CN101181561A - Chinese medicine as well as preparation method and application thereof - Google Patents
Chinese medicine as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN101181561A CN101181561A CNA2007101911365A CN200710191136A CN101181561A CN 101181561 A CN101181561 A CN 101181561A CN A2007101911365 A CNA2007101911365 A CN A2007101911365A CN 200710191136 A CN200710191136 A CN 200710191136A CN 101181561 A CN101181561 A CN 101181561A
- Authority
- CN
- China
- Prior art keywords
- group
- medicine
- chinese medicine
- preparation
- parts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the traditional Chinese pharmaceutics field and discloses a TCM compound and the preparation method and application. The TCM compound is prepared by the following raw materials according to the weight proportion: periostracum cicadae 400 to 450 parts, baikal skullcap root 200 to 250 parts, earthworm 250 to 300 parts, batryticated silkworm 200 to 250 parts, tatarian aster root 250 to 300 parts, stemona root 400 to 450 parts and fruit of medicine terminalia 200 to 250 parts. The invention has obvious bacteriostatic, antiviral, anti inflammatory, antispasmodic functions as well as relieving cough and asthma and reducing airway responsiveness, which is safe and effective and has low cost, thus the invention can be used for preparing the medicine of relieving cough and asthma as well as antivirus.
Description
Technical field
The invention belongs to field of traditional Chinese medicine pharmacy, relate to a kind of Chinese medicine composition and its production and application.
Background technology
Respiratory tract disease is the clinical common diseases type, usually with symptoms such as cough, expectoration, asthma, inflammation, airway reactivity increase.Cause of disease more complicated, viral infection, bacterial infection, nonspecific inflammation, allergy etc. all can take place, and the treatment measure needs treating both the principal and secondary aspects of a disease.Commonly encountered diseases has bronchitis, pneumonia, bronchial asthma, viral influenza etc., acute bronchitis particularly, its sickness rate is position first of other various respiratory tract diseases, the cough that airway inflammation causes is its cardinal symptom, can increase because of the airway reactivity that inflammation causes simultaneously, and make respiratory symptom continue not understand, cause clinical treatment more thorny.Have plurality of Chinese and Western medicine in the market, all give priority at different aspect, the part drug price is higher, causes clinical practice to be difficult to popularize.
Summary of the invention
The purpose of this invention is to provide a kind ofly have cough-relieving, relieving asthma, the Chinese medicine composition of antiinflammatory, antibacterial, antivirus action.
Another object of the present invention provides the preparation method of above-mentioned Chinese medicine composition.
A further object of the invention provides the application of above-mentioned Chinese medicine composition in the preparation cough suppressing medicine.
The objective of the invention is to realize by following technical measures:
A kind of Chinese medicine composition, its prescription contain following bulk drugs material:
Periostracum Cicadae 400-450 part, Radix Scutellariae 200-250 part, Pheretima 250-300 part, Bombyx Batryticatus 200-250 part, Herba Schizonepetae 200-250 part, Radix Asteris 250-300 part, Radix Stemonae 400-450 part, Fructus Chebulae 200-250 part.
Described Chinese medicine composition, its prescription contain following bulk drugs material:
414 parts of Periostracum Cicadaes, 230 parts of Radix Scutellariaes, 276 parts of Pheretimas, 230 parts of Bombyx Batryticatus, 230 parts of Herba Schizonepetae, 276 parts of Radix Asteriss, 414 parts of the Radixs Stemonae, 230 parts of Fructus Chebulaes.
Described Chinese medicine composition, its dosage form are tablet, granule, capsule, pill, oral liquid, injection.
The preparation method of described Chinese medicine composition comprises the following steps:
A. get raw medicinal material by prescription, wherein Herba Schizonepetae adds suitable quantity of water and soaks after 1～3 hour, extracts volatile oil 2～4 hours, medicinal residues I and the residual liquid usefulness of purchasing in addition;
B. Periostracum Cicadae, Radix Scutellariae, Pheretima, Radix Asteris, the Radix Stemonae, Fructus Chebulae to add an amount of concentration be 60～80% alcohol reflux 2～4 times, each 1～3 hour, filter, medicinal residues II and filtrate, filtrate merges, and reclaims ethanol to there not being the alcohol flavor, medicinal liquid A is standby;
C. the medicinal residues I of medicinal residues II and step a and residual liquid merging adds Bombyx Batryticatus and suitable quantity of water, decocts 2～4 times, and each 2-3 hour, merging filtrate filtered, and filtrate decompression is concentrated into 70 ℃ of relative densities and is about 1.2～1.4, merges with medicinal liquid A, gets medical liquid B;
D. volatile oil and medical liquid B are merged, add liquid preparation adjuvant commonly used and make liquid preparation by the liquid preparation common process; Perhaps
Volatile oil is added 30～50 times of water gagings, and 3～5 times of amount beta-schardinger dextrin-s grind enclose with colloid mill, filter 65～75 ℃ of oven dry of clathrate; In addition medical liquid B is carried out drying, be ground into fine powder; Add the corresponding conventional adjuvant according to required solid preparation in fine powder, add clathrate, common process is made solid preparation.
The preparation method of described Chinese medicine composition, wherein step e is: fine powder adds an amount of dextrin mixing, with 80% ethanol system granule, in the clathrate adding granule with step b gained, mixing, granule is made in packing.
The application of described Chinese medicine composition in the preparation cough suppressing medicine.
The application of described Chinese medicine composition in the preparation antiviral drugs.
The application of described Chinese medicine composition in the preparation suppressing panting calming medicine.
The application of described Chinese medicine composition in the preparation antibacterial medicines.
The application of described Chinese medicine composition in the preparation anti-inflammatory drug.
Beneficial effect of the present invention:
Chinese medicine composition dispelling wind heat provided by the invention, lung heat clearing network, declare respectful cough-relieving, have effects such as significantly antibacterial, antiviral, antiinflammatory, spasmolytic, relieving cough and asthma, reduction airway reactivity, there is not obvious acute toxic reaction, there are not obvious cumulative toxicity and retardance toxic action yet, safe and effective, good stability, cheap, for extensive patients provides more choices.Preparation method provided by the invention is simple, and cost is low.
One, the pharmacodynamic experiment of Chinese medicine composition of the present invention:
Experiment 1: medicine of the present invention draws the influence of the effect of coughing to mice ammonia
Experiment material:
1 is subjected to the reagent thing: medicine of the present invention (pressing embodiment 1 preparation) hereinafter to be referred as Periostracum Cicadae, down together, produce lot number 980320 by the special pharmaceutical factory of Henan Province's Olympic.Specification: 9 bags/box, 10 gram/bags.Clinical consumption: every day 3 times, each 1 bag.Every gram finished product is equivalent to crude drug in whole 2.30g approximately.When making granule, added dextrin, so need not add other suspending agent, during use with distilled water be made into 40%, 20%, 10% 3 kind of concentration solution.
2 positive control drugs: magical Folium Eriobotryae cough-stopping granule (being called for short the Folium Eriobotryae cough-relieving), Guizhou Shenqi Pharmaceutical Co., Ltd produces, lot number 98090601 (adult's consumption 5g/ people/time, 3 times/day), be made into 20% concentration with distilled water during use.
3 reagent: ammonia, Kaifeng chemical reagent factory produces lot number: 9700108.
4 animals: Kunming mouse, purchase Experimental Animal Center in Henan Province.The quality certification number: the moving word 99007 of doctor.
Experimental technique:
1, grouping and administration: get 50 of healthy Kunming mouses, body weight 18～20g, male and female half and half are divided into 5 groups at random, gastric infusion, once a day, continuous three days.
Blank group: normal saline, 10ml/kg; Positive controls: Folium Eriobotryae cough-stopping granule, 2g/kg; Periostracum Cicadae high dose group: 4g/kg; Dosage group: 2g/kg in the Periostracum Cicadae; Periostracum Cicadae low dose group: 1g/kg.
2, ammonia draws and coughs and index determining: the last administration placed respectively in the glass bell jar of 4L after 1 hour, with nebulizer 14% ammonia atomization was imported 5 seconds of bell jar, the incubation period (by spraying into to the mouse cough required time) of record mouse cough.
3, statistical method: relatively t check between the result organizes.
Experimental result: each treated animal is after the smoked suction of ammonia, and medicine group of the present invention and magical Folium Eriobotryae cough-stopping granule group are than the normal saline group, and cough latent period obviously prolongs (table 1).
Table 1 medicine of the present invention is to the influence of ammonia induced mice cough latent period
| Grouping | Dosage | Cough latent period (S) |
| Dosage group Periostracum Cicadae small dose group Folium Eriobotryae cough-stopping granule group in the normal saline group Periostracum Cicadae high dose group Periostracum Cicadae | 4g/kg 2g/kg 1g/kg 2g/kg | 24.6±5.1 47.3±6.7** 41.2±5.5** 37.1±4.6** 35.8±4.7** |
The normal saline group relatively.
**P＜0.01。
Conclusion: this experiment utilizes ammonia to bring out mouse cough, observes the antitussive action of medicine of the present invention, and the result shows, medicine of the present invention can obviously prolong mice ammonia and draw and cough incubation period, with the blank group significant difference is arranged relatively.
Experiment 2, medicine of the present invention draw the influence of the effect of coughing to the Cavia porcellus citric acid
Experiment material:
1 is subjected to the reagent thing: medicine of the present invention, and the same.
2 positive control drugs: magical Folium Eriobotryae cough-stopping granule, the same.
3 reagent: sodium citrate, Kaifeng chemical reagent factory produces lot number: 950910.
