 1861153 A CN1861153 A CN 1861153A
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water
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radix
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volatile oil
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CN100376274C (en
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庞来祥
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Shandong Danhong Pharmaceutical Co Ltd
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Abstract

A Chinese medicine for treating pharyngitis, laryngitis, laryngalgia, tonsillitis, etc is prepared from 16 Chinese-medicinal materials including honeysuckle flower, mint, arctium fruit, platycodon root, etc. Its quality control method includes the thin-layer discrimination to mint, arctium fruit, liquorice root, platycodon root and ophiopogon root, examining the relative density and pH value and measuring the contents of honeysuckle flower and chrysanthemum. Its preparing process is also disclosed.

Description

The pharmaceutical composition and method for making and the method for quality control that are used for the treatment of sore throat
Technical field
The present invention relates to a kind of pharmaceutical composition and method for making thereof and method of quality control, especially for pharmaceutical composition and the method for making and the method for quality control of treatment sore throat.
Background technology
Acute and chronic pharyngitis is common clinical, frequently-occurring disease, belongs to traditional Chinese medical science sore throat category, and the Chinese herb decoction opinion is controlled, and reasonable curative effect is arranged.Chinese patent gazette disclosed name to be called " peaceful aerosol of quick-acting throats and compound method ", publication number was 1117862 patent application on March 6th, 1996, this aerosol medicinal liquid is mainly made by Radix Scrophulariae, Flos Lonicerae, Fructus Forsythiae, Rhizoma Belamcandae, Radix Sophorae Tonkinensis, Radix Platycodonis, Oleum menthae, Borneolum Syntheticum, Borax etc., lays particular emphasis on heat-clearing and toxic substances removing.And contain Radix Ophiopogonis, Radix Glehniae, Fructus Corni (processed), Fructus Crataegi, Radix Glycyrrhizae in the present invention's prescription, and lay particular emphasis on nourishing lung and kidney, sour sweet stomach function regulating, be intended to effect a permanent cure.2005 editions " Chinese pharmacopoeia liyan jiedu granule is by making Radix Isatidis, Flos Lonicerae, Fructus Forsythiae, Herba Menthae, Fructus Arctii (parched), Fructus Crataegi (parched to brown), Radix Platycodonis, Folium Isatidis, Bombyx Batryticatus, Radix Scrophulariae, Radix Scutellariae, Radix Rehmanniae, Radix Trichosanthis, Radix Et Rhizoma Rhei, Bulbus Fritillariae Thunbergii, Radix Ophiopogonis.By comparison, the present invention attached flavour of a drug Fructus Corni, Radix Glehniae, Radix Ophiopogonis with nourishing lung and kidney, Yin-nourishing and body fluid promoting, is intended to fundamentally deal with problems on the basis of heat-clearing and toxic substances removing; And the prescription in the pharmacopeia is formed with relieving the exterior syndrome with drugs of pungent in flavor and cool in nature, and removing heat from the lung and relieving sorethroat, to bring down a fever be main, except that Fructus Arctii, Herba Menthae, used flavour of a drug such as Radix Scutellariae, Radix Trichosanthis, Radix Et Rhizoma Rhei.
Summary of the invention
The objective of the invention is to: provide a kind of treatment evident in efficacy acute and chronic bronchitis, the pharmaceutical composition of upper respiratory tract infection and method for making thereof and method of quality control.
The present invention is achieved in that according to components by weight percent and calculates, and makes this pharmaceutical composition raw materials of effective components to be: Flos Lonicerae 50-150g, Fructus Forsythiae 50-150g, Fructus Arctii 25-75g, Herba Houttuyniae 25-75g, Herba Menthae 18-53g, Flos Chrysanthemi 18-53g, Rhizoma Belamcandae 50-150g, Radix Sophorae Tonkinensis 25-75g, Radix Scrophulariae 50-150g, Radix Platycodonis 18-53g, Semen Sterculiae Lychnophorae 18-53g, Radix Ophiopogonis 50-150g, Radix Glehniae 18-53g, Fructus Corni (processed) 50-150g, Fructus Crataegi 50-150g, Radix Glycyrrhizae 10-30g.Best: Flos Lonicerae 100g, Fructus Forsythiae 100g, Fructus Arctii 50g, Herba Houttuyniae 50g, Herba Menthae 35g, Flos Chrysanthemi 35g, Rhizoma Belamcandae 100g, Radix Sophorae Tonkinensis 50g, Radix Scrophulariae 100g, Radix Platycodonis 35g, Semen Sterculiae Lychnophorae 35g, Radix Ophiopogonis 100g, Radix Glehniae 35g, Fructus Corni (processed) 100g, Fructus Crataegi 100g, Radix Glycyrrhizae 20g.
Pharmaceutical composition of the present invention can be made acceptable forms on the pharmaceutics, comprise pill, granule, tablet, syrup, mixture, oral liquid, drop pill, capsule, injection, slow releasing preparation or controlled release preparation etc., preferred oral liquid, syrup, granule, capsule, tablet, special preferred oral liquid.
Medicament composition granule agent preparation method of the present invention: Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add the water distillation, and it is standby to extract volatile oil, and debris device is in addition collected, and volatile oil is made clathrate; All the other Flos Loniceraes, Fructus Arctii etc. 13 flavor decocts with water, and filters, and will extract the medicinal residues adding behind the volatile oil again, decoct with water, filter merging filtrate and above-mentioned debris, concentrating under reduced pressure, get supernatant and reclaim ethanol and be condensed into extractum, add appropriate amount of auxiliary materials, granulate, dry, with volatile oil clathrate compound mixing, packing, promptly.
