CN104257697B - It is a kind of to prevent or the careless composition of silkworm for the treatment of breathing problem and its application - Google Patents
It is a kind of to prevent or the careless composition of silkworm for the treatment of breathing problem and its application Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/062—Ascomycota
- A61K36/066—Clavicipitaceae
- A61K36/068—Cordyceps
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
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Abstract
The invention belongs to the field of Chinese medicines, a kind of prevent or the careless composition of silkworm for the treatment of breathing problem and its application is disclosed.A kind of careless composition of the silkworm for preventing or treating breathing problem, mainly by 30~70 parts, 0.1~10 part of 10~50 parts of Cordyceps militaris and arginine.The prevention that is prepared by said composition or treating the Chinese patent drug of breathing problem, there is 5 outstanding lipoxidase enzyme inhibition activities, airway contraction inhibitory activity, airway inflammation inhibitory action, ear to swell anti-inflammatory effects, antibechic and expectorant activity, can effectively prevent or treat asthma, chronic obstructive pulmonary disease, acute/chronic bronchitis, allergic rhinitis, cough, abundant expectoration, acute lower respiratory infection disease (bronchitis and capillary bronchitis), pharyngitis, tonsillitis, the respiratory illness such as the acute upper respiratory infection disease such as laryngitis.
Description
Technical field
The invention belongs to the field of Chinese medicines, it is related to a kind of careless composition of the silkworm for preventing or treating breathing problem and its answers
With.
Background technology
Respiratory disease is a kind of common disease and frequently-occurring disease, and major lesions are in trachea-bronchial epithelial cell, lung and thoracic cavity, disease
Become cough more than the lighter, pectoralgia, breathing to be obstructed, severe one expiratory dyspnea, cause anoxic or even respiratory failure and lethal.Because air is dirty
Dye, smoking, aging population and other factors, make chronic obstructive pulmonary disease both domestic and external, bronchial astehma, lung cancer, lung more
The incidence of disease of the disease such as property interstitial fibrosis and pulmonary infection is dissipated, the death rate is growing on and on.
Cordyceps sinensis [Cordyceps sinensis (Berk.) Sacc.] be in the medical treasure-house of China with wild ginseng, deer
Fine and soft full name is precious for one in " three is big precious ", stands high in reputation, it can be obviously promoted body immunity, to human body maincenter god
There is significant curative effect through system, cardiovascular system, respiratory system, many physiological functions of digestive system.Wherein in respiratory system table
It is now：Lung kidney-nourishing, hemostasis and phlegm can be protected, it will be apparent that diastole bronchial smooth muscle, a series of effects of enhancing adrenal gland etc. thus it is right
Mitigation symptom effect can be played by improving the diseases such as PFT, senile chronic bronchitis, asthma, pulmonary emphysema, pulmonary heart disease.But winter worm
Summer grass can not still realize artificial growth at present due to growth particularity, expensive, it is impossible to clinically extensive use.Pupa worm
Careless [Cordyc epsmilitaris (Fr.) Link] also known as northern Chinese caterpillar Fungus, pupa grass, belong to Ascomycetes, Hypocreales, wheat
Angle Cordycepps, Cordyceps sinensis fungus, are the type sepecies of Cordyceps.Cordceps militaris, also referred to as silkworm grass are cultivated by host of silkworm larva,
Its cordyceps sinensis form is closer to natural cses.《Xinhua's Compendium of Materia Medica》Claim its " sweet, mild-natured ", with " beneficial lung kidney, mend marrow, only
Effect of blood resolving sputum ".Modern study shows that Cordceps militaris has enhancing body immunity and antineoplastic action, is coughed in the treatment deficiency syndrome of the lung
Cough, in terms of bronchitis, asthma and antibacterial, antithrombotic, it is anti-oxidant in terms of also there is remarkable effect.But, respiratory tract disease
Disease is related to various leucocytes, cell factor and inflammatory mediator, therefore the Cordyceps militaris of artificial cultivation and silkworm grass are only with single raw material
The extensive prevention and therapeutic action of respiratory system difficult to realize.
In order to overcome the limitation of existing medicine, it is necessary to which the cause of disease can fundamentally be treated and effectively improve disease by developing
The new drug of symptom.
The content of the invention
The purpose of the present invention be for prior art defect there is provided it is a kind of prevent or treatment breathing problem silkworm grass
Composition and its application.
Prevent or the careless composition of silkworm for the treatment of breathing problem and its preparation it is a further object of the present invention to provide a kind of
Method.