4 animals: Cavia porcellus, body weight 200～250g, male and female half and half are provided by Henan Province's Experimental Animal Center.
Experimental technique:
1, animal screening: get Cavia porcellus and place respectively in the airtight bell jar of 4L, in the sodium citrate importing bell jar with nebulizer atomizing 17.5%, atomized 1 minute, the cough number of times of Cavia porcellus is less than person's reject 10 times with number of times in the record 5min.
2, grouping and administration: get 50 of qualified Cavia porcelluss, male and female half and half are divided into 5 groups at random, gastric infusion, once a day, continuous three days.
Blank group: normal saline, 10ml/kg; Positive controls: Folium Eriobotryae cough-stopping granule, 2g/kg; Periostracum Cicadae high dose group: 4g/kg; Dosage group: 2g/kg in the Periostracum Cicadae; Periostracum Cicadae low dose group: 1g/kg.
3, citric acid draws and coughs and index determining: last administration 1 hour, and drew in 60 seconds with the sodium citrate atomizing and to cough, write down the cough latent period and the number of times of coughing in 5 minutes.
4, statistical method: relatively t check between the result organizes.
Experimental result: medicine of the present invention can obviously prolong incubation period and reduce the cough number of times guinea pig cough due to the citric acid, sees Table 2.
Table 2 medicine of the present invention draws the effect of coughing to citric acid
| Grouping | Dosage | Incubation period (second) | The cough number of times (inferior/5min) |
| The low dose of Folium Eriobotryae cough-stopping granule of dosage Periostracum Cicadae in the heavy dose of Periostracum Cicadae of normal saline group Periostracum Cicadae | 4g/kg 2g/kg 1g/kg 2g/kg | 77.6±20.1 167.9±27.4** 153.2±26.1** 131.9±28.5 148.8±26.9** | 19.2±3.4 10.1±2.6** 11.5±2.7** 12.7±2.9 10.6±2.9** |
Compare with the normal saline group,
*P＜0.01.
Conclusion: this experiment utilizes citric acid to bring out the guinea pig cough, observes the antitussive action of medicine of the present invention, and the result shows that the obvious prolonged guinea pig citric acid of medicine energy of the present invention draws coughs incubation period, significantly reduces the cough number of times, with the blank group significant difference is arranged relatively.
Experiment 3: medicine of the present invention draws the influence of coughing to electricity irritation cat superior laryngeal nerve
Experiment material:
1 is subjected to the reagent thing: medicine of the present invention, and the same.Be made into 30%, 15% and 7.5% 3 kind of concentration during experiment.
2 positive control drugs:
Magical Folium Eriobotryae cough-stopping granule: the same, be made into 20% concentration with deionized water during use.
Anticol (compound codeine phosphate oral liquid), per 5 milliliters of phosphoric acid contain codeine 5mg, ephedrine hydrochloride 4mg, chlorphenamine 1mg, ammonium chloride 110mg, the Shenzhen City Pharmaceutical Factory produces, lot number 981072, clinical adult's consumption 10-15ml/ time, 3 times/day.This medicine is clinical Western medicine antitussive commonly used.
3 instruments:
3.1SEN-7103 the type electronic stimulator, Japanese NIHOW KOHDEN produces.
3.2LMS-2B physiograph, Chengdu Instruement Factory produces.
4 animals: the hybrid domestic cat, body weight 2.38 ± 0.33kg, male and female half and half, Henan Prov. Inst. of Chinese Medicine ﹠ Pharmacology's animal center provides.
The experiment grouping:
1, medicine of the present invention, high dose group 3g/kg (in patent medicine, medicine 30g adding distil water is to 100ml, 10mi/kg body weight ig); In dosage group 1.5g/kg (in patent medicine, medicine 15g adding distil water is to 100ml, 10ml/kg body weight ig); Low dose group 0.75g/kg (in patent medicine, medicine 7.5g adding distil water is to 100ml, 10ml/kg body weight ig).
2, anticol, 4.5mg/kg (in codeine phosphate content), medicinal liquid 45ml adding distil water be to 100ml, 10ml/kg body weight ig.
3, magical Folium Eriobotryae cough-stopping granule, 1.8g/kg, medicine 18g adding distil water be to 100ml, 10ml/kg body weight ig).
4, solvent control group, distilled water 10ml/kg, ig.
Experimental technique:
1, gets healthy cat, weigh, with pentobarbital sodium 30mg/kg intraperitoneal injection of anesthesia; back of the body position is fixed on the operating-table; along neck midline incision skin, separate subcutaneous tissue, expose thyroid cartilage; find out a side vagus nerve; find out the knot neuroganglion along the vagus nerve head-end, promptly visible superior laryngeal nerve is told by nerve node, carefully isolates superior laryngeal nerve (not injured nerve) then by last protection electricity level; and drip several drop of liquid paraffin at the electrode place, with anti-drying.
2, expose a part of rectus abdominis m. in abdominal incision skin, stitch a silk thread on muscle, the other end is fixed on the tension transducer, with monitor record cat status of cough.
3, regulate electronic stimulator, have related parameter as follows: the wide 0.5ms of ripple, pulse frequency 50 times/second, in 5 seconds of each stimulus duration, the adjacent twice stimulus intervals time is not less than 5 minutes.Regulating stimulates output voltage to increase progressively from low to high, measure when administration is preceding to stimulate superior laryngeal nerve and cause that the voltage threshold of cough is the cough threshold value of this cat (being as the criterion so that double stimulus threshold is constant), then once, changes of threshold situation after the mensuration administration to the cat gastric infusion.
4, observation index: electroshock threshold comprises the preceding threshold value of administration, max-thresholds after the administration, and difference before and after calculating, raising rate etc.
Threshold value before max-thresholds-administration after threshold value raising difference (V)=administration
The result: experimental result shows: medicine height of the present invention, middle dosage group can obviously improve to cause coughs the stimulation voltage threshold value, and anticol also has same purpose, sees Table 3.
Table 3 medicine of the present invention causes the influence of coughing voltage threshold (n=10, X ± SD) to electricity irritation cat superior laryngeal nerve
| Group | Dosage (g/kg) | Threshold value (V) before the administration | Max-thresholds after the administration (V) | Difference (V) before and after the administration | Threshold value raising rate (%) | Threshold value begins the rising time (min) |
| The magical Folium Eriobotryae of blank medicine of the present invention medicine of the present invention medicine anticol of the present invention | 3 1.5 0.75 0.84 1.8 | 0.58±0.23 0.58±0.29 0.59±0.21 0.54±0.21 0.62±0.25 0.51±0.30 | 0.80±0.26 3.39±1.03 **△△ 2.01±0.30 **△△ 0.79±0.28 5.72±1.80 **△△ 1.02±0.49 △ | 0.22±0.10 2.81±0.87 1.42±0.27 ** 0.25±0.14 5.10±1.84 ** 0.51±0.37 | 41.7±25.4 582.9±302.6 ** 275.5±125.3 50.3±30.8 1003.6± ** 127.3±128.9 | 91.1±56.1 80.0±220.8 98.0±35.2 77.0±231.6 48.6±15.3 71.9±37.5 |
Annotate: with before the administration relatively:
△P＜0.05,
△ △P＜0.01; Compare with the blank group:
*P＜0.05,
*P＜0.01.
Conclusion: this experiment utilizes electricity irritation cat superior laryngeal nerve to draw the method for coughing, observe medicine antitussive action of the present invention, the result shows, medicine 3g/kg of the present invention, 1.5g/kg, three dosage groups of 0.75g/kg are respectively to the cat gastric infusion, but 3g/kg and 1.5g/kg obviously improve electricity irritation cat superior laryngeal nerve causes the voltage threshold of coughing, and with the dosage increase, effect strengthens.The result shows that medicine of the present invention has the central antitussive effect to cat.
Experiment 4: medicine of the present invention is to the influence of guinea-pig isolated tracheal smooth muscle
Experiment material:
1, medicine of the present invention and magical Folium Eriobotryae cough-stopping granule, the same, be made into 40% and 20% concentration during use respectively with normal saline.
2, histamine phosphate, lot number: 960711.Shanghai Biochemical Research institute of Chinese Academy of Sciences product.
3, acecoline, lot number: 971125, Shanghai reagent three factory's products.
4, animal: the Cavia porcellus that grows up, male and female are regardless of, and body weight 367 ± 42g is provided by Henan Province's Experimental Animal Center.
5, instrument, isolated organ side are decided instrument.The DC-001 type, analytical tool factory in Nanjing produces.
Experimental technique:
Get healthy guinea pig, after beating the head of fiercelying attack and cause dusk with wood, the femoral artery blood-letting causes death, cut off skin of neck rapidly, separate trachea, from the thyroid cartilage to cut down to tracheorrhaphy fork whole piece trachea, (0 ℃ of nutritional solution fills O in advance to put into the cultivation vessel that fill the Krebs nutritional solution
2Saturated), wipe out trachea connective tissue on every side, trachea is cut into the wide spiral bar of about 3mm.Put into the isolated organ analyzer, add nutritional solution, ventilation (95%O
2And 5%CO
2).Allow trachea balance 120min in nutritional solution, change three times nutritional solution.Connect the monitor power supply, write down one section normalized curve after, follow these steps to again carry out.
(1) adds the 0.2ml of 0.01% histamine phosphate (His), when waiting the peak to occur, observe adding accumulative total respectively and add
Medicine of the present invention (0.4g/ml) 0.2ml, 0.4ml, 0.8ml; Magical Folium Eriobotryae cough-stopping granule (0.2g/ml) 0.2ml, 0.4ml, 0.8ml, blank; Accumulative total adds normal saline 0.2ml, smooth muscle contraction situation behind 0.4ml, the 0.8ml.