Medicament composition capsule agent preparation method of the present invention: Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add the water distillation, and it is standby to extract volatile oil, and debris device is in addition collected, and volatile oil is made clathrate; All the other Flos Loniceraes, Fructus Arctii etc. 13 flavor decocts with water, and filters, and will extract the medicinal residues adding behind the volatile oil again, decoct with water, filter merging filtrate and above-mentioned debris, concentrating under reduced pressure, get supernatant and reclaim ethanol and be condensed into extractum, add appropriate amount of auxiliary materials, granulate, dry, with the volatile oil clathrate compound mixing, encapsulated, promptly.
Pharmaceutical composition method for preparing tablet thereof of the present invention: Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add the water distillation, and it is standby to extract volatile oil, and debris device is in addition collected, and volatile oil is made clathrate; All the other Flos Loniceraes, Fructus Arctii etc. 13 flavor decocts with water, and filters, and will extract the medicinal residues adding behind the volatile oil again, decoct with water, filter merging filtrate and above-mentioned debris, concentrating under reduced pressure is got supernatant and is reclaimed ethanol and be condensed into extractum, adds appropriate amount of auxiliary materials, granulate, drying is with volatile oil clathrate compound mixing, tabletting, packing, promptly.
Pharmaceutical composition syrup preparation method of the present invention: Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add the water distillation, and it is standby to extract volatile oil, and debris device is in addition collected; All the other Flos Loniceraes, Fructus Arctii etc. 13 flavor decocts with water, and filters, and the medicinal residues that will extract again behind the volatile oil add, and decoct with water, filter, and merging filtrate and above-mentioned debris, concentrating under reduced pressure is got supernatant and is reclaimed ethanol and concentrated; Other gets sucrose and makes syrup, with above-mentioned concentrated solution mixing, boils, and puts coldly, and appropriate amount of auxiliary materials transfers to 1000ml, packing, and sterilization, promptly.
Drug composition oral liquid and preparation method thereof of the present invention: Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add the water distillation, and it is standby to extract volatile oil, and debris device is in addition collected; All the other Flos Loniceraes, Fructus Arctii etc. 13 flavor decocts with water, and filters, and will extract the medicinal residues adding behind the volatile oil again, decoct with water, filter merging filtrate and above-mentioned debris, concentrating under reduced pressure is got supernatant and is reclaimed ethanol and concentrated, gets supernatant and filters, filtrate adds above-mentioned volatile oil and appropriate amount of auxiliary materials, transfer to 1000ml, filter packing, sterilization, promptly.Preferably: Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add 14 times of water gaging distillations 6 hours, and it is standby to extract volatile oil, and debris device is in addition collected; All the other Flos Loniceraes, 13 flavors such as Fructus Arctii decoct with water three times, and 2 hours for the first time, 1.5 hours for the second time, amount of water is respectively 12 times and 10 times, and collecting decoction filters, medicinal residues behind medicinal residues and the extraction volatile oil merge, and add 10 times of water gagings again, decoct 1 hour, filter, merging filtrate and above-mentioned debris, relative density is 1.10~1.12 when being evaporated to 60 ℃, adding ethanol makes and contains alcohol amount and reach 70%, left standstill 24 hours, relative density is 1.04 when getting supernatant recovery ethanol and being concentrated into 20 ℃, leaves standstill 48 hours, getting supernatant filters, filtrate adds volatile oil and appropriate amount of auxiliary materials, adjusts volume to 1000ml, adjust pH to 5.0~7.0, filter, packing, sterilization, promptly.
The method of quality control of drug composition oral liquid of the present invention is as follows:
[character] this product is the sepia supernatant liquid; Gas is refrigerant, the sweet little hardship of distinguishing the flavor of.
This product 20ml is got in [discriminating] (1), and with petroleum ether (60 ~ 90 ℃) 15ml extraction 1 time, extract is concentrated into about 1ml, as need testing solution.It is an amount of that other gets the Mentholum reference substance, makes the solution that every 1ml contains 2mg with ether, in contrast product solution.Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned two kinds of each 2ul of solution, putting respectively on same silica gel G plate, is developing solvent with benzene-ethyl acetate (19: 1), launches, take out, dry, spray is with vanillin sulphuric acid-ethanol (2: 8) test solution, and 100 ℃ of heating 5min are to clear spot, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on show identical aubergine speckle.
(2) get this product 15ml, add ammonia 1.5ml jolting mixing, use chloroform extraction three times, each 25ml, combined chloroform liquid, water bath method, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Fructus Arctii control medicinal material 1g, adds ethanol 20ml, and reflux 1h filters, and filtrate evaporate to dryness, residue add ethanol 2ml makes dissolving, in contrast medical material solution.According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same above-mentioned silica gel g thin-layer plate, with chloroform-methanol (10: 1) is developing solvent, launches, and takes out, dry, spray is with 10% sulphuric acid ethanol test solution, and 105 ℃ to be heated to speckle colour developing clear.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical blue spot.
(3) get this product 20ml, put in the separatory funnel, use water saturation n-butanol extraction 3 times, each 15ml merges n-butyl alcohol liquid, washes with water 3 times, each 20ml, and water bath method, residue add methanol 2ml makes dissolving, as need testing solution.Extracting liquorice control medicinal material 1g in addition, the 40ml that adds diethyl ether, reflux 1h, filter, medicinal residues add methanol 30ml reflux 1h, filter, filtrate evaporate to dryness, residue add water 40ml makes dissolving, uses n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, washes with water 3 times, each 20ml, n-butyl alcohol liquid evaporate to dryness, residue add methanol 5ml makes dissolving, in contrast medical material solution.Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned two kinds of each 2ul of solution, put respectively on same silica gel G plate, (15: 1: 1.5: 2) be developing solvent, expansion was taken out with ethyl acetate-formic acid-glacial acetic acid-water, dry, spray is with 10% sulphuric acid ethanol test solution, and 105 ℃ to be heated to the speckle colour developing clear, puts under the uviol lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the speckle of same color.