The purpose of the present invention can be achieved through the following technical solutions：
It is a kind of prevent or treatment breathing problem the careless composition of silkworm, mainly by 30~70 parts of silkworm grass, Cordyceps militaris 10
~50 parts and 0.1~10 part of arginine composition, are preferably by 50~70 parts of silkworm grass, 30~50 parts of Cordyceps militaris and arginine 0.1
~5 parts of compositions.
Application of the careless composition of the described silkworm of prevention or treatment breathing problem in breathing problem medicine is prepared.
Described symptoms of respiratory disease be asthma, chronic obstructive pulmonary disease, acute/chronic bronchitis, allergic rhinitis,
On cough, abundant expectoration, acute lower respiratory infection disease (bronchitis and capillary bronchitis), pharyngitis, tonsillitis, laryngitis etc. are acute
Respiratory tract infection disease etc..
A kind of preparation method of the careless composition of the silkworm for preventing or treating breathing problem, comprises the following steps：
A. silkworm grass, Cordyceps militaris, three kinds of raw materials of arginine are first separately dried crushing, mesh number is no less than 20 mesh；
B. Chinese medicine composition of the present invention is uniformly obtained after the powder raw material after crushing is weighed by weight percentage；Wherein institute
The percentage by weight for the raw material stated is constituted：0.1~10 part of 30~70 parts of silkworm grass, 10~50 parts of Cordyceps militaris and arginine, it is excellent
Elect 0.1~5 part of 50~70 parts of silkworm grass, 30~50 parts of Cordyceps militaris and arginine as.
Wherein, the mesh number that the silkworm grass, Cordyceps militaris, three kinds of raw materials of arginine are crushed is 20-80 mesh.
The careless composition of the silkworm of prevention or treatment breathing problem prepared according to the method described above.
Described prevention or the Chinese medicine composition for the treatment of breathing problem is preparing prevention or treatment breathing problem medicine
In application, the preferred asthma of described symptoms of respiratory disease, chronic obstructive pulmonary disease, acute/chronic bronchitis, allergia nose
Inflammation, cough, abundant expectoration, acute lower respiratory infection disease (bronchitis and capillary bronchitis), pharyngitis, tonsillitis, laryngitis etc. are anxious
Property upper respiratory tract infection etc..
Said composition particularly can prepared prevention or controlled in the application in preparing prevention or treatment breathing problem medicine
Treat asthma, chronic obstructive pulmonary disease, acute/chronic bronchitis, allergic rhinitis, cough, abundant expectoration, acute lower respiratory infection disease
Applied in the acute upper respiratory infection disease such as (bronchitis and capillary bronchitis), pharyngitis, tonsillitis, laryngitis.The present invention is living
Property used better than the single of each raw material, and better than cordyceps sinensis, new paragon is provided for the prevention and treatment of breathing problem.
Embodiment
The present invention is further elaborated below with reference to specific embodiment, these examples are for illustration purposes only, without
For limiting the scope of the invention.The experimental animal of the present invention, purchased from Academy of Military Medicine, PLA experimental animal
Center (production licence number：SCXK (army) 2007-004).
Embodiment 1
500 kilograms of Cordyceps militaris, 300 kilograms of silkworm grass, 5 kilograms of arginine are taken, size-reduced machine is crushed and obtains theirs respectively
Powder, mesh number is controlled in 80 mesh.Above-mentioned powdery Cordyceps militaris, silkworm grass and arginine are mixed, stirred, finally will
The mixture handles the Chinese patent drug for obtaining tablet, capsule, granule, electuary or powder through preparation processing.
Embodiment 2
Double centner Cordyceps militaris, 700 kilograms of silkworm grass, 5 kilograms of arginine are taken, size-reduced machine is crushed and obtains theirs respectively
Powder, mesh number is controlled in 20 mesh.Above-mentioned powdery Cordyceps militaris, silkworm grass and arginine are mixed, stirred, finally will
The mixture handles the Chinese patent drug for obtaining tablet, capsule, granule, electuary or powder through preparation processing.