(2) add 0.05% acetylcholine (Ach) 0.2ml, when waiting the peak to occur, observe medicine respectively with (1), and record smooth muscle contraction situation.
The result: medicine of the present invention has obvious antagonism to spasm due to guinea-pig isolated tracheal smooth muscle His and the Ach.(table 4,5)
Table 4 is sloughed off cough-stopping granule guinea-pig isolated tracheal smooth muscle His is caused influence after the convulsion
| Group | State to smooth muscle behind the His | The state of smooth muscle after the administration | ||
| 0.2ml | 0.4ml | 0.8ml | ||
| Blank group Periostracum Cicadae group Folium Eriobotryae cough-relieving group | 70.7±6.9 70.8±6.4 70.6±6.8 | 70.1±6.8 55.8±6.4** 62.2±6.9 | 68.5±7.46 29.8±5.4** 49.7±7.7** | 66.3±7.89 23.3±7.1** 45.3±8.3** |
With comparison before the administration, * * P＜0.01
Table 5 medicine of the present invention causes influence after the convulsion to guinea-pig isolated tracheal smooth muscle Ach
| Group | Put down after giving Ach | The state of smooth muscle after the administration |
| The state of sliding flesh | 0.2ml | 0.4ml | 0.8ml | |
| Blank group Periostracum Cicadae group Folium Eriobotryae cough-relieving group | 185.5±12.5 184.5±12.4 186.3±11.6 | 184.6±12.6 171.5±13.0** 137.1±13.5** | 181.6±12.1 162.3±13.9** 116.4±13.5** | 179.8±11.9 131.3±17.9** 110.1±14.5** |
With comparison before the administration,
*P＜0.01.
Conclusion: medicine of the present invention causes convulsion to guinea-pig isolated tracheal smooth muscle histamine (His) and has spasmolysis: after acetylcholine (Ach) is caused convulsion, tangible spasmolysis is arranged also.
Experiment 5: the antiinflammatory action of medicine of the present invention
Experiment material:
1, medicine of the present invention, the same.
2, animal: Kunming mouse, male, body weight 25～30g is provided by Henan Province's Experimental Animal Center.The quality certification number: the moving word 99007 of doctor.
3, Oleum Tiglii causes scorching liquid: Oleum Tiglii 2%, and ether 78%, dehydrated alcohol 20%, mixing is put in the port grinding bottle, and 5 ℃ of refrigerators are preserved standby.
4, aspirin, the Zhengzhou chemical pharmaceutical factory medicine of supplying raw materials is made into 20mg/ml with 1% dextrin solution during use, i.e. 2% concentration.
Experimental technique:
60 of mices are selected in experiment for use, be divided into 6 groups at random: (1) blank group: the heavy dose of group of Periostracum Cicadae ig normal saline 10ml/kg:(2): ig Periostracum Cicadae 4g/kg, (3) dosage group in the Periostracum Cicadae: ig Periostracum Cicadae 2g/kg, (4) Periostracum Cicadae small dose group: ig Periostracum Cicadae 1g/kg, (5) the magical Folium Eriobotryae cough-stopping granule of magical Folium Eriobotryae cough-stopping granule group: ig 2.0g/kg, (6) aspirin group, ig aspirin 200mg/kg.Each treated animal, every day ig once, totally 6 days.Behind the 6th day administration 30min, ear two sides, every mice left side is evenly coated Oleum Tiglii and is caused scorching liquid 0.5ml, and after 4 hours, mice takes off vertebra puts to death, and lays two auricles with 8mm diameter card punch in same area, weighs, and obtains two auricle differences, calculates suppression ratio by following formula:
The result: the results are shown in Table 6, large, medium and small dosage group of Periostracum Cicadae and Folium Eriobotryae cough-stopping granule group and normal saline group compare, and mice two ear weight differences all decrease, and wherein the heavy dose of group effect of Periostracum Cicadae is the strongest.
Table 6: medicine of the present invention is to the influence of mice ear
| Group | The example number | Dosage g/kg | Difference | Average suppression ratio (%) |
| Dosage group Periostracum Cicadae small dose group in the heavy dose of group of the blank group aspirin matched group Folium Eriobotryae cough-relieving matched group Periostracum Cicadae Periostracum Cicadae | 10 10 10 10 10 10 | 0.2 2 4 2 1 | 18.9±3.8 10.2±2.3** 16.7±3.0 15.3±2.4* 16.7±2.8 16.8±2.5 | 46.0％ 11.6％ 19.0％ 11.6％ 11.1％ |
Annotate: compare with model control group,
*P＜0.05,
*P＜0.01
Conclusion: medicine of the present invention has tangible antiinflammatory action.
Experiment 6: medicine of the present invention is to immune influence
Experiment material:
1, medicine of the present invention, the same;
2,2, the 4-dinitrochlorobenzene, lot number: 970611, Shanghai reagent one factory;
3, azovan blue, lot number: 950415, Shanghai chemical reagent purchasing and supply station;
4, chicken erythrocyte suspension, conventional chicken wing vein is got blood, puts 4 ℃ of preservations of 2 times of A Shi liquid;
5, Dou Shi reagent, sodium bicarbonate 1.0g, potassium cyanide 0.05g, high-potassium ferricyanide 0.2g, adding distil water is to 1000ml;
6, complement preparation: fresh guinea pig serum, with 1: 10 diluted for use of normal saline.
7, animal: Kunming mouse, male and female half and half, body weight 18～22g; Provincial Medicine Research Institute, effluent south Animal House provides.The quality certification number: the moving word 99012 of doctor.
Experimental technique:
1, to 2, the influence of delayed skin hypersensitivity (DTH) due to the 4-dinitrochlorobenzene (DNCB)
50 of mices are selected in experiment for use, be divided into 5 groups at random, grouping and medication see Table 7, drip 2ul/ sensitization of 0.5g/ml DNCB liquid in the depilation back down in mouse carotid, administration successive administration on the same day dripped 0.025g/ml DNCB liquid 20ul/ and only attacks after 10 days on mouse web portion depilation skin.Iv 1mg/ml azovan blue 10mg/kg puts to death animal after 24 hours behind the 30min, gets abdominal part indigo plant and dyes skin, shreds and puts in the test tube, soaks 24 hours with 1: 1 acetone normal saline 5ml, gets supernatant colorimetric (λ=610nm).
The result: medicine of the present invention has no significant effect the intensity of mouse DTH reaction, and administration group OD value is lower than matched group (table 7).
Table 7 medicine of the present invention is to the influence of DNCB inducing mouse DTH reaction
| Group | Dosage g/kg/d | OD×100 |
| Dosage group Periostracum Cicadae small dose group Folium Eriobotryae cough-relieving group in the heavy dose of group of the blank group Periostracum Cicadae Periostracum Cicadae | 10ml/kg 4g/kg 2g/kg 1g/kg 2g/kg | 8.03±1.12 7.25±0.89 7.68±0.89 7.99±0.85 7.67±1.14 |
Annotate: compare with the blank group,
*P＜0.05
2, medicine of the present invention is to the influence of serum hemolysin
Select 50 of Kunming mouses for use, be divided into 5 groups at random, grouping and medication see Table 8, the continuous ig administration of each treated animal 7 days, in experiment ip 2% chicken red blood cell suspension 0.2ml/ on the same day only.Extract eyeball after 7 days and only get blood 20ul/, add in the 1ml normal saline, every pipe adds 5% chicken red blood cell 0.5ml, put 37 ℃ of water-bath 30min, the refrigerator cessation reaction, centrifugal, 2500rpm 5 minutes, get supernatant 1ml and add after 3ml Dou Shi reagent leaves standstill 10min 722 spectrophotometer 540nm place colorimetrics.
The result: the administration treated animal compares OD value there was no significant difference (table 8) with blank group.
The influence that table 8 medicine of the present invention generates the mice serum hemolysin
| Group | Dosage g/kg/d | OD×100 |
| Dosage group Periostracum Cicadae small dose group Folium Eriobotryae cough-relieving group in the heavy dose of group of the blank group Periostracum Cicadae Periostracum Cicadae | 10ml/kg 4g/kg 2g/kg 1g/kg 2g/kg | 1.20±0.31 0.98±0.19 1.05±0.26 1.02±0.22 1.08±0.18 |
Conclusion: medicine of the present invention generates to DNBC inducing mouse DTH and to the mice serum hemolysin and has no significant effect, and has only reduction trend.
Experiment 7: the inside and outside bacteriostatic experiment of medicine of the present invention
Experiment material:
1, laboratory animal: Kunming mouse, body weight 14 ± 1g, male and female dual-purpose.Provide by Chinese Academy of Medical Sciences animal cultivation field.The quality certification number: SCXK11-00-0006.
2, be subjected to the reagent thing: medicine of the present invention, the same.
3, positive drug: ciprofloxacin injection, Bayer A.G makes, lot number: 960701, be diluted to the original liquid that contains 0.2mg/ml with broth bouillon during experiment in vitro and be used for experiment; The ciprofloxacin sheet, make the Tianjin Central Pharmaceutical Co., Ltd, lot number: 010336, press clinical equivalent dosage gastric infusion during experiment.