(4) get this product 10ml, put in the round-bottomed flask, add hydrochloric acid 3ml, water-bath reflux 30 minutes, cool, put in the separatory funnel, extract 3 times the combined ethyl acetate extracting solution with the ethyl acetate jolting, water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Platycodonis control medicinal material powder 1g, adds 7% sulphuric acid alcohol-water (1: 3) mixed liquor 20ml, reflux 3 hours, put coldly, extract 2 times each 20ml with the chloroform jolting, combined chloroform liquid, add water 30ml washing, discard washing liquid, the chloroform solution anhydrous sodium sulfate dehydration, filter, filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution.According to Chinese Pharmacopoeia thin layer chromatography test, draw need testing solution 10ul, reference substance solution 5ul, put respectively in same be on the silica gel G plate of adhesive with the sodium carboxymethyl cellulose, be developing solvent with chloroform-ether (1: 1), launch, taking-up is dried.Spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ to be heated to the speckle colour developing clear.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(5) get this product 20ml, put in the round-bottomed flask, add hydrochloric acid 6ml, water-bath reflux 1 hour cools, and puts in the separatory funnel, extracts 3 times with the ethyl acetate jolting, and combined ethyl acetate extracting solution, water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Other gets control medicinal material 1g Radix Ophiopogonis, adds water 10ml, decocts 30 minutes, filter, filtrate adds hydrochloric acid 2ml, and heating makes and keeps little boiling 10 minutes, cools, put in the separatory funnel, extract 3 times combined ethyl acetate extracting solution, water bath method with the ethyl acetate jolting, residue adds methanol 1ml makes dissolving, in contrast medical material solution; According to Chinese Pharmacopoeia thin layer chromatography test, draw need testing solution 10ul, reference substance solution 5ul, put respectively in same be on the silica gel G plate of adhesive with the sodium carboxymethyl cellulose, be developing solvent with chloroform-acetone (4: 1), launch, taking-up is dried.Spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ to be heated to the speckle colour developing clear.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
[inspection] relative density: should be not less than 1.03.
PH value: should be 5.0~7.0.
Other: should meet " the pertinent regulations under the Chinese pharmacopoeia mixture item.
[assay] is according to the Chinese Pharmacopoeia high effective liquid chromatography for measuring.
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; The glacial acetic acid solution of methanol-0.5% (20: 80) is a mobile phase; The detection wavelength is 327nm; Theoretical cam curve is pressed the chlorogenic acid peak and is calculated, and should be not less than 2000.
The preparation of reference substance solution: it is an amount of that precision takes by weighing the chlorogenic acid reference substance, adds methanol and make the solution that every ml contains 25ug, in contrast product solution.
The preparation of need testing solution: accurate this product 1ml that draws, put in the volumetric flask of 25ml, add 50% methanol and be diluted to scale, shake up, as need testing solution.
Algoscopy: accurate respectively reference substance solution and each 5ul of need testing solution of drawing, inject chromatograph of liquid, measure, promptly.
The every 10ml of this product contains Flos Lonicerae and Flos Chrysanthemi with chlorogenic acid (C 16H 18O 9) meter, should be not less than 3.0mg.
The traditional Chinese medical science thinks that the sore throat endogenous cause of ill mostly is the visceral dysfunction of lung, spleen, stomach, and exopathogenic factor mostly is wind heat and invades (or wind and cold strongly fragrant and heat-transformation), and pyretic toxicity follows through last heap soil or fertilizer over and around the roots, so that QI and blood is retarded by silt, venation numbness resistance and falling ill.This composition prescription is a monarch drug with Flos Lonicerae, Fructus Forsythiae, the heat clearing away of Radix Scrophulariae medicine, detoxifcation, eliminating stagnation; With Radix Ophiopogonis, Radix Glehniae, Fructus Corni nourishing lung and kidney is ministerial drug; Fructus Arctii, Flos Chrysanthemi, Radix Sophorae Tonkinensis, Rhizoma Belamcandae, Semen Sterculiae Lychnophorae resolving toxin and disinhibiting the throat eliminating stagnation, Herba Menthae, Radix Platycodonis lung qi dispersing are antipruritic, the Herba Houttuyniae heat-clearing and toxic substances removing, more than be adjuvant drug altogether; Fructus Crataegi, the sweet stomach function regulating coordinating the actions of various ingredients in a prescription of glycyrrhizic acid are messenger drug.All medicines gather heat-clearing and toxic substances removing, enriching yin and nourishing kidney, eliminating stagnation effect altogether, are used for the treatment of the diseases such as laryngopharynx swelling and pain that acute and chronic pharyngitis, neurosis of pharynx, tonsillitis and flu cause.
We have carried out following pharmacodynamics test with drug composition oral liquid of the present invention.
(1) analgesic experiment: adopt hot plate method and glacial acetic acid writhing method to test respectively.Get 70 of female (hot plate method) or male and female half and half (writhing method) mices, be divided into 7 groups at random, 10 every group.Be respectively: blank group (normal saline), positive controls, the present invention (1.045g/kg), the present invention (3.135g/kg), the present invention (5.225g/kg), the present invention (8.36g/kg), the present invention (10.45g/kg).Concrete test data is listed in table 1, table 2, table 3 and the table 4.