The different formulations of embodiment 3 are to relieving cough and reducing sputum active influence
Sample preparation：Sample 1：This product (is prepared) by the method for embodiment 1；Sample 2：Silkworm grass；Sample 3：Cordyceps militaris；Sample
Product 4：Cordyceps sinensis；
Animal experiment method：
Ammoniacal liquor is drawn and coughs the influence of mouse and uses ammonia induced cough in mice, preliminary experiment ammoniacal liquor draws method of coughing and screens a collection of constitution
Measure the mouse not coughed in 18~22g kunming mice, 3min to refuse to select, after after the stable 2d of mouse, take qualified mouse
60, male and female half and half are randomly divided into 6 groups, control group (physiological saline), NIANCIAN MILIAN CHUANBEI PIPA GAO group by weight
(10g/kg), each sample group (0.6g crude drugs/kgbw), successive administration 7d, each gavage 0.2mL/10g solution of mouse, last
Water 12h is can't help in fasting before administration, in after last dose 1h, mouse is placed in self-control closed glass container, ultrasonic atomizer spray
Enter after ammoniacal liquor 20s, mouse, record mouse cough latent time and the interior cough number of times of 3min are taken out immediately.As a result such as table 1 is visible,
Product prepared by the present invention plays the role of extension mouse cough incubation period and reduces mouse cough number of times, is compared with model control group
There were significant differences, and this effect is better than NIANCIAN MILIAN CHUANBEI PIPA GAO, sample 2 (silkworm grass), sample 3 (Cordyceps militaris), sample 4
(cordyceps sinensis).
Table 1 to ammonia induced cough in mice cough number of times and cough latent period influence (N=10)
| Group | Dosage | Cough latent period/s | Cough number of times in 3min |
| Control group | --- | 18.98±4.45 | 28.68±6.56 |
| NIANCIAN MILIAN CHUANBEI PIPA GAO group | 10g/kg | 50.36±11.53** | 13.52±4.05** |
| Sample 1 | 0.6g/kg | 51.10±11.05** | 11.40±2.36** |
| Sample 2 | 0.6g/kg | 36.58±9.35** | 14.56±2.63** |
| Sample 3 | 0.6g/kg | 33.60±8.94* | 17.87±5.19* |
| Sample 4 | 0.6g/kg | 37.05±10.30* | 13.04±2.18** |
Note：Compared with control group, * P ＜ 0.05, * * P ＜ 0.01
Draw the influence preliminary experiment for coughing cavy to citric acid, cavy is put into self-control closed glass container, treats it in container
After interior stable 1min, at the uniform velocity 17.5g/L citric acid is sprayed into container with ultrasonic atomizing inhaler, spray time is 40s,
It is defined by the cough that the first fullness of tone occurs in cavy, start recording guinea pig cough's incubation period and the interior cough number of times of 5min, cough
Number of times ＜ 10 times and 30 persons of ＞ refuse to select.
Next day, which will be selected, screens random point 6 groups of qualified cavy 42, every group 7, be divided into each sample group (0.4g crude drugs/
Kgbw), control group (physiological saline), NIANCIAN MILIAN CHUANBEI PIPA GAO group (6.1g/kg), each group gastric infusion, control group
Physiological saline is given, 1 time a day, continuous 7d can't help 1h after water 12h, last dose in fasting before last dose and press preliminary experiment side
Method repeats to draw to cough experiment, records guinea pig cough's number of times in guinea pig cough's incubation period and 5min.As a result such as table 2 is visible, present invention system
Standby product plays the role of prolonged guinea pig cough latent period and reduces guinea pig cough's number of times, and being compared with model control group has significance difference
Different, this effect is better than NIANCIAN MILIAN CHUANBEI PIPA GAO, sample 2 (silkworm grass), sample 3 (Cordyceps militaris), (the worm summer in winter of sample 4
Grass).