4, bacterial isolates: staphylococcus aureus (260032-18); Staphylococcus albus (26101); Beta hemolytic streptococcus (32,172 10); Pneumobacillus (11 14); Escherichia coli (44,113 23); Bacillus pyocyaneus (10,211 55); Bacillus proteus (49,101 1); Block its coccus (29108); Gonococcus (29106).Examine and determine Institute of Medicinal Biological Technique, Beijing in one's power available from the Ministry of Public Health pharmaceutical biological product respectively, be clinical isolates strain or type strain in half a year.
5, broth bouillon: Ministry of Public Health pharmaceutical biological product calibrating produce lot number: 980226.
6, the disposable culture plate in 24 holes.37 ℃ of incubators.
Method and result:
1, to the protective effect of beta hemolytic streptococcus induced mice death
1.1 determining of infecting mouse minimum lethal dose (MLD)
Beta hemolytic streptococcus is carried out 10 with normal saline
5-10
9After the dilution of individual bacterium/ml, injection is infected to mouse peritoneal.Every 0.5ml, each dilution factor infects 10, respectively organizes the death condition of mice after record infects, and observes continuously 7 days.Dilution factor that will mortality of mice reaches more than 80% in 3 days is decided to be minimum lethal dose.Through observing repeatedly, beta hemolytic streptococcus is 10 in this experiment
8During the dilution of individual bacterium/ml, cumulative mortality can reach more than 80% in the mice 3 days, so it is decided to be minimum lethal dose, is used for infection animal.
1.2 protective effect to dead mouse
Get 100 of mices, body weight 14 ± 1g is divided into 5 groups at random by body weight, and experimental group gives medicine 3.0g of the present invention, 2.0g, 1.0g patent medicine/kg/d respectively; Ciprofloxacin sheet group 0.143g/kg/d; The bacterial infection matched group gives the distilled water with volume.Continuous three days, got in the 4th day and to increase 18 hours beta hemolytic streptococcus bacterium liquid of bacterium and (contain 10
8Individual bacterium/ml), 0.5ml/, lumbar injection is made lethal hit, continues administration after the infection again two days.Every day, record infected back animal dead number, in continuous 1 week, calculated mortality rate, protective rate and increase in life span, with X
2And statistical procedures is carried out in the t check.The results are shown in Table 9,10.
Table 9 medicine of the present invention causes the influence of mouse death rate to beta hemolytic streptococcus
| Group | Dosage g/kg/d | Number of animals (only) | Death toll (only) | Mortality rate (%) | Protective rate (%) |
| Bacterial infections ciprofloxacin sheet Periostracum Cicadae granule (greatly) Periostracum Cicadae granule (in) Periostracum Cicadae granule (little) | 0.143 3.0 2.0 1.0 | 20 20 20 20 20 | 15 2 9 13 14 | 75 10 45 65 70 | 86.67** 40.00 13.00 6.67 |
Compare with bacterial infections:
*P＜0.01
Table 10 medicine of the present invention causes the influence of mice time-to-live to beta hemolytic streptococcus
| Group | Dosage g/kg/d | Number of animals (only) | Average survival natural law | Increase in life span (%) |
| Bacterial infections ciprofloxacin sheet Periostracum Cicadae granule (greatly) Periostracum Cicadae granule (in) Periostracum Cicadae granule (little) | - 0.143 3.0 2.0 1.0 | 20 20 20 20 20 | 3.1±2.51 6.6±1.27** 4.8±2.62* 3.7±2.59 3.6±2.56 | 112.90 54.83 19.35 16.12 |
Compare with bacterial infections:
*P＜0.01
*P＜0.05
Table 9,10 results show: in the mouse infection antibacterial 7 days, the death toll of medicine 3.0g/kg/d dosage group mice of the present invention infects matched group and reduces (protective rate is 40%) relatively, but no significant difference statistically.But the average survival natural law of mice infects matched group and obviously prolongs, and statistics has significant difference (P＜0.05).Show that medicine of the present invention causes dead mouse to the beta hemolytic streptococcus infection certain protection effect is arranged when this dosage.
2. the external bacteriostatic experiment of medicine of the present invention
After will being subjected to the reagent thing to carry out 1: 5～1: 160 times doubling dilution with broth bouillon, add on the 24 porocyte culture plates, each dilution factor is respectively established 2 holes, every hole adds medicinal liquid culture medium 1.0ml, the bacterium liquid 0.1ml that adds 105 bacterium/ml again, put in 37 ℃ of incubators and cultivated 24 hours, observe bacterial growth situation in each hole.Establish antibacterial contrast and positive control drug contrast simultaneously.The results are shown in Table 11.
Table 11: the external bacteriostatic experiment of medicine of the present invention
| Strain | Minimum inhibitory concentration MIC (mg/ml), inhibitory potency | ||||
| Title | Bacterium number | Medicine of the present invention | Ciprofloxacin | The antibacterial contrast | |
| Its coccus gonococcus bacillus pyocyaneus of pneumobacillus beta hemolytic streptococcus staphylococcus aureus Staphylococcus albus degeneration bacillus escherichia coli card | 14 11 10 32172 26003 2-18 26101 1 49101 23 44113 29108 29106 55 10211 | 6.25 6.25 12.5 12.5 6.25 6.25 12.5 6.25 6.25 25 25 25 12.5 6.25 6.25 | 1∶40 1∶40 1∶20 1∶20 1∶40 1∶40 1∶20 1∶40 1∶40 1∶10 1∶10 1∶10 1∶20 1∶40 1∶40 | - - - - - - - - - - - - - - - | + + + + + + + + + + + + + + + |
+: representing has bacterial growth-: represent no bacterial growth
2.2 the result shows: after cultivating in 24 hours, the antibacterial control wells all has bacterial growth.Medicine of the present invention all has in various degree inhibitory action to 9 kinds of antibacterials being tried, 15 bacterial strains, and between 6.25～25mg/ml, inhibitory potency is respectively between 1: 10～1: 40 respectively for minimum inhibitory concentration.Ciprofloxacin growth to external antibacterial when institute's amount of reagent all has the obvious suppression effect.
Brief summary: this laboratory observation the inside and outside bacteriostasis of medicine of the present invention, the result shows: medicine of the present invention can obviously prolong the existence natural law of mice in the dead protection experiment to the beta hemolytic streptococcus induced mice, the death toll of mice has the trend of minimizing; At experiment in vitro, medicine of the present invention all has in various degree inhibitory action to 9 kinds of antibacterials being tried, 15 bacterial strains, and minimum inhibitory concentration is between 6.25～25mg/ml, and inhibitory potency is 1: 10～1: 40.Illustrate that medicine of the present invention all has tangible bacteriostasis in testing in vivo and in vitro.
Experiment 8: medicine interior resisting virus test of the present invention
Experiment material:
1, animal: mice, body weight 12-15g, male and female half and half are planted by Switzerland.Provide the quality certification number by Institute of Experimental Animals, Chinese Academy of Medical Sciences breeding farm: 01-3001.
2, virus: influenza virus A-prime Mus lung adapted strain FM1 ,-60 ℃ of cryogenic refrigerators are preserved standby.
3, immune serum: with the FM1 virus immunity rabbit that chick embryo allantoic liquid goes down to posterity, obtain high immune serum of tiring, frozen standby in-60 ℃ of refrigerators.
4, traget antibody: goat anti-rabbit igg-FITC, Huamei Bio-Engrg Co., produces, and-20 ℃ of preservations are standby.
5, be subjected to the reagent thing: medicine of the present invention, the same.During experiment by 11,5.5, the administration of 2.75g/kg/d mouse stomach.
6, positive control drug: magical Folium Eriobotryae cough-stopping granule, Guizhou Shenqi Pharmaceutical Co., Ltd produces, lot number: 98040201; Virazole: Hubei Province's institute of Pharmaceutical Industry is produced, and is crude drug.
Method and result:
1, to the inhibitory action of mice influenza virus property pneumonia
Get 70 of mices and be divided into 7 groups at random by body weight.Give medicine of the present invention above-mentioned three dosage respectively; Virazole (0.07g/kg/d) group; Magical Folium Eriobotryae cough-stopping granule group (2.75g/kg/d); Viral infection matched group and intact animal's matched group.Except that the normal control group, mice is slightly anaesthetized with ether, with 15 LD
50Influenza virus drop nose infects, every 0.05ml.Begin gastric infusion the previous day from infecting, continuous 5 days, the virus control group was irritated stomach to wait capacity distilled water.Dissected after taking by weighing the mice body weight on the 6th day, the perusal pulmonary lesion, the degree of record pulmonary liver sample consolidation is won full lung and is weighed, and calculates the lung exponential quantity one by one, and obtains lung index suppression ratio.
Lung index=[heavy (the g)/body weight (g) of lung] * 100
Statistical procedures is carried out in the t check between employing group as a result.See Table 12.
Table 12 medicine of the present invention is to the inhibitory action of mice influenza virus property pneumonia
| Group | Dosage g/kg/d | Mus number (only) | The lung exponential quantity (X ± SD) | Suppression ratio (%) |
| Virus control group normal control papova azoles group Folium Eriobotryae groups of grains Periostracum Cicadae granule (greatly) Periostracum Cicadae granule (in) Periostracum Cicadae granule (little) | - - 0.07 2.75 11 5.5 2.75 | 10 10 10 10 10 10 10 | 1.618±0.289 1.111±0.043** 1.314±0.193* 1.352±0.208* 1.253±0.159** 1.407±0.127* 1.584±0.334 | 0 31.33 18.78 16.42 22.58 13.05 0.106 |
Compare with the virus control group:
*P＜0.01,
*P＜0.05
The result shows: the lung exponential quantity of the big or middle dosage treated animal of Periostracum Cicadae all is lower than the virus control group, with the virus control group significant difference is arranged relatively.Show that the mice pneumonia that Periostracum Cicadae causes influenza virus 11, during 5.5g/kg/d dosage has the obvious suppression effect.