Table 1 the present invention is to mice analgesic activity hot plate reaction result (threshold of pain unit: second)
Group N (only) Dosage (g/kg) The preceding threshold of pain of administration (second) The threshold of pain (second)
15 minutes 30 minutes 60 minutes 90 minutes
The present invention of normal saline group morphine hydrochloride group 10 10 10 10 10 10 10 - 0.0075 1.045 3.135 5.225 8.36 10.45 21.3±4.42 20.4±6.27* 18.5±4.06 21.25±3.28 23.2±4.61 19.8±3.45 22.7±5.39 24.6±4.16 46.0±14.8* 25.0±8.69 31.25±9.75 30.4±9.27 29.0±13.61 27.8±7.94 24.5±2.99 43.7±15.6* 27.6±15.2 34.4±11.33* 32.4±9.82* 29.0±13.47 29.9±6.70* 25.2±4.96 38.3±10.9* 33.1±16.7 32.38±16.9 29.6±14.92 26.2±9.73 31.6±7.66* 25.1±6.15 23.4±13.1* 33.6±13.85 27.0±9.82 29.6±14.61 19.5±2.17 35.7±12.38
With normal saline group contrast * p<0.05
Table 2 the present invention is to the percentile influence of easing pain of the mice hot plate threshold of pain
Group 15 minutes 30 minutes 60 minutes 90 minutes
Physiological saline Zu morphine hydrochloride Zu 1.045g/kg of the present invention 3.135g/kg of the present invention 5.225g.kg of the present invention 8.36g/kg of the present invention 10.45g/kg of the present invention 15.5% 125.0% 35.0% 47.1% 31.0% 25.3% 22.5% 15.0% 114.0% 49.2% 61.8% 39.7% 46.5% 31.7% 18.3% 87.7% 78.9% 52.4% 19.8% 46.5% 39.2% 17.8% 14.7% 81.6% 27.1% 27.6% 32.3% 57.3%
1 mouse writhing number of times of table 3 administration and pain incidence rate
Group Number of animals (only) Dosage (g/kg) Turn round the body number of times The pain incidence rate
The present invention of the present invention of physiological saline Zu enteric coated aspirin 10 10 10 10 10 10 10 - 0.005 1.045 3.135 5.225 8.36 10.45 31.1±19.4 11.1±13.58* 28.1±16.67 27.0±10.26 22.5±11.32 27.5±20.30 22.3±18.62* 100% 80% 100% 100% 100% 80% 90%
With normal saline group contrast * p<0.05
3 (3 days) mouse writhing number of times of table 4 successive administration and pain incidence rate
Group Number of animals (only) Dosage (g/kg) Turn round the body number of times The pain incidence rate
The present invention of the present invention of physiological saline Zu enteric coated aspirin 10 10 10 10 10 10 10 - 0.005 1.045 3.135 5.225 8.36 10.45 25.9±18.85 0.8±1.39** 11.3±13.70** 11.7±13.24** 14.2±17.5** 14.75±13.60** 3.3±5.35** 100% 70% 90% 80% 80% 100% 70%
With normal saline group contrast * * p<0.01
(2) antiinflammatory experiment: carried out experiments such as influence, the scorching experiment of influence, Mice Auricle caused by dimethylbenzene xylene, the swollen experiment of rat granuloma, the experiment of rabbit Oleum Terebinthinae pharyngitis respectively to the immunosuppressed mice immune organ weight to normal mouse immune organ.Concrete test data sees for details in table 5, table 6, table 7, table 8, the table 9.
Table 5 the present invention is to normal mouse immune organ weight's influence
Group Animal (only) Give about dosage (g/kg) Breast arteries and veins (mg) Spleen (g) Liver (g)
The present invention of the present invention of normal saline group 10 10 10 10 10 10 - 1.045 3.135 5.225 8.36 10.46 104.19±31.87 93.67±23.71 89.58±28.34 106.81±31.79 92.62±18.54 82.62±17.05 0.16±0.07 0.14±0.04 0.14±0.03 0.17±0.04 0.13±0.03 0.12±0.04 1.77±0.36 1.49±0.22 1.48±0.29 1.44±0.13* 1.49±0.35 1.31±0.20
Normal saline group contrast * p<0.05
Table 6 the present invention is to the influence of immunosuppressed mice immune organ weight
Group Number of animals (only) Give about dosage (g/kg) Thymus (mg) Spleen (g) Liver (g)
The present invention of the present invention of physiological saline cyaniding cortisone 10 10 10 10 10 10 10 - 0.01ml/g 1.045 3.135 5.225 8.36 10.45 908.9±239.0 329.3±152.18** 373.3±154.4** 383.2±126.7** 379.4±205.3 343.3±174.5** 274.2±104.5** 0.12±0.003 0.07±0.029** 0.12±0.030 0.11±0.030 0.09±0.020 0.08±0.026** 0.10±0.020** 1.12±0.26 0.83±0.18** 1.13±0.28 1.04±0.19 1.00±0.18 0.83±0.17** 0.95±0.21
With normal saline group contrast * * p<0.01
Table 7 the present invention is to the bullate influence of mice dimethylbenzene ear
Group n Dosage (g/kg) Swelling degree (mg)
Dosage group small dose group of the present invention among the present invention of the heavy dose of group of the positive group of matched group (model group) the present invention 10 10 10 10 10 - 0.1 5.225 3.135 1.045 4.71±1.81 2.16±1.81 1.18±1.10 0.81±0.36 2.13±1.41
Table 8 the present invention is to the bullate influence of rat granuloma
Group n Dosage (g/kg) Granuloma weight (mg)
A left side Right
Dosage group small dose group in the heavy dose of group of the positive group of matched group 9 8 8 9 10 - 0.05 5.225 3.315 1.045 65.51±3.71 56.52±2.06* 57.93±0.09* 59.09±3.21* 59.45±4.42 67.26±3.32 56.90±6.62* 59.39±4.25* 60.33±6.66* 64.97±8.06
Annotate: compare * p<0.05 with matched group.
Table 9 the present invention tests rabbit Oleum Terebinthinae pharyngitis
Group Dosage (g/kg) N The result observes
Blank group model group treatment group 3.315 888 The pharyngeal chronic congestion state that is of the pharyngeal normal rabbits of rabbit, kermesinus, glossiness is not good enough, the mucus secretions increase, mucous epithelium is the prominent shape hypertrophy of nail, lamina propria is swelling in various degree, blood vessel hyperplasia.Treatment group state promptly is tending towards normal near the blank group
(3) extracorporeal bacteria inhibitor test: adopt the quantitative dilution method of meat soup (percentage concentration) to measure; Stock solution of the present invention (2.0g/ml).Concrete test data is listed in the table 10.