Table 2 cavy citric acid is drawn the method for coughing cough number of times investigate (N=7)
| Group | Dosage | Cough latent period/s | The interior cough number of times of 5min/time |
| Control group | --- | 20.35±3.24 | 26.29±6.32 |
| NIANCIAN MILIAN CHUANBEI PIPA GAO group | 6.1g/kg | 69.52±8.33** | 14.05±4.08** |
| Sample 1 | 0.4g/kg | 79.44±5.29** | 13.28±4.31** |
| Sample 2 | 0.4g/kg | 67.60±5.19** | 18.42±3.61** |
| Sample 3 | 0.4g/kg | 57.79±4.83** | 19.46±1.76** |
| Sample 4 | 0.4g/kg | 65.29±5.42** | 14.51±3.76** |
Note：Compared with control group, * P ＜ 0.05, * * P ＜ 0.01
Influence to mouse PSP takes Kunming mouse 60, male and female half and half, be divided into each sample group (0.6g crude drugs/
Kgbw), control group (physiological saline), NIANCIAN MILIAN CHUANBEI PIPA GAO group (10g/kg), every group 10, each group presses above-mentioned dose
Gastric infusion is measured, 1 time a day, continuous 7d, the model group then isometric physiological saline 0.1mL/10g of gavage, before last dose, fasting
It can't help after water 12h, last dose 30min, give the phenol red solution of mouse peritoneal injection 0.5%, dosage is every 0.5mL, injection
The neck that breaks after 1h puts to death mouse, cuts one section of tracheae along thyroid cartilage, the tracheae requirement that every mouse is cut is isometric, is put into centrifuge tube
In, 3mL physiological saline and 1mol/L sodium hydroxide solution 0.2mL are added, centrifuges (rotating speed 2000r/min, time 5min), takes
Supernatant, measures at ultraviolet-uisible spectrophotometer 546nm wavelength and records light absorption value.As a result as seen in Table 3, present invention system
Standby product can dramatically increase mouse tracheae phenols contents, be compared that there were significant differences with model control group, and this effect is better than
NIANCIAN MILIAN CHUANBEI PIPA GAO, sample 2 (silkworm grass), sample 3 (Cordyceps militaris), sample 4 (cordyceps sinensis).
Table 3 to mouse PSP influence (N=10)
| Group | Dosage | Phenol red/(μ gmL-1) |
| Control group | --- | 0.35+0.08 |
| NIANCIAN MILIAN CHUANBEI PIPA GAO group | 6.1g/kg | 0.50+0.11** |
| Sample 1 | 0.6g/kg | 0.54+0.08** |
| Sample 2 | 0.6g/kg | 0.41+0.06* |
| Sample 3 | 0.6g/kg | 0.40+0.05* |
| Sample 4 | 0.6g/kg | 0.47+0.08** |
Note：Compared with control group, * P ＜ 0.05, * * P ＜ 0.01
Product prepared by the comprehensive visible present invention has stronger relieving cough and reducing sputum effect, and it is acted on better than the kind Buddhist nunnery honey refining river of thought
Shellfish loquat leaf extract, sample 2 (silkworm grass), sample 3 (Cordyceps militaris), sample 4 (cordyceps sinensis).
The present invention of embodiment 4 is to 5- lipoxidase enzyme inhibitions
Use rat basophilic granulocytic leukemia cell (Rat basophilic leukemia cell, PBL-1), profit
With the RPMI culture mediums without serum, after being stabilized under the conditions of 37 DEG C, sample 1 (being prepared by the method for embodiment 1) is added respectively
(prepared with sample 2 by the method for embodiment 2), arachidonic acid (arachidonic acid), generation white three are added as matrix
Alkene 15 minutes.The leukotriene amount of generation utilizes cysteinyl leukotriene EIA instruments (cysteinyl leukotriene EIA
Kit) detected.Medicine has used 5- lipoxidase inhibitors Zileuton (zileuton) and montelukast as a comparison
(montelukast).From table 4, the composition (sample 1 and sample 2) prepared by the present invention has the fatty oxygen of outstanding 5-
Synthase inhibition.
Table 4 to 5- lipoxidase enzyme inhibition rates influence (N=18)
The present invention of embodiment 5 is to bronchoconstriction inhibitory action
To cavy intravenous injection 2ml/kg antiovalbumins antiserum (anti-ovalbumin antiserum), sensitization.
After sensitization 48 hours, put to death, win bronchus.It is desk-top it is bright in, removal stick in after its hetero-organization on bronchus, with containing 2-
The mode of 3 cartilages, carries out circular incision.After incision in the state of bronchial musculature is retained, the cartilaginous part of ring is cut
Point, after the connecting line of both sides, it is allowed to be suspended in PBS liquid, after stable certain time, is put into 10 μ g/ml carbachols, causes maximum limit
The contraction of degree.5 μm of ol Indomethacins of addition after bronchus, stabilization are also washed with desk-top afterwards, is added after 1 minute and adds sample respectively
Product 1 (being prepared by the method for embodiment 1) and sample 2 (being prepared by the method for embodiment 2), add 20 μ g/ml ovalbumins after 5 minutes,
Induce and shrink, calculate bronchoconstriction inhibiting rate (%).Using sharp Pulan (rolipram) be used as comparison medicine.From table 5,
The composition (sample 1 and sample 2) prepared by the present invention has significant bronchoconstriction inhibitory activity.