2, to the influence of proliferation of influenza virus amount in the mouse lung
Removing the viral infection amount is 1000LD
50Outward, all the same experiments such as animal grouping, medication, but remove the normal control group.Put to death mice in 48 hours behind the infective virus, dissect and get lung, win left side middle period lung and fix conventional dehydration, embedding, making paraffin section.Dye with indirect immunofluorescence, it is former to do spike with fluorescein-labeled resisiting influenza virus serum, by the indirect immunofluorescence combination, observe the virus antigen of infected mice lung internal specific, judge the effect of medicine to virus multiplication, the fluorescence number positive is many, shows that virion propagation is many, and compares between the work group.
Table 13: medicine of the present invention is to the influence of proliferation of influenza virus amount in the mouse lung
| Group | Dosage g/kg/d | Check total | Number positive | Positive rate (%) | Suppression ratio (%) |
| Virus control papova azoles group Folium Eriobotryae groups of grains Periostracum Cicadae granule (greatly) Periostracum Cicadae granule (in) Periostracum Cicadae granule (little) | - 0.07 2.75 11 5.5 2.75 | 197 198 199 199 203 225 | 106 95 92 99 107 106 | 54.01±4.64 48.00±4.02 47.20±4.03 47.73±4.20 49.80±3.91 52.70±3.54 | 0 11.13** 12.6** 11.63** 7.8 2.43 |
Compare with the virus control group:
*P＜0.01
The result shows: the proliferation of influenza virus amount obviously is less than the virus control group in the lung of the heavy dose of group of Periostracum Cicadae granule, with the virus control group significant difference (P＜0.01) is arranged relatively.Illustrate Periostracum Cicadae when 11g/kg/d dosage to mouse lung in influenza
The virus multiplication amount has significant inhibitory effect.
Brief summary: behind the influenza infection mice lungs, can cause that the inflammatory of lung tissue changes the formation viral pneumonia.Owing to lung tissue hyperemia, oozes out lungs weight is increased, and the increase of lung weight becomes positive correlation with its degree of inflammation.Often adopt lung index (lung weight/body weight) to represent the degree of lungs inflammation weight in test chamber, the lung index is big more to show that the inflammatory disorders of lung is heavy more, and vice versa.In addition, influenza virus is when causing that the lungs inflammation changes, be everlasting and breed in the lung, adopt the specific immunity fluorescent antibody to carry out the degree that labelling can reflect virus multiplication at laboratory, the high more expression virus multiplication of the ratio of specific fluorescence labelling amount is big more, therefore, often as another common counter of judging the medicine antivirus action.This experimental observation the influence of medicine of the present invention to proliferation of influenza virus amount in mice influenza virus property pneumonia and the lung, the result shows: when 11g/kg/d, 5.5g/kg/d dosage the mice influenzal pneumonia is had obvious inhibitory action; When 11g/kg/d dosage to mouse lung in proliferation of influenza virus obvious inhibitory action is arranged.
Experiment 9: medicine of the present invention is to the influence of the high air flue reaction of rat
Animal: the SD rat, male, body weight 160～180g is provided by Henan Province's Experimental Animal Center.The quality certification number: the moving word 01006 of doctor.
Medicine:
Medicine of the present invention: the same.
Asmeton capsule: Japanese Sankyo Co., Ltd produces, lot number MN531; Import drugs card number: 20000006; Date of manufacture: July calendar year 2001; Every capsules composition: methoxyphenamine hydrochloride 12.5mg, narcotine 7mg, aminophylline 25mg, chlorphenamine maleate 2mg, 46.5mg/ grain altogether; Indication: asthma, allergic cough; Adult's consumption: 2/time, 3 times/day.Be one of treatment asthma commonly used clinically and medicine of allergic cough, this medicine is as the Western medicine positive control drug.
Magical Folium Eriobotryae cough-stopping granule: the same.
Instrument: nebulizer: the YC-Y800 type, medical excusing from death nebulizer, the Yadu Science and Technology Co., Ltd., Beijing produces.Pclab bio signal acquisition system: this reaches the production of development in science and technology Co., Ltd the little letter in Beijing.Pressure transducer: MPX5050DP Motorola, the U.S. produces.γ-calculating instrument: SN-695 ria-determination instrument, last marine products.
Reagent:
1, egg protein: Huamei Bio-Engrg Co., provides, lot number: 0111.
2, interleukin 4 (IL-4) is put and is exempted from medicine box, and East Asia, Beijing immunological technique institute provides lot number: 20020628.
3, interleukin-6 (IL-6) is put and is exempted from medicine box, and East Asia, Beijing immunological technique institute provides lot number: 20020628.
4, interleukin 8 (IL-8) is put and is exempted from medicine box, and East Asia, Beijing immunological technique institute provides lot number: 20020628.
5, Bai Shuansu B2 (TXB2) is put and is exempted from medicine box, and East Asia, Beijing immunological technique institute provides lot number: 20020628.
6, Endothelin (ET-1) is put and is exempted from medicine box, and Beijing China English biotechnology research provides lot number: 20020630.
7, granulocyte-macrophage colony stimutaing factor (GM-CSF) is put and is exempted from medicine box, and Beijing China English biotechnology research provides lot number: 20020630.
Method:
Rat is put into the 4L glass bell jar respectively, imported 1 minute with the atomizing of the egg protein of 1mg/ml, occurring the cough animal in 1 minute is qualified responsive animal, selects qualified rat and is divided into following each group at random: 1, blank group.2, model group.3, Asmeton treatment group: 7mg/kg.4, Folium Eriobotryae cough-relieving treatment group: 0.23g/kg.5, Periostracum Cicadae treatment group heavy dose: 4g/kg.6, dosage: 2g/kg in the Periostracum Cicadae treatment group.7, Periostracum Cicadae treatment group low dose: 1g/kg.8, Asmeton prevention group: 7mg/kg.9, Folium Eriobotryae cough-relieving prevention group: 0.23g/kg.10, Periostracum Cicadae prevention group heavy dose: 4g/kg.11, dosage: 2g/kg in the Periostracum Cicadae prevention group.12, Periostracum Cicadae prevention group low dose: 1g/kg.
Aluminium hydroxide dry powder is dissolved in distilled water with 10% ratio, and heated and boiled 10 minutes does not stop to stir, and makes aluminum hydroxide sol liquid, filters, and gets supernatant, as adjuvant, dissolves in egg protein with this, joins the egg protein solution of 1mg/ml.Each treated animal (except that the blank group) is made subcutaneous liquid with freshly prepared 1% egg protein solution and is penetrated, every Mus is got 10 points altogether in the two metapedes sole of the foots, two groin, waist both sides, back of the body both sides, neck both sides, every some subcutaneous injection 0.05ml, while lumbar injection 0.5ml, amount to 1ml, the blank group is only injected aluminum hydroxide adjuvant, repeats once after 1 week again, makes rat sensitization.
The rat of respectively organizing of prevention administration begins to irritate the different medicine of stomach in injecting egg protein for the first time, and the rat of respectively organizing of treatment administration begins administration in injecting egg protein for the second time after one week, and blank group and model group are only irritated stomach deionized water 2ml/100g.
Each treated animal all begins high air flue reaction and excites processing in for the second time injecting egg protein after one week, rat is placed in the glass bell jar of 4L, connect ultrasound atomizer, atomizing sucks egg protein (normal control group with normal saline for the it) 15min of 0.4mg/ml, the mist amount is controlled at 1ml/2min, to excite asthma.In 2 weeks of continuous agitation, simultaneously each group gives different pharmaceutical, and device is surveyed cough with asthma incubation period under the animal waking state, cough with asthma number of times, respiratory frequency etc. below after two weeks animal being placed.
Next day is Animal Anesthesia, abdominal aortic blood; Get right lung, with 10ml normal saline lavation 3 times, reclaim bronchoalveolar lavage fluid, do following detection: the bronchoalveolar lavage fluid numeration of leukocyte, then 1500 rev/mins centrifugal 15 minutes, supernatant is surveyed IL-8, IL-6, IL-4, TXB2, ET-1, GM-CSF etc., and blood is also surveyed IL-4, IL-6, IL-8, TXB2, ET-1, GM-CSF etc.