Table 10 the present invention is to minimal bactericidal concentration (MBC, %) mensuration of common respiratory tract pathogenic bacterium
Medicine Staphylococcus aureus Escherichia coli Bacillus pyocyaneus Group B streptococcus Streptococcus pneumoniae
The present invention 10.0 10.0 60.0 10.0 10.0
Above experimental result shows that the present composition can reduce the acetic acid twisting number of times of mice; Reduce the swollen weight of rat granuloma, alleviate pedal swelling degree and mice auricle swelling degree due to the rat Ovum Gallus domesticus album.But not only early stage the oozing out, swelling and ache of occurring of inflammation-inhibiting of the present composition is described, the granulation tissue hyperplasia in later stage can also reduce inflammation, analgesia, and can suppress common pathogen.Confirm that pharmaceutical composition of the present invention has analgesia, antiinflammatory and bacteriostasis.
The specific embodiment
Embodiments of the invention 1: Flos Lonicerae 150g, Fructus Forsythiae 50g, Radix Scrophulariae 150g, Radix Ophiopogonis 50g, Radix Glehniae 53g, Fructus Corni (processed) 50g, Fructus Arctii 75g, Flos Chrysanthemi 18g, Radix Sophorae Tonkinensis 75g, Rhizoma Belamcandae 50g, Semen Sterculiae Lychnophorae 53g, Herba Menthae 18g, Radix Platycodonis 53g, Herba Houttuyniae 25g, Fructus Crataegi 150g, Radix Glycyrrhizae 10g.
Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add 14 times of water gaging distillations 6 hours, and it is standby to extract volatile oil, and debris device is in addition collected, and volatile oil was made clathrate with 6 times of amount beta-cyclodextrins in 2 hours at 50 ℃ of enclose; 13 flavors such as all the other Fructus Arctiis decoct with water three times, and 2 hours for the first time, 1.5 hours for the second time, amount of water is respectively 12 times and 10 times, and collecting decoction filters, the medicinal residues that will extract for the third time behind the volatile oil add, and add 10 times of water gagings, decoct 1 hour, filter, merging filtrate and above-mentioned debris, concentrating under reduced pressure (0.08MPa) to relative density 1.10~1.12 (60 ℃), left standstill 24 hours, get the extractum that supernatant reclaims ethanol and is concentrated into relative density 1.30 (20 ℃), 1 part of qinghuo reagent adds 2 times of amount sucrose, and 1 times of amount dextrin and ethanol are an amount of, granulate, drying, with the beta-cyclodextrin clathrate mixing of volatile oil, system 1000g, packing promptly gets granule.
Embodiments of the invention 2: Flos Lonicerae 50g, Fructus Forsythiae 150g, Radix Scrophulariae 50g, Radix Ophiopogonis 150g, Radix Glehniae 18g, Fructus Corni (processed) 150g, Fructus Arctii 25g, Flos Chrysanthemi 53g, Radix Sophorae Tonkinensis 25g, Rhizoma Belamcandae 150g, Semen Sterculiae Lychnophorae 18g, Herba Menthae 53g, Radix Platycodonis 18g, Herba Houttuyniae 75g, Fructus Crataegi 50g, Radix Glycyrrhizae 30g.
Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add 14 times of water gaging distillations 6 hours, and it is standby to extract volatile oil, and debris device is in addition collected, and volatile oil was made clathrate with 6 times of amount beta-cyclodextrins in 2 hours at 50 ℃ of enclose; 13 flavors such as all the other Fructus Arctiis decoct with water three times, and 2 hours for the first time, 1.5 hours for the second time, amount of water is respectively 12 times and 10 times, and collecting decoction filters, the medicinal residues that will extract for the third time behind the volatile oil add, and add 10 times of water gagings, decoct 1 hour, filter, merging filtrate and above-mentioned debris, concentrating under reduced pressure is (0.08MPa) to relative density 1.10~1.12 (60 ℃), left standstill 24 hours, get the extractum that supernatant reclaims ethanol and is concentrated into relative density 1.30 (20 ℃), 1 part of qinghuo reagent adds 2 times of amount sucrose, 1 times of amount dextrin and ethanol are an amount of, granulate, drying is with the beta-cyclodextrin clathrate mixing of volatile oil, encapsulated, make 1000, packing promptly gets capsule.
Embodiments of the invention 3: Flos Lonicerae 125g, Fructus Forsythiae 75g, Radix Scrophulariae 125g, Radix Ophiopogonis 75g, Radix Glehniae 44g, Fructus Corni (processed) 75g, Fructus Arctii 63g, Flos Chrysanthemi 27g, Radix Sophorae Tonkinensis 63g, Rhizoma Belamcandae 75g, Semen Sterculiae Lychnophorae 44g, Herba Menthae 27g, Radix Platycodonis 44g, Herba Houttuyniae 38g, Fructus Crataegi 125g, Radix Glycyrrhizae 15g.
Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add 14 times of water gaging distillations 6 hours, and it is standby to extract volatile oil, and debris device is in addition collected, and volatile oil was made clathrate with 6 times of amount beta-cyclodextrins in 2 hours at 50 ℃ of enclose; 13 flavors such as all the other Fructus Arctiis decoct with water three times, 2 hours for the first time, 1.5 hours for the second time, amount of water was respectively 12 times and 10 times, collecting decoction, filter, will extract the medicinal residues adding behind the volatile oil for the third time, add 10 times of water gagings, decocted 1 hour, filter, merging filtrate and above-mentioned debris, concentrating under reduced pressure is (0.08MPa) to relative density 1.10~1.12 (60 ℃), left standstill 24 hours, get the extractum that supernatant reclaims ethanol and is concentrated into relative density 1.30 (20 ℃), 1 part of qinghuo reagent adds 2 times of amount sucrose, 1 times of amount dextrin and ethanol are an amount of, granulate, drying is with the beta-cyclodextrin clathrate and the 1% magnesium stearate mixing of volatile oil, tabletting, make 1000, packing promptly gets tablet.