Table 5 to bronchoconstriction inhibiting rate influence (N=10)
The present invention of embodiment 6 is to bronchitis inhibitory action
The μ g ovalbumins of female mice 10 and aluminium hydroxide 1 is injected intraperitoneally：1 mixed liquor 0.2ml is sensitized, administration time
Respectively the 0th, 7 and 14 days.After sensitization 8 days and 10 days, 1.0% egg protein is fabricated to aerosol using high pressure air
Agent, sprays 50 minutes, induces airway inflammation.It is every in the morning, afternoon respectively untill playing 23 days after 21 days after initial sensitization
It is twice orally to control drug and sample 1 (being prepared by the method for embodiment 1) and sample 2 (being prepared by the method for embodiment 2).Finally
After inflammation induction 24 hours, using 1.5ml phosphate buffer solutions (pH7.2), wash after bronchovesicular, collect bronchus
Alveolar cleaning solution, the leukocyte cell quantity in cleaning solution is detected with blood analyser.With negative control group (physiological saline)
Leukocyte cell number is defined, and calculates pulmonary branches bronchitis inhibiting rate (%).Using sharp Pulan (rolipram) be used as comparison medicine.
From table 6, the composition (sample 1 and sample 2) prepared by the present invention has significant bronchitis inhibitory activity.
Table 6 to bronchitis inhibiting rate influence (N=10)
Anti-inflammatory inhibitory action of the present invention of embodiment 7 to ear swelling
Male mice distinguishes orally administration control drug and sample 1 (being prepared by the method for embodiment 1) and sample 2 (by implementation
It is prepared by the method for example 2), after 1 hour, in the right ear inner side and outer side of mouse, uniformly smear with 3% crotons of acetone solution
Oil, induces ear swelling.After swelling induces 4 hours, after the lethal mouse of etherization, pass through THICKNESS CALCULATION ear thickness.With
The swelling degree of negative control group (physiological saline) is defined, and calculates inhibiting rate (%).Using celecoxib (Celecoxib) conduct
Comparison medicine.From table 6, there is the composition (sample 1 and sample 2) prepared by the present invention significant anti-inflammatory to suppress to ear swelling
Activity.
Table 7 to the anti-inflammatory inhibiting rate of ear swelling influence (N=10)
Claims (4)
1. it is one kind prevention or treatment chronic obstructive pulmonary disease, allergic rhinitis, chronic bronchitis, acute bronchiolitis, slow
Property pharyngitis the careless composition of silkworm, it is characterised in that by 30~70 parts of silkworm grass, 10~50 parts of Cordyceps militaris and arginine 0.1~10
Part composition.
2. the careless composition of silkworm as claimed in claim 1, its feature is preferably by 50~70 parts of silkworm grass, Cordyceps militaris 30~50
0.1~5 part of composition of part and arginine.
3. a kind of preparation method of the careless composition of silkworm as claimed in claim 1, it is characterised in that comprise the following steps：
A. silkworm grass, Cordyceps militaris, three kinds of raw materials of arginine are first separately dried crushing, mesh number is no less than 20 mesh；
B. the careless composition of the silkworm is uniformly mixed so as to obtain after the powder raw material after crushing is weighed by weight percentage.
4. the preparation method of the careless composition of silkworm according to claim 3, it is characterised in that the silkworm grass, Cordyceps militaris,
The mesh number that arginine raw material is crushed is 20~80 mesh.
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Non-Patent Citations (4)
| Title |
|---|
| L-精氨酸对哮喘的防治作用;余衍亮等;《南京军医学院学报》;20030331;第25 卷(第1 期);14-15 * |
| 不同剂量虫草活力素对大鼠支气管哮喘模型慢性气道炎症的作用机制研究;张旻等;《中华哮喘杂志(电子版)》;20100630;第4 卷(第3 期);191-196 * |
| 左旋精氨酸-氧化氮途径与呼吸系统疾病;王燕等;《小儿息救医学杂志》;19970228;第4 卷(第1期);38-39 * |
| 蚕虫草与有关虫草活性成分检测比较;温 鲁等;《食品科学》;20041231;第25卷(第8期);155-157 * |
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Application publication date: 20150107 Assignee: Liyang Minsheng Agricultural Technology Park Co., Ltd. Assignor: Nanjing Zhuang Biotechnology Co., Ltd.|Jiangsu Academy of Sciences Plant Research Institute of China Contract record no.: 2015320000233 Denomination of invention: Silkworm-cultured cordyceps militaris composition for preventing or treating respiratory disease and application of silkworm-cultured cordyceps militaris composition License type: Common License Record date: 20150416 |
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