Table 14 medicine of the present invention is to the influence of the high air flue reaction of rat
| Group | Dosage | Respiratory frequency increases percentage ratio | Amplitude of respiration increases percentage ratio |
| Dosage prevention group Periostracum Cicadae low dosage prevention group in the dosage treatment group Periostracum Cicadae low dose therapy group Asmeton prevention group Folium Eriobotryae cough-relieving prevention group Periostracum Cicadae high dose prevention group Periostracum Cicadae in the blank group model group Asmeton treatment group Folium Eriobotryae cough-relieving treatment group Periostracum Cicadae high-dose therapy group Periostracum Cicadae | 7mg/kg/d 0.23g/kg/d 4g/kg/d 2g/kg/d 1g/kg/d 7mg/kg/d 0.23g/kg/d 4g/kg/d 2g/kg/d 1g/kg/d | 4.70±0.92 ** 38.98±7.41 7.49±2.19 ** 11.15±2.1 8** 7.30±1.46 ** 10.76±1.99 ** 12.52±2.34 ** 6.01±1.70 ** 11.50±2.10 ** 7.92±1.49 ** 11.86±2.31 ** 13.66±2.59 ** | 8.28±1.43 ** 69.14±13.86 23.18±4.58 ** 35.92±6.54 ** 25.14±4.94 ** 36.13±6.93 ** 42.04±7.68 ** 23.24±4.51 ** 30.56±5.42 ** 25.30±4.28 ** 29.48±5.62 ** 33.92±6.32 ** |
Annotate: compare with model group
*P＜0.01
Table 15 medicine of the present invention is to high air flue reaction rat cough with asthma number of times, the preclinical influence of cough with asthma
| Group | Dosage | The cough with asthma number of times | Cough with asthma incubation period (s) |
| Dosage prevention group Periostracum Cicadae low dosage prevention group in the dosage treatment group Periostracum Cicadae low dose therapy group Asmeton prevention group Folium Eriobotryae cough-relieving prevention group Periostracum Cicadae high dose prevention group Periostracum Cicadae in the blank group model group Asmeton treatment group Folium Eriobotryae cough-relieving treatment group Periostracum Cicadae high-dose therapy group Periostracum Cicadae | 7mg/kg/d 0.23g/kg/d 4g/kg/d 2g/kg/d 1g/kg/d 7mg/kg/d 0.23g/kg/d 4g/kg/d 2g/kg/d 1g/kg/d | 1.70±0.64 ** 25.90±5.34 7.30±1.49 ** 9.50±2.17 ** 8.50±1.72 ** 12.90±1.79 ** 15.20±3.26 ** 5.70±1.42 ** 8.20±1.55 ** 8.30±1.34 ** 10.60±1.51 ** 13.10±2.42 ** | 190.12±37.02 ** 18.26±3.53 113.02±20.17 ** 77.07±15.76 ** 84.67±16.48 ** 76.67±13.71 ** 50.36±9.72 ** 137.27±25.73 ** 86.63±16.31 ** 86.42±17.35 ** 81.45±15.86 ** 50.33±10.15 ** |
Annotate: compare with model group
*P＜0.01
Table 16 medicine of the present invention is to the influence of relevant cell factor in the high air flue reaction rat bronchoalveolar lavage fluid
| Group | The example number | IL-6 | IL-8 | GMCSF | Leukocyte | ET-1 | IL-4 | TXB 2 |
| The low dose of treatment group of the low dose of prevention group of dosage treatment group Periostracum Cicadae Periostracum Cicadae in the dosage prevention group Periostracum Cicadae is organized in the heavy dose of treatment group of the heavy dose of prevention group of the two medicine treatment group Chinese patent medicine prevention group Chinese patent drugs for treatment group Periostracum Cicadaes Periostracum Cicadae Periostracum Cicadae in the two medicine preventions of blank group model group | 10 10 10 10 10 10 10 10 10 10 10 10 | 66.3±11.08 127.8±22.45 73.9±13.60** 75.0±15.95** 101.2±9.00 106.8±18.92 81.0±7.80** 82.4±10.17** 90.3±7.72* 98.8±12.64 95.6±10.11 101.0±8.08 | 0.58±0.08 1.33±0.27 0.69±0.22** 0.80±0.29* 1.03±0.19 1.08±0.19 0.84±0.18* 0.89±0.17* 0.98±0.13 1.01±0.12 0.99±0.13 1.03±0.14 | 1.35±0.26 3.73±0.64 1.55±0.39** 1.57±0.30** 2.73±0.62 2.82±0.66 1.67±0.48** 1.77±0.51** 1.78±0.45** 1.78±0.44** 1.86±0.44** 2.00±0.26** | 3.45±0.77 5.65±0.70 3.58±0.69** 3.61±0.61** 4.35±0.60* 4.40±0.42* 3.79±0.31** 3.85±0.40** 3.90±0.33** 4.02±0.77** 3.94±0.43** 4.06±0.12** | 1126.6±147.57 1501.7±92.89 1202.7±121.28** 1220.7±103.20** 1317.6±29.45** 1326.1±118.34 1215.6±145.14** 1255.0±85.14** 1251.5±108.99** 1253.3±74.86** 1289.6±95.50** 1315.8±82.13* | 17.61±0.65 50.46±2.79 19.73±0.99** 20.79±1.01** 29.64±3.97** 32.20±1.92** 23.13±1.91** 25.69±1.94** 31.33±2.34** 34.22±3.28** 37.05±1.69** 37.70±0.94** | 72.10±10.59 153.10±14.44 101.3±20.14** 107.20±25.54** 117.00±16.87** 121.7±14.11** 89.20±10.39** 90.30±11.65** 94.60±21.06** 95.20±15.14** 102.90±14.03** 103.30±19.91** |
Annotate: compare with model group,
*P＜0.05
*P＜0.01
Table 17 medicine of the present invention is to the influence of relevant cell because of giving in the high air flue reaction rat blood serum
| Group | The example number | IL-6 | IL-8 | GMCSF | ET-1 | IL-4 | TXB 2 |
| The low dose of treatment group of the low dose of prevention group of dosage treatment group Periostracum Cicadae Periostracum Cicadae in the dosage prevention group Periostracum Cicadae in the heavy dose of treatment group of the heavy dose of prevention group of the blank group model group Western medicine prevention group western medicine group Chinese patent medicine prevention group Chinese patent drugs for treatment group Periostracum Cicadae Periostracum Cicadae Periostracum Cicadae | 10 10 10 10 10 10 10 10 10 10 10 10 | 121.7±34.92 215.6±32.75 126.4±30.54** 134.5±25.95** 200.1±28.28 208.7±39.37 149.9±32.53* 152.7±27.56* 164.6±23.86 168.1±44.71 199.9±40.69 200.8±27.60 | 0.45±0.14 1.11±0.18 0.58±0.15** 0.63±0.18** 0.96±0.16 0.97±0.17 0.65±0.19** 0.71±0.22* 0.76±0.26 0.78±0.14* 0.77±0.15* 0.82±0.18 | 5.71±0.97 11.92±1.95 6.86±1.40** 7.13±1.61** 10.15±2.19 10.42±1.33 7.04±0.89** 7.37±1.41** 7.74±1.40** 7.89±1.60** 8.49±1.43* 8.58±1.67* | 273.3±34.39 266.0±66.84 230.0±63.76 238.2±50.38 256.2±47.77 251.3±31.56 251.1±42.25 254.0±45.56 260.2±34.65 268.8±37.58 283.6±36.75 287.9±26.71 | 17.73±0.84 52.7±2.12 20.1±1.09** 21.1±1.26** 30.3±4.21** 32.5±2.31** 23.4±2.24** 25.9±2.00** 31.9±2.62** 34.8±3.70** 37.7±2.21** 38.2±1.24** | 138.9±12.21 295.3±28.34 188.6±38.78** 189.9±27.45** 225.5±21.11** 227.0±32.02** 174.6±19.63** 176.6±19.12** 187.2±38.46** 190.3±30.18** 205.3±26.20** 206.6±36.9** |
Annotate: compare with model group,
*P＜0.05
*P＜0.01
The result: medicine of the present invention is high air flue reaction rat after to zygote protein excitation, its cough with asthma number of times be can suppress, respiratory frequency and amplitude of respiration reduced, prolong asthma incubation period, blood in the bronchoalveolar lavage fluid is counted accurately and inflammatory cytokine has inhibitory action, inflammatory cytokine in the blood also there is the obvious suppression effect, but ET-1 is not had obvious effect.
Conclusion: medicine of the present invention has the obvious suppression effect to the high anaphylaxis (cough with asthma and pneumonia) of high air flue reaction model rat.
Two, acute toxicity testing
Medicine acute toxicity test of the present invention
Experiment material:
1, be subjected to the reagent thing: medicine of the present invention (hereinafter to be referred as Periostracum Cicadae), produce by the special pharmaceutical factory of Henan Province's Olympic.Specification: 9 bags/box, 10 gram/bags.Clinical consumption: every day 3 times, each 1 bag.Every gram finished product is equivalent to crude drug in whole 2.30g approximately.Use concentration for improving, experiment is made into 73.3% concentration with extract powder (every gram contains crude drug 4.18 grams) with aquae destillata.Extract powder provides lot number, 010912 by the special pharmaceutical factory of Henan Province's Olympic.
2, laboratory animal: 20 of Kunming mouses, male and female half and half, body weight 18～20g is provided by Henan Province's Experimental Animal Center, the quality certification number: the moving word 01006 of doctor.
Method and result:
1 method: Kunming mouse use in experiment, after the fasting 12 hours (freely drink water), and gastric infusion, the filling stomach is three times in one day, 0.4ml/10g body weight at every turn, interval 5 hours.Observe every day such as animal hair, activity, the mental status, appetite, amount of drinking water and animal dead situation etc., observed continuously 7 days.
2 results: after the mouse stomach administration, in 7 days animal hair, activity, the mental status, appetite and Excreta etc. there is no unusual, no animal dead, body weight gain sees Table 18.The maximum dosage-feeding that records mice accumulative total medicine filling of the present invention on the one stomach is 367.7g crude drug/kg body weight, is equivalent to 319.7 times of clinical application amount.
Conclusion: medicine of the present invention can be irritated stomach volume gastric infusion with tolerant Cmax of mice and maximum, observes 7 days, does not find obvious acute toxic reaction, no animal dead.The maximum dosage-feeding that records medicine mouse stomach of the present invention administration is 367.7g crude drug/kg body weight (is equivalent to clinical consumption 319.7 times).