Embodiments of the invention 4: Flos Lonicerae 75g, Fructus Forsythiae 125g, Radix Scrophulariae 75g, Radix Ophiopogonis 125g, Radix Glehniae 27g, Fructus Corni (processed) 125g, Fructus Arctii 38g, Flos Chrysanthemi 44g, Radix Sophorae Tonkinensis 38g, Rhizoma Belamcandae 125g, Semen Sterculiae Lychnophorae 27g, Herba Menthae 44g, Radix Platycodonis 27g, Herba Houttuyniae 63g, Fructus Crataegi 75g, Radix Glycyrrhizae 25g.
Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add 14 times of water gaging distillations 6 hours, and it is standby to extract volatile oil, and debris device is in addition collected; 13 flavors such as all the other Fructus Arctiis decoct with water three times, and 2 hours for the first time, 1.5 hours for the second time, amount of water is respectively 12 times and 10 times, and collecting decoction filters, the medicinal residues that will extract for the third time behind the volatile oil add, add 10 times of water gagings, decocted 1 hour, filter, merging filtrate and above-mentioned debris, concentrating under reduced pressure (0.08MPa) to relative density 1.10~1.12 (60 ℃), left standstill 24 hours, gets supernatant and reclaim ethanol and be concentrated into relative density 1.18 (20 ℃); Other gets sucrose 650g and decocts with water, and after the dissolving, filters, and concentrates and makes syrup, with above-mentioned concentrated solution mixing, boils, and puts coldly, adds antiseptic, above-mentioned volatile oil, tween 80, adjusts volume to 1000ml, packing, and sterilization promptly gets syrup.
Embodiments of the invention 5: Flos Lonicerae 100g, Fructus Forsythiae 100g, Fructus Arctii 50g, Herba Houttuyniae 50g, Herba Menthae 35g, Flos Chrysanthemi 35g, Rhizoma Belamcandae 100g, Radix Sophorae Tonkinensis 50g, Radix Scrophulariae 100g, Radix Platycodonis 35g, Semen Sterculiae Lychnophorae 35g, Radix Ophiopogonis 100g, Radix Glehniae 35g, Fructus Corni (processed) 100g, Fructus Crataegi 100g, Radix Glycyrrhizae 20g.
Fructus Forsythiae, Herba Menthae and Herba Houttuyniae add the water distillation, and it is standby to extract volatile oil, and debris device is in addition collected; All the other Flos Loniceraes, Fructus Arctii, Rhizoma Belamcandae, Radix Sophorae Tonkinensis, Radix Scrophulariae, Radix Platycodonis, Semen Sterculiae Lychnophorae, Radix Ophiopogonis, Radix Glehniae, Fructus Corni (processed), Fructus Crataegi etc. decoct with water, and filter, and the medicinal residues behind the extraction volatile oil are added, decoct with water, filter merging filtrate and above-mentioned debris, concentrating under reduced pressure is got supernatant and is reclaimed ethanol and concentrated, gets supernatant and filters, filtrate adds above-mentioned volatile oil and appropriate amount of auxiliary materials, transfer to 1000ml, filter packing, sterilization, promptly.
Embodiments of the invention 6: Flos Lonicerae 100g, Fructus Forsythiae 100g, Fructus Arctii 50g, Herba Houttuyniae 50g, Herba Menthae 35g, Flos Chrysanthemi 35g, Rhizoma Belamcandae 100g, Radix Sophorae Tonkinensis 50g, Radix Scrophulariae 100g, Radix Platycodonis 35g, Semen Sterculiae Lychnophorae 35g, Radix Ophiopogonis 100g, Radix Glehniae 35g, Fructus Corni (processed) 100g, Fructus Crataegi 100g, Radix Glycyrrhizae 20g.
Fructus Forsythiae, Herba Menthae and Herba Houttuyniae add 14 times of water gaging distillations 6 hours, and it is standby to extract volatile oil, and debris device is in addition collected; All the other Flos Loniceraes, Fructus Arctii, Rhizoma Belamcandae, Radix Sophorae Tonkinensis, Radix Scrophulariae, Radix Platycodonis, Semen Sterculiae Lychnophorae, Radix Ophiopogonis, Radix Glehniae, Fructus Corni (processed), Fructus Crataegis etc. decoct with water three times, 2 hours for the first time, 1.5 hours for the second time, amount of water was respectively 12 times and 10 times, collecting decoction, filter, the medicinal residues behind medicinal residues and the extraction volatile oil merge, and add 10 times of water gagings again, decocted 1 hour, filter, merging filtrate and above-mentioned debris, relative density is 1.10~1.12 when being evaporated to 60 ℃, adding ethanol makes and contains alcohol amount and reach 70%, left standstill 24 hours, relative density is 1.04 when getting supernatant recovery ethanol and being concentrated into 20 ℃, leaves standstill 48 hours, getting supernatant filters, filtrate adds volatile oil and appropriate amount of auxiliary materials, adjusts volume to 1000ml, adjust pH to 5.0~7.0, filter, packing, sterilization, promptly.Oral, every 10ml, one time 1,2~3 times on the one.

Claims (10)

1, a kind of pharmaceutical composition that is used for the treatment of sore throat, it is characterized in that calculating, make this pharmaceutical composition raw materials of effective components and be according to components by weight percent: Flos Lonicerae 50-150g, Fructus Forsythiae 50-150g, Fructus Arctii 25-75g, Herba Houttuyniae 25-75g, Herba Menthae 18-53g, Flos Chrysanthemi 18-53g, Rhizoma Belamcandae 50-150g, Radix Sophorae Tonkinensis 25-75g, Radix Scrophulariae 50-150g, Radix Platycodonis 18-53g, Semen Sterculiae Lychnophorae 18-53g, Radix Ophiopogonis 50-150g, Radix Glehniae 18-53g, Fructus Corni (processed) 50-150g, Fructus Crataegi 50-150g, Radix Glycyrrhizae 10-30g.
2, the pharmaceutical composition of treatment sore throat as claimed in claim 1, it is characterized in that calculating, make this pharmaceutical composition raw materials of effective components and be according to components by weight percent: Flos Lonicerae 100g, Fructus Forsythiae 100g, Fructus Arctii 50g, Herba Houttuyniae 50g, Herba Menthae 35g, Flos Chrysanthemi 35g, Rhizoma Belamcandae 100g, Radix Sophorae Tonkinensis 50g, Radix Scrophulariae 100g, Radix Platycodonis 35g, Semen Sterculiae Lychnophorae 35g, Radix Ophiopogonis 100g, Radix Glehniae 35g, Fructus Corni (processed) 100g, Fructus Crataegi 100g, Radix Glycyrrhizae 20g.
3, the pharmaceutical composition of treatment sore throat as claimed in claim 1 or 2 is characterized in that: described pharmaceutical composition can be made acceptable forms on the pharmaceuticss such as pill, granule, tablet, syrup, mixture, oral liquid, drop pill, capsule, injection, slow releasing preparation or controlled release preparation.
4, the pharmaceutical composition of treatment sore throat as claimed in claim 3 is characterized in that the dosage form that described pharmaceutical composition is made is: oral liquid, syrup, granule, capsule, tablet.
5, the pharmaceutical composition of treatment sore throat as claimed in claim 4 is characterized in that the dosage form that described pharmaceutical composition is made is an oral liquid.
6, the preparation of drug combination method of treatment sore throat as claimed in claim 4 is characterized in that: Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add the water distillation, and it is standby to extract volatile oil, and debris device is in addition collected, and volatile oil is made clathrate; All the other Flos Loniceraes, Fructus Arctii etc. 13 flavor decocts with water, and filters, and will extract the medicinal residues adding behind the volatile oil again, decoct with water, filter merging filtrate and above-mentioned debris, concentrating under reduced pressure, get supernatant and reclaim ethanol and be condensed into extractum, add appropriate amount of auxiliary materials, granulate, dry, with the volatile oil clathrate compound mixing, encapsulated, promptly get capsule.
7, the preparation of drug combination method of treatment sore throat as claimed in claim 4 is characterized in that: Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add the water distillation, and it is standby to extract volatile oil, and debris device is in addition collected; All the other Flos Loniceraes, Fructus Arctii etc. 13 flavor decocts with water, and filters, and the medicinal residues that will extract again behind the volatile oil add, and decoct with water, filter, and merging filtrate and above-mentioned debris, concentrating under reduced pressure is got supernatant and is reclaimed ethanol and concentrated; Other gets sucrose and makes syrup, with above-mentioned concentrated solution mixing, boils, and puts coldly, and appropriate amount of auxiliary materials transfers to 1000ml, packing, and sterilization promptly gets syrup.
8, the preparation of drug combination method of treatment sore throat as claimed in claim 4 is characterized in that: Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add the water distillation, and it is standby to extract volatile oil, and debris device is in addition collected; All the other Flos Loniceraes, Fructus Arctii etc. 13 flavor decocts with water, and filters, and will extract the medicinal residues adding behind the volatile oil again, decoct with water, filter merging filtrate and above-mentioned debris, concentrating under reduced pressure is got supernatant and is reclaimed ethanol and concentrated, gets supernatant and filters, filtrate adds above-mentioned volatile oil and appropriate amount of auxiliary materials, transfer to 1000ml, filter packing, sterilization promptly gets oral liquid.
9, the preparation of drug combination method of treatment sore throat as claimed in claim 8 is characterized in that: Fructus Forsythiae, Herba Menthae and Herba Houttuyniae three flavors add 14 times of water gaging distillations 6 hours, and it is standby to extract volatile oil, and debris device is in addition collected; All the other Flos Loniceraes, 13 flavors such as Fructus Arctii decoct with water three times, 2 hours for the first time, 1.5 hours for the second time, amount of water was respectively 12 times and 10 times, collecting decoction, filter, the medicinal residues behind medicinal residues and the extraction volatile oil merge, and add 10 times of water gagings again, decocted 1 hour, filter, merging filtrate and above-mentioned debris, relative density is 1.10~1.12 when being evaporated to 60 ℃, adding ethanol makes and contains alcohol amount and reach 70%, left standstill 24 hours, relative density is 1.04 when getting supernatant recovery ethanol and being concentrated into 20 ℃, leaves standstill 48 hours, getting supernatant filters, filtrate adds volatile oil and appropriate amount of auxiliary materials, adjusts volume to 1000ml, adjust pH to 5.0~7.0, filter, packing, sterilization promptly gets oral liquid.