Table 18: medicine acute toxicity testing body weight change table of the present invention
| Male | Female | |
| The 7th day body weight after the body weight administration before the administration | 19.8*1.2 25.2±1.9 | 19.3±1.2 24.1±1.6 |
Three, long term toxicity test
Medicine of the present invention was given the continuous gastric infusion of rat 90 days and drug withdrawal 14 days with three dosage of 28.88g crude drug/kg body weight, 21.66g crude drug/kg body weight and 14.44g crude drug/kg body weight (be equivalent to respectively clinical application amount 80 times, 60 times and 40 times), observed issuable cumulative toxicity of rat and retardance toxic reaction.Experimental result shows: during the administration and after the drug withdrawal, three dosage treated animal body weight gains, routine blood test, blood biochemical mensuration, each main organs exponential sum histopathological examination there is no unusually, compare there was no significant difference with the blank group.Illustrate that medicine of the present invention does not have obvious cumulative toxicity and retardance toxic reaction to rat.
List of references:
1, Xu Shuyun chief editor. mice ammonia draws the method for coughing, pharmacological experimental method, second edition, 1992:1167, People's Health Publisher.
2, Xu Shuyun chief editor. the Cavia porcellus citric acid draws the method for coughing, pharmacological experimental method, second edition, 1992:1168 People's Health Publisher.
3, Xu Shuyun chief editor. the method for coughing is drawn in the cat electricity irritation, pharmacological experimental method, second edition, 1992:1167-1169, People's Health Publisher.
4, Xu Shuyun chief editor. isolated tracheal, lung bar laboratory method. pharmacological experimental method, second edition, 1992:1171-1173, People's Health Publisher.
5, Xu Shuyun chief editor. ear swelling method, pharmacological experimental method, second edition, 1992:719, People's Health Publisher.
6, Li Yikui chief editor. the hemolysin algoscopy. herbal pharmacology experimental methodology .1991:159-160, Shanghai science tech publishing house.
7, Yang Jun, Xu Jingya, Li Dongzhen etc. the anti inflammatory immunity pharmacological action of triptophenolide. Chinese herbal medicine 1995; 26 (1): 24-27.
8, Zhang Juntian chief editor. the experimental technique and the technology of antibiotic, antiviral drugs. modern pharmacology experimental technique .1999:1409-1470.
9, Wei Erqing, Zhang Weiping, Lu Zhiyong etc. clear-headed unconstrained Cavia porcellus measurement of bronchial responsiveness method. Chinese applied physiology magazine, 1997; 13 (1): 86-87.
10, Zhao Menghui, Zhang Lifen, Zhang Weiping, etc. the quantitative study of airway inflammation in the rat asthmatic model. Zhejiang Medical university journal, 1997; 26 (3): 100.
The specific embodiment
The invention will be further elaborated by the following examples.
Embodiment 1:
Prescription:
Periostracum Cicadae 414g, Radix Scutellariae 230g, Pheretima 276g, Bombyx Batryticatus 230g, Herba Schizonepetae 230g, Radix Asteris 276g, Radix Stemonae 414g, Fructus Chebulae 230g.
Preparation method:
A. get raw medicinal material by prescription, after wherein Herba Schizonepetae is soaked 2 hours, extracted volatile oil 3 hours, medicinal residues I and the residual liquid usefulness of purchasing in addition;
B. volatile oil adds 40 times of water gagings, and 4 times of amount beta-schardinger dextrin-s ground enclose 10 minutes with colloid mill, filters 70 ℃ of oven dry of clathrate, other usefulness of purchasing;
C. Periostracum Cicadae, Radix Scutellariae, Pheretima, Radix Asteris, the Radix Stemonae, Fructus Chebulae add 14720ml 70% alcohol reflux 3 times, and each 2 hours, filter, get medicinal residues II and filtrate, filtrate merges, and recovery ethanol is not to there being pure flavor, and it is standby to get medicinal liquid;
D. the medicinal residues I of medicinal residues II and step a and residual liquid merge, and add Bombyx Batryticatus, add water 18400ml, decoct 3 times, each 2.5 hours, merging filtrate filtered, and filtrate decompression is concentrated into 70 ℃ of relative densities and is about 1.3, merge with step c gained medicinal liquid, vacuum drying is ground into fine powder;
E. fine powder adds dextrin 450g mixing, with 80% ethanol system granule, and in the clathrate adding granule with step b gained, mixing, granule is made in packing.
Embodiment 2:
Prescription:
Periostracum Cicadae 400g, Radix Scutellariae 230g, Pheretima 250g, Bombyx Batryticatus 250g, Herba Schizonepetae 200g, Radix Asteris 270g, Radix Stemonae 430g, Fructus Chebulae 240g.
Preparation method:
A. get raw medicinal material by prescription, after wherein Herba Schizonepetae is soaked 2 hours, extracted volatile oil 2.5 hours, medicinal residues I and the residual liquid usefulness of purchasing in addition;
B. volatile oil adds 45 times of water gagings, and 5 times of amount beta-schardinger dextrin-s ground enclose 10 minutes with colloid mill, filters 68 ℃ of oven dry of clathrate, other usefulness of purchasing;
C. Periostracum Cicadae, Radix Scutellariae, Pheretima, Radix Asteris, the Radix Stemonae, Fructus Chebulae add the alcohol reflux 4 times of 14720ml 70%, each 1.5 hours, filter, medicinal residues II and filtrate, filtrate merges, and reclaims ethanol to there not being the alcohol flavor, medicinal liquid is standby;
D. the medicinal residues I of medicinal residues II and step a and residual liquid merge, and add Bombyx Batryticatus, add water 18400ml, decoct 3 times, each 2.5 hours, merging filtrate filtered, and filtrate decompression is concentrated into 70 ℃ of relative densities and is about 1.3, merge with step c gained medicinal liquid, vacuum drying is ground into fine powder;
E. fine powder adds dextrin 450g mixing, with 80% ethanol system granule, and in the clathrate adding granule with step b gained, mixing, granule is made in packing.
Embodiment 3:
Prescription:
Periostracum Cicadae 450g, Radix Scutellariae 230g, Pheretima 290g, Bombyx Batryticatus 240g, Herba Schizonepetae 230g, Radix Asteris 280g, Radix Stemonae 420g, Fructus Chebulae 220g.
Preparation method:
A. get raw medicinal material by prescription, after wherein Herba Schizonepetae is soaked 2 hours, extracted volatile oil 3 hours, medicinal residues I and the residual liquid usefulness of purchasing in addition;
B. Periostracum Cicadae, Radix Scutellariae, Pheretima, Radix Asteris, the Radix Stemonae, Fructus Chebulae add the alcohol reflux 3 times of 14720ml 70%, each 3 hours, filter, medicinal residues II and filtrate, filtrate merges, and reclaims ethanol to there not being the alcohol flavor, medicinal liquid A is standby;
D. the medicinal residues I of medicinal residues II and step a and residual liquid merge, and add Bombyx Batryticatus, add water 18400ml, decoct 2 times, and each 3 hours, merging filtrate filtered, and filtrate decompression is concentrated into 70 ℃ of relative densities and is about 1.2, merges with medicinal liquid A, gets medical liquid B;
E. volatile oil and medical liquid B merge, and add correctives, and mixing adds water and is settled to 10000ml, packing, and sterilization is made oral liquid, every 10ml.
Embodiment 4:
Prescription:
Periostracum Cicadae 420g, Radix Scutellariae 200g, Pheretima 260g, Bombyx Batryticatus 238g, Herba Schizonepetae 225g, Radix Asteris 276g, Radix Stemonae 427g, Fructus Chebulae 232g.
Preparation method:
A. get raw medicinal material by prescription, wherein Herba Schizonepetae adds suitable quantity of water and soaks after 2 hours, extracts volatile oil 4 hours, medicinal residues I and the residual liquid usefulness of purchasing in addition;
B. volatile oil adds 50 times of water gagings, and 5 times of amount beta-schardinger dextrin-s ground enclose 10 minutes with colloid mill, filters 75 ℃ of oven dry of clathrate, other usefulness of purchasing;
C. Periostracum Cicadae, Radix Scutellariae, Pheretima, Radix Asteris, the Radix Stemonae, Fructus Chebulae add the alcohol reflux 2 times of 14720ml 70%, each 3 hours, filter, medicinal residues II and filtrate, filtrate merges, and reclaims ethanol to there not being the alcohol flavor, medicinal liquid is standby;
D. the medicinal residues I of medicinal residues II and step a and residual liquid merge, and add Bombyx Batryticatus, add water 18400ml, decoct 2 times, each 3 hours, merging filtrate filtered, and filtrate decompression is concentrated into 70 ℃ of relative densities and is about 1.4, merge with step c gained medicinal liquid, vacuum drying is ground into fine powder;
E. fine powder adds starch 450g, adds the clathrate of step b gained again, mixing, and tabletting is made tablet.
Embodiment 5:
Prescription:
Periostracum Cicadae 436g, Radix Scutellariae 215g, Pheretima 273g, Bombyx Batryticatus 243g, Herba Schizonepetae 241g, Radix Asteris 260g, Radix Stemonae 435g, Fructus Chebulae 227g.