10, the method for quality control of the oral liquid of treatment sore throat as claimed in claim 5 is characterized in that this method is the combination of following one or several method:
(1) the present invention is the sepia supernatant liquid, and gas is refrigerant, the sweet little hardship of distinguishing the flavor of;
(2) thin layer of Herba Menthae is differentiated: get 20ml of the present invention, with 60 ~ 90 ℃ petroleum ether 15ml extractions 1 time, extract is concentrated into about 1ml, as need testing solution; It is an amount of that other gets the Mentholum reference substance, makes the solution that every 1ml contains 2mg with ether, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned two kinds of each 2ul of solution, putting respectively on same silica gel G plate, is that benzene-ethyl acetate of 19: 1 is developing solvent with proportioning, launches, take out, dry, spray is vanillin sulphuric acid-ethanol test solution of 2: 8 with proportioning, and 100 ℃ of heating 5min are to clear spot, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on show identical aubergine speckle;
(3) thin layer of Fructus Arctii is differentiated: get 15ml of the present invention, add ammonia 1.5ml jolting mixing, use chloroform extraction three times, and each 25ml, combined chloroform liquid, water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Fructus Arctii control medicinal material 1g, adds ethanol 20ml, and reflux 1h filters, and filtrate evaporate to dryness, residue add ethanol 2ml makes dissolving, in contrast medical material solution; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same above-mentioned silica gel g thin-layer plate, with proportioning is that 10: 1 chloroform-methanol is developing solvent, launches, and takes out, dry, spray is with 10% sulphuric acid ethanol test solution, and 105 ℃ to be heated to speckle colour developing clear; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical blue spot;
(4) thin layer of Radix Glycyrrhizae is differentiated: get 20ml of the present invention, put in the separatory funnel, use water saturation n-butanol extraction 3 times, each 15ml merges n-butyl alcohol liquid, washes with water 3 times, each 20ml, and water bath method, residue add methanol 2ml makes dissolving, as need testing solution; Extracting liquorice control medicinal material 1g in addition, the 40ml that adds diethyl ether, reflux 1h, filter, medicinal residues add methanol 30ml reflux 1h, filter, filtrate evaporate to dryness, residue add water 40ml makes dissolving, uses n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, washes with water 3 times, each 20ml, n-butyl alcohol liquid evaporate to dryness, residue add methanol 5ml makes dissolving, in contrast medical material solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned two kinds of each 2ul of solution, put respectively on same silica gel G plate, with proportioning is 15: 1: 1.5: ethyl acetate-formic acid of 2-glacial acetic acid-water is developing solvent, launches, and takes out, dry, spray is with 10% sulphuric acid ethanol test solution, and 105 ℃ to be heated to the speckle colour developing clear, puts under the 365nm uviol lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the speckle of same color;
(5) thin layer of Radix Platycodonis is differentiated: get 10ml of the present invention, put in the round-bottomed flask, add hydrochloric acid 3ml, water-bath reflux 30 minutes, cool, put in the separatory funnel, extract 3 times the combined ethyl acetate extracting solution with the ethyl acetate jolting, water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Platycodonis control medicinal material powder 1g, adds 7% proportioning and be 1: 3 sulphuric acid alcohol-water mixed liquor 20ml, reflux 3 hours, put coldly, extract 2 times each 20ml with the chloroform jolting, combined chloroform liquid, add water 30ml washing, discard washing liquid, the chloroform solution anhydrous sodium sulfate dehydration, filter, filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; According to Chinese Pharmacopoeia thin layer chromatography test, draw need testing solution 10ul, reference substance solution 5ul, put respectively in same be on the silica gel G plate of adhesive with the sodium carboxymethyl cellulose, be that chloroform-ether of 1: 1 is developing solvent with proportioning, launch, take out, dry; Spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ to be heated to the speckle colour developing clear; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(6) thin layer of Radix Ophiopogonis is differentiated: get 20ml of the present invention, put in the round-bottomed flask, add hydrochloric acid 6ml, water-bath reflux 1 hour, cool, put in the separatory funnel, extract 3 times the combined ethyl acetate extracting solution with the ethyl acetate jolting, water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Other gets control medicinal material 1g Radix Ophiopogonis, adds water 10ml, decocts 30 minutes, filter, filtrate adds hydrochloric acid 2ml, and heating makes and keeps little boiling 10 minutes, cools, put in the separatory funnel, extract 3 times combined ethyl acetate extracting solution, water bath method with the ethyl acetate jolting, residue adds methanol 1ml makes dissolving, in contrast medical material solution; According to Chinese Pharmacopoeia thin layer chromatography test, draw need testing solution 10ul, reference substance solution 5ul, put respectively in same be on the silica gel G plate of adhesive with the sodium carboxymethyl cellulose, be that chloroform-acetone of 4: 1 is developing solvent with proportioning, launch, take out, dry; Spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ to be heated to the speckle colour developing clear; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(7) inspection of relative density: should be not less than 1.03;
(8) inspection of pH value: should be 5.0~7.0;
(9) assay of Flos Lonicerae and Flos Chrysanthemi: with octadecylsilane chemically bonded silica is filler; Proportioning is that the glacial acetic acid solution of 20: 80 methanol-0.5% is a mobile phase; The detection wavelength is 327nm; Theoretical cam curve is pressed the chlorogenic acid peak and is calculated, and should be not less than 2000; Accurate draw 1ml of the present invention, put in the volumetric flask of 25ml, add 50% methanol and be diluted to scale, shake up, as need testing solution; It is an amount of that precision takes by weighing the chlorogenic acid reference substance, adds methanol and make the solution that every ml contains 25ug, in contrast product solution; Accurate respectively reference substance solution and each 5ul of need testing solution of drawing, according to the Chinese Pharmacopoeia high effective liquid chromatography for measuring, the every 10ml of the present invention contains Flos Lonicerae and Flos Chrysanthemi is C with the molecular formula 16H 18O 9The chlorogenic acid meter, should be not less than 3.0mg.
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CN108514588A (en) * 2018-06-26 2018-09-11 桐城市泰安中药材种植专业合作社 A kind of Chinese medicine and preparation method thereof for treating atrophic laryngitis
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CN111888413A (en) * 2020-09-18 2020-11-06 天津中医药大学 Pharmaceutical composition for autumn respiratory diseases
CN115970101A (en) * 2022-12-30 2023-04-18 米乐医疗科技有限公司 Handheld medical ultrasonic atomizer and using method thereof

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