Preparation method:
A. get raw medicinal material by prescription, wherein Herba Schizonepetae adds suitable quantity of water and soaks after 3 hours, extracts volatile oil 2 hours, medicinal residues I and the residual liquid usefulness of purchasing in addition;
B. volatile oil adds 45 times of water gagings, and 4 times of amount beta-schardinger dextrin-s grind enclose with colloid mill, filters 70 ℃ of oven dry of clathrate, other usefulness of purchasing;
C. Periostracum Cicadae, Radix Scutellariae, Pheretima, Radix Asteris, the Radix Stemonae, Fructus Chebulae add the alcohol reflux 3 times of 14720ml 70%, each 2 hours, filter, medicinal residues II and filtrate, filtrate merges, and reclaims ethanol to there not being the alcohol flavor, medicinal liquid is standby;
D. the medicinal residues I of medicinal residues II and step a and residual liquid merge, and add Bombyx Batryticatus, add water 18400ml, decoct 2 times, each 3 hours, merging filtrate filtered, and filtrate decompression is concentrated into 70 ℃ of relative densities and is about 1.3, merge with step c gained medicinal liquid, vacuum drying is ground into fine powder;
E. fine powder adds dextrin 450g mixing, with 80% ethanol system granule, and in the clathrate adding granule with step b gained, mixing, the fill capsule is made capsule.
Claims (10)
1. Chinese medicine composition is characterized in that the prescription of this Chinese medicine composition contains following bulk drugs material:
Periostracum Cicadae 400-450 part, Radix Scutellariae 200-250 part, Pheretima 250-300 part, Bombyx Batryticatus 200-250 part, Herba Schizonepetae 200-250 part, Radix Asteris 250-300 part, Radix Stemonae 400-450 part, Fructus Chebulae 200-250 part.
2. Chinese medicine composition according to claim 1 is characterized in that the prescription of this Chinese medicine composition contains following bulk drugs material:
414 parts of Periostracum Cicadaes, 230 parts of Radix Scutellariaes, 276 parts of Pheretimas, 230 parts of Bombyx Batryticatus, 230 parts of Herba Schizonepetae, 276 parts of Radix Asteriss, 414 parts of the Radixs Stemonae, 230 parts of Fructus Chebulaes.
3. Chinese medicine composition according to claim 1 and 2, the dosage form that it is characterized in that this Chinese medicine composition is tablet, granule, capsule, pill, oral liquid, injection.
4. the preparation method of claim 1 or 2 described Chinese medicine compositions is characterized in that this method comprises the following steps:
A. get raw medicinal material by prescription, wherein Herba Schizonepetae adds suitable quantity of water and soaks after 1～3 hour, extracts volatile oil 2～4 hours, medicinal residues I and the residual liquid usefulness of purchasing in addition;
B. Periostracum Cicadae, Radix Scutellariae, Pheretima, Radix Asteris, the Radix Stemonae, Fructus Chebulae to add an amount of concentration be 60～80% alcohol reflux 2～4 times, each 1～3 hour, filter, medicinal residues II and filtrate, filtrate merges, and reclaims ethanol to there not being the alcohol flavor, medicinal liquid A is standby;
C. the medicinal residues I of medicinal residues II and step a and residual liquid merging adds Bombyx Batryticatus and suitable quantity of water, decocts 2～4 times, and each 2-3 hour, merging filtrate filtered, and filtrate decompression is concentrated into 70 ℃ of relative densities and is about 1.2～1.4, merges with medicinal liquid A, gets medical liquid B;
D. volatile oil and medical liquid B are merged, add liquid preparation adjuvant commonly used and make liquid preparation by the liquid preparation common process; Perhaps
Volatile oil is added 30～50 times of water gagings, and 3～5 times of amount beta-schardinger dextrin-s grind enclose with colloid mill, filter 65～75 ℃ of oven dry of clathrate; In addition medical liquid B is carried out drying, be ground into fine powder; Add the corresponding conventional adjuvant according to required solid preparation in fine powder, add clathrate, common process is made solid preparation.
5. according to the preparation method of the described Chinese medicine composition of claim 4, it is characterized in that steps d is: fine powder adds an amount of dextrin mixing, with 80% ethanol system granule, and in the clathrate adding granule with gained, mixing, granule is made in packing.
6. claim 1 or the 2 described Chinese medicine compositions application in the preparation cough suppressing medicine.
7. claim 1 or the 2 described Chinese medicine compositions application in the preparation antiviral drugs.
8. claim 1 or the 2 described Chinese medicine compositions application in the preparation suppressing panting calming medicine.
9. claim 1 or the 2 described Chinese medicine compositions application in the preparation antibacterial medicines.
10. claim 1 or the 2 described Chinese medicine compositions application in the preparation anti-inflammatory drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101911365A CN101181561B (en) | 2007-12-10 | 2007-12-10 | Chinese medicine as well as preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101911365A CN101181561B (en) | 2007-12-10 | 2007-12-10 | Chinese medicine as well as preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101181561A true CN101181561A (en) | 2008-05-21 |
| CN101181561B CN101181561B (en) | 2010-11-17 |
Family
ID=39447074
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007101911365A Active CN101181561B (en) | 2007-12-10 | 2007-12-10 | Chinese medicine as well as preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101181561B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016159581A3 (en) * | 2015-03-27 | 2016-12-01 | 한국 한의학 연구원 | Composition for innate immunity enhancement and antiviral activity containing aster tataricus extract as active ingredient |
| CN109022325A (en) * | 2018-08-28 | 2018-12-18 | 包平 | A kind of method of organotin in degradation water body |
| CN110946831A (en) * | 2019-12-19 | 2020-04-03 | 金陵药业股份有限公司 | Novel preparation process of traditional Chinese medicine composition |
| CN113058011A (en) * | 2019-12-26 | 2021-07-02 | 金陵药业股份有限公司 | Preparation method of traditional Chinese medicine composition for removing impurities by using ceramic membrane |
-
2007
- 2007-12-10 CN CN2007101911365A patent/CN101181561B/en active Active
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016159581A3 (en) * | 2015-03-27 | 2016-12-01 | 한국 한의학 연구원 | Composition for innate immunity enhancement and antiviral activity containing aster tataricus extract as active ingredient |
| CN109022325A (en) * | 2018-08-28 | 2018-12-18 | 包平 | A kind of method of organotin in degradation water body |
| CN110946831A (en) * | 2019-12-19 | 2020-04-03 | 金陵药业股份有限公司 | Novel preparation process of traditional Chinese medicine composition |
| CN110946831B (en) * | 2019-12-19 | 2022-03-01 | 金陵药业股份有限公司 | Novel preparation process of traditional Chinese medicine composition |
| CN113058011A (en) * | 2019-12-26 | 2021-07-02 | 金陵药业股份有限公司 | Preparation method of traditional Chinese medicine composition for removing impurities by using ceramic membrane |
| CN113058011B (en) * | 2019-12-26 | 2022-12-06 | 金陵药业股份有限公司 | Preparation method of traditional Chinese medicine composition for removing impurities by using ceramic membrane |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101181561B (en) | 2010-11-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102669466B (en) | 21-42-days-old meat duck feed and preparation method thereof | |
| CN103704513B (en) | Feed for treating swine plague and preparation method thereof | |
| CN104922586B (en) | A kind of preparation and its application of the probiotics fermention Chinese medicine preparation for preventing chicken coccidiasis | |
| CN103478508B (en) | Chinese medicinal composition and feed for improving chicken immunity and preparation method of composition and feed | |
| CN103749982A (en) | Feed for improving egg yield, traditional Chinese medicine additive and preparation method thereof | |
| CN110227141A (en) | It is a kind of for alleviating the fermented type Chinese materia medica preparation and preparation method of livestock and poultry Rheology due to caused by bacterium or virus | |
| CN104547521A (en) | Compound fermentation traditional Chinese medicine for enhancing immunity of livestock and poultry and preparation method of compound fermentation traditional Chinese medicine | |
| CN101181561B (en) | Chinese medicine as well as preparation method and application thereof | |
| CN103028001B (en) | It is a kind of be used for relieving asthma, the Chinese prescription of antibechic, anti-inflammatory, Its Preparation Method And Use | |
| CN102895326B (en) | Traditional Chinese medicine composition for treating infantile common cold and preparation method for traditional Chinese medicine composition | |
| CN102526568B (en) | Traditional Chinese medicine compound composition | |
| CN102058810B (en) | Lung-clearing asthma-relieving phlegm-reducing Chinese patent drug | |
| CN103494927A (en) | Traditional Chinese medicine composition for treating chicken respiratory disease and preparation method thereof | |
| CN104546967A (en) | Composite venenum bufonis injection and preparation method thereof | |
| CN101152379A (en) | Traditional Chinese medicine for treating cough and technique of preparing the same | |
| CN109432287B (en) | Traditional Chinese medicine oral liquid for preventing and treating excessive heat syndrome of poultry qi system and preparation method thereof | |
| CN103656320B (en) | For preventing and treating the oral administered compound Chinese medicine preparation of birds anemofrigid cold, influenza | |
| CN103417653B (en) | Veterinary-use compound pure Chinese herbal medicine for treating coccidium and preparation method of oral liquid of same | |
| CN104922530A (en) | Drug combination for preventing and treating chicken colibacillosis and preparing method thereof | |
| CN111249318A (en) | Hericium erinaceus culture medium for treating wind-heat type common cold, mulberry leaf and hericium erinaceus transformed mycelium, extract and application | |
| CN104288236A (en) | Veterinary Shuanghuanglian oral liquid preparation processed by using probiotics and preparation method thereof | |
| CN101085048B (en) | Traditional Chinese medicine for detoxicating for animals and preparation method thereof | |
| CN104397370A (en) | Chicken feed for increasing daily gain and preparation method thereof | |
| CN109452495A (en) | A kind of prevention and treatment Procambius clarkii spiral shell substance disease Chinese herbal feed additive and the preparation method and application thereof | |
| CN103082286A (en) | Health-care food for enhancing immunity and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |