CN1215870C - Tenuifolia volatile oil, and formulation preparing method and use in preparing medicine for anti-cold thereof - Google Patents
Tenuifolia volatile oil, and formulation preparing method and use in preparing medicine for anti-cold thereof Download PDFInfo
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Abstract
The present invention discloses a preparation method and pharmacodynamic actions of herba schizonepetae volatile oil and preparations thereof. In the method, herba schizonepetae spikes are taken as raw materials and are made into aqueous herba schizonepetae volatile oil through water addition, distillation and separation; when the aqueous herba schizonepetae volatile oil is froze, ice and water are removed, and the herba schizonepetae volatile oil is obtained; the herba schizonepetae volatile oil as an active substance can be made into various medicament types of capsules (hard capsules and soft capsules) and spraying agents by being added with auxiliary materials in different medicament types. Both of the herba schizonepetae volatile oil and the preparations thereof-jingan capsules and qingfei soft capsules have good effects on resisting inflammation, relieving fever, promoting sudation and resisting bacteria and viruses and also have the advantage of small use dose.
Description
One, technical field
The invention belongs to the field of Chinese medicines, specifically relating to a kind of is the preparation method and the application in preparation treatment Coritab of the medicament active composition that extracts of raw material and preparation thereof with the Chinese crude drug.
Two, background technology
Flu is a kind of common frequently-occurring disease that is caused by cold virus, mainly divides two kinds of common cold and influenzas, and disease comprises fever, headache, myalgia, rhinorrhea, throat pain etc.Flu seems to be " minor illness ", if but treat untimely, cause multiple severe complications easily, as viral myocarditis etc., severe patient also has life danger, especially wherein influenza, it be a kind of sickness rate height of causing by influenza virus, popular extensively, propagate acute respiratory infectious disease rapidly., nineteen fifty-seven in 1918 and nineteen sixty-eight have been broken out big influenza epidemic disease disease 3 times in the whole world, have the tens of millions of people to be seized life by influenza.Because of the surface antigen hemagglutinin HA (Hemagglutinin) of influenza virus and neuraminidase NA (Neuraminidase) can morph constantly, cause cold virus of a great variety, and then give and adopt the vaccine prevention influenza to bring certain difficulty.At present, the number of catching a cold is more and more, and annual winter-spring season all has influenza outbreak several times, so the application of coldrex has extensive market prospects.Although through years of researches, develop some medicines in the world and be used to prevent and treat influenza, the current medicine that is used for the treatment of flu clinically mainly is divided into two kinds in Western medicine and Chinese medicine, Western medicine such as amantadine (amantadine), rimantadine (rimantadine), ribavirin (ribavirin) etc., though have produce effects advantage faster, but side effect is bigger, as disabled because of containing the great PPA of side effect in a lot of Western medicine Coritabs; Comparatively speaking, Chinese medicine and effective ingredient side effect thereof are less, the anti-flu Chinese medicine of Ying Yonging in the market, though curative effect is better, but produce effects is slower, can not satisfy the needs that people's modernization fast pace is lived.
Three, summary of the invention
Up to now, influenza is still the viral infectious of effectively not controlled by the mankind, thereby seeks attention efficient, that anti-influenza virus medicament that have no side effect has obtained countries in the world from plant amedica.So the development of anti-flu new drug has realistic meanings, if can develop a kind of evident in efficacy, novel anti coldrex that side effect is less, will make corresponding contribution to people's medical treatment ﹠ health cause.Under this guiding theory, we are crude drug with traditional diaphoretic medicine Chinese crude drug Herba Schizonepetae, are object of study with its effective site Herba Schizonepetae volatile oil, systematic study Herba Schizonepetae volatile oil and the preparation method of preparation and the application in common cold treatment.
1, goal of the invention: the object of the invention provides a kind of extracting method of Herba Schizonepetae volatile oil for the treatment of flu and the preparation method of preparation thereof,
Chinese crude drug Herba Schizonepetae (Schizonepeta tenuifolia Briq.) is the dry aerial parts of Labiatae annual herb plant Herba Schizonepetae.Herba Schizonepetae is stated from Shennong's Herbal with " false Soviet Union " the earliest, is listed in middle product; The name beginning of Herba Schizonepetae is stated from " WU Pu Bencao ".Warm in nature, the acrid in the mouth of Herba Schizonepetae, also the someone thinks that its property is flat or cool; Its product of giving birth to have expelling pathogenic wind from the body surface, declare malicious rash, the effect of dissipating blood stasis hemostasis, cure mainly anemofrigid cold, laryngopharynx swelling and pain and various skin disease, are the tcm clinical practice common drug.In the recent period, Ding Anwei etc. have carried out systematic research to the Herba Schizonepetae medical material, therefrom extract and obtain one effective site-Herba Schizonepetae volatile oil, pharmacological toxicology experimental verification through system, show that this extract has tangible antiinflammatory, antibiotic, anti-first type and Influenza B virus activity, and have the little advantage of toxic and side effects, the excellent development application prospect is arranged, it can be developed further into effectively anti-flu new drug.
2, technical scheme
Volatile oil extracts the normal methods such as steam distillation, solvent extraction method, supercritical extraction that adopt, wherein steam distillation have easy to operate, with low cost, pollution-free, be applicable to characteristics such as big production, so the present invention adopts steam distillation to extract volatile oil.
A kind of extracting method of Herba Schizonepetae volatile oil, its extraction step is:
(1) takes by weighing Herba Schizonepetae 80～120g, add 8～12 times of amounts of water, vapor distillation 2～8 hours;
(2) with oil water separator separate moisture Herba Schizonepetae volatile oil;
(3) descended freezing 6～36 hours at-9～15 ℃, deicing dewaters, and gets Herba Schizonepetae volatile oil.
A kind of Herba Schizonepetae volatile oil preparation is characterized in that adding the various adjuvants that prepare different dosage form, can be made into capsule (hard capsule, soft capsule), spray and other various preparations with special preparation process.
A kind of preparation method of hard capsule, its preparation process is:
(1) gets the Herba Schizonepetae volatile oil of 1～2g, add the beta-schardinger dextrin-of 6～12 times of amounts and the distilled water of 18～22 times of beta-schardinger dextrin-s, under 25～40 ℃ of conditions,, carry out the medicinal liquid inclusion with dispersion machine high speed dispersion 10～60 minutes;
(2) medicinal liquid after the inclusion is removed adherent volatile oil with spray drying method, spray-dired inlet temperature is 140～180 ℃, and leaving air temp is 60～80 ℃;
(3) with inclusion complex spray powder end, add suitable 95% ethanol, carry out dry granulation, the fill capsule.
A kind of preparation method of soft capsule, its preparation process is:
(1) gets the Herba Schizonepetae volatile oil of 1～2g, add the Polyethylene Glycol-400 of 30～34g and the glycerol of 1～4g, under 25 ~ 40 ℃ of conditions,, carry out medicinal liquid and disperse with stirring 0.5～4 hour;
(2) will disperse back medicinal liquid compacting soft capsule;
(3) soft capsule that suppresses is washed grain with 60～90% ethanol, dried 24～96 hours for 20～40 ℃, promptly.
A kind of spray preparing process, its preparation process is:
(1) gets 1～2g Herba Schizonepetae volatile oil, add 20～40% ethanol and 10%～30% Polyethylene Glycol, be dispersed into the solution shape;
(2) add water 200～400ml, be distributed into oral spray.
With the Herba Schizonepetae volatile oil is raw material, it can be developed to various preparations, and as capsule, spray etc., it is easy to carry that these preparations have, and takes advantages such as easy, also it can be developed to other dosage form.
The application of Herba Schizonepetae volatile oil in preparation treatment anti-cold medicine.
Below in conjunction with the pharmacodynamics test of Herba Schizonepetae volatile oil, further specify beneficial effect of the present invention
(1) the in-vitro antibacterial result of the test shows: the Herba Schizonepetae volatile oil of variable concentrations is to clinical isolates strain Diplococcus pneumoniae, staphylococcus hominis, staphylococcus epidermidis, staphylococcus aureus, middle staphylococcus, kerekou pneumonia hundred Salmonellas, bacillus cloacae, dissolving staphylococcal bacteria, Bacillus alcaligenes, escherichia coli, strange change bacillus, acinetobacter calcoaceticus, streptococcus, group B streptococcus, escherichia coli, Hough Leah bacillus, poly-group bacillus, Bacillus proteus, the abnormal bacillus of plate, section is for staphylococcus, the false monospore bacillus of Bulbus Allii Cepae, aerobacteria and reference culture staphylococcus aureus, escherichia coli, micrococcus luteus, Bacillus pumilus, bacillus subtilises etc. all have certain bacteriostasis, MIC is between 0.625mg～10mg, and prompting: Herba Schizonepetae volatile oil has vitro antibacterial activity.
(2) the antibacterial tests result shows in the body: 1. Herba Schizonepetae volatile oil 10mg/kg, 20mg/kg dosage group can reduce the infection of staphylococcus aureus mouse death rate, with model control group significant difference (P＜0.05, P＜0.01) are arranged relatively.2. Herba Schizonepetae volatile oil 20mg/kg dosage group can reduce Diplococcus pneumoniae infecting mouse mortality rate, and 5mg/kg, 10mg/kg, three dosage groups of 20mg/kg can prolong the survival natural law of infecting mouse; (P＜0.05=prompting: Herba Schizonepetae volatile oil has the certain protection effect to staphylococcus aureus and Diplococcus pneumoniae infecting mouse with model control group significant difference relatively.
(3) the interior resisting virus result of the test shows: 1. Herba Schizonepetae volatile oil 10mg/kg, 20mg/kg dosage group have significant protective effect to influenza A virus (A/PR/8/34) infecting mouse; protective rate is respectively 58.7% and 69.0%; and the time-to-live of influenza a virus infection mice can be prolonged obviously; with model control group significant difference (P＜0.05, P＜0.01=are arranged relatively.2. Herba Schizonepetae volatile oil 5mg/kg, 10mg/kg, 20mg/kg dosage group can obviously reduce the lung exponential quantity of influenza a virus infection mice, with model control group significant difference (P＜0.05 is arranged relatively, P＜0.01=, lung index suppression ratio is respectively 24.4%, 28.9% and 34.2%, the histopathological examination result, Herba Schizonepetae volatile oil has the effect of pulmonary infection disease due to the anti-influenza A virus, the viral infection resisting effect is stronger with Herba Schizonepetae volatile oil 10mg/kg, 20mg/kg effect, and the overall lesion degree of pulmonary is the lightest.Prompting: Herba Schizonepetae volatile oil has the effect that anti-influenza A virus infects.3. Herba Schizonepetae volatile oil 10mg/kg, 20mg/kg dosage group all can obviously prolong the survival natural law of Influenza B virus infecting mouse and reduce Influenza B virus infecting mouse death toll, compare tool significant difference (P＜0.05, P＜0.01=with model control group.4. Herba Schizonepetae volatile oil 10mg/kg, 20mg/kg dosage group all can obviously reduce the lung exponential quantity of Influenza B virus infecting mouse, lung index suppression ratio is 23.23% and 22.87%, and prompting: Herba Schizonepetae volatile oil has the effect that alleviates Influenza B virus infecting mouse pulmonary lesion.Prompting: Herba Schizonepetae volatile oil has significant protective effect to the Influenza B virus infecting mouse.
(4) the antiinflammatory result of the test shows: 1.: Herba Schizonepetae volatile oil 10mg/kg, 20mg/kg can reduce auricle swelling degree due to the dimethylbenzene, with model group notable difference (P＜0.05, P＜0.01) are arranged relatively.2. Herba Schizonepetae volatile oil 10mg/kg, 20mg/kg can reduce the increase of the optical density value of the mouse peritoneal eluate due to the acetic acid, and (prompting: Herba Schizonepetae volatile oil has certain antiinflammatory action for P＜0.05, P＜0.01=with model group notable difference relatively.
(5) diaphoresis, analgesic result of the test show: 1. Herba Schizonepetae volatile oil 10mg/kg can reduce that rat temperature raises due to the dry yeast, with model group notable difference (P＜0.05) is arranged relatively.2. Herba Schizonepetae volatile oil 6mg/kg can reduce that rabbit body temperature raises due to the endotoxin, with model group notable difference (P＜0.05, P＜0.01) is arranged relatively.3. Herba Schizonepetae volatile oil 5mg/kg, 10mg/kg can promote the secretion of rat toes sweat gland, with model group notable difference (P＜0.05, P＜0.01) are arranged relatively.Prompting: Herba Schizonepetae volatile oil has necessarily analgesic, perspiration.
In sum: Herba Schizonepetae volatile oil has preferably antiinflammatory, analgesic, diaphoresis, antibiotic and antivirus action.
3, beneficial effect
(1) Herba Schizonepetae volatile oil is the effective site extracted from Chinese medicine, and have preferably antiinflammatory, analgesic, diaphoresis, antibiotic and antivirus action: 1. the in-vitro antibacterial result of the test shows that Herba Schizonepetae volatile oil has vitro antibacterial activity.2. the antibacterial tests result shows that Herba Schizonepetae volatile oil has the certain protection effect to staphylococcus aureus and Diplococcus pneumoniae infecting mouse in the body.3. the interior resisting virus result of the test shows that Herba Schizonepetae volatile oil has anti-first type, the Influenza B virus infecting mouse has significant protective effect.4. the antiinflammatory result of the test shows that Herba Schizonepetae volatile oil has certain antiinflammatory action.5. diaphoresis, analgesic result of the test show that Herba Schizonepetae volatile oil has necessarily analgesic, perspiration.
(2) Herba Schizonepetae volatile oil has the little advantage of dosage.Its mice effective dose is 10mg/kg, 20mg/kg.
(3) Herba Schizonepetae volatile oil has the little advantage of toxic and side effects, its mice LD
50Be 560mg/kg, 95% the credible 514mg/kg～609mg/kg that is limited to.
(4) be that raw material is made and adopted the homogenizing dispersing technology in the inclusion technology of hard capsule with the Herba Schizonepetae volatile oil, this technology can shorten the inclusion time greatly, improves inclusion efficient.
(5) drying process among the hard capsule preparation technology adopts drying process with atomizing, and this technology can be removed adherent volatile oil, improves semi-finished product and stability of formulation.
Four, the specific embodiment
The extracting method of embodiment 1, Herba Schizonepetae volatile oil, its extraction step is:
(1) gets Herba Schizonepetae 3.31kg, add 10 times of water gagings, vapor distillation 6 hours;
(2) with oil water separator separate moisture Herba Schizonepetae volatile oil 33.0g;
(3)-12 ℃ freezing 24 hours, deicing dewaters, Herba Schizonepetae volatile oil 31.5g, promptly.
The preparation method of embodiment 2, hard capsule chaste tree-Jingan capsule of the present invention, its preparation process is:
(1) get Herba Schizonepetae volatile oil 31.5g, the beta-schardinger dextrin-(252g) of 8 times of amounts of adding and the distilled water (5.04L) of 20 times of beta-schardinger dextrin-s are used dispersion machine high speed dispersion 30 minutes under 30 ℃ of conditions;
(2) the inclusion medicinal liquid adopts spray drying, and 160 ℃ of inlet temperature are set, and 70 ℃ of leaving air temps get inclusion complex spray powder end;
(3) every 250g spray powder spray adds 10ml95% ethanol, dry granulation, and 1000 of fill capsules, every dress 0.25g, promptly.
Embodiment 3, soft capsule of the present invention-clear luxuriant and rich with fragrance preparation of soft capsule method, its preparation process is:
(1) gets the Herba Schizonepetae volatile oil of 2g, add the Polyethylene Glycol-400 of 31.35g and the glycerol of 1.65g, under 30 ℃ of conditions,, carry out medicinal liquid and disperse with stirring 2 hours;
(2) compacting of the medicinal liquid after will disperseing soft capsule;
(3) soft capsule that suppresses is washed grain with 75% ethanol, dried 72 hours for 25 ℃, promptly.
The preparation method of embodiment 4, oral spray the steps include:
(1) gets the 1.2g Herba Schizonepetae volatile oil, add 30% ethanol and 10% Polyethylene Glycol, be dispersed into the solution shape;
(2) add water 200ml, be distributed into oral spray.
Embodiment 5, Jingan capsule pharmacodynamics test
1 experiment material
1.1 medicine and reagent
Jingan capsule, off-white powder, every 1g beta-cyclo dextrin included compound contains volatile oil 0.084g, and lot number is provided by Nanjing University of Traditional Chinese Medicine: 20011220, face the time spent to be formulated into desired concn with distilled water.
Beta-schardinger dextrin-: China Medicine's lot number: 20010308
Ciprofloxacin Guangzhou Nan Xin pharmaceutical Co. Ltd lot number 011102
Ribavirin capsule Zhejiang-new pharmaceutical Co. Ltd lot number 010105
SHUANGHUANLIAN: Song Hua River, Harbin pharmaceutical factory lot number 001014
Prospirolboli joannsi chemical plant, ether Shanghai lot number 980209
Chemical plant, granary, sodium chloride Jiangsu lot number 990901
Chemical plant, the Taishan, picric acid Guangdong lot number 990623
Nutrient broth Shanghai City medical science assay office lot number 010927
Nutrient agar Shanghai City medical science assay office lot number 010324
Jiangning, sheep red blood cell (SRBC) Nanjing epidemic prevention station lot number 020505
Gastric Mucin: provide by microbial room of China Medicine University
Dimethylbenzene: Shanghai chemical reagent purchasing and supply station is sold lot number 010121
Glacial acetic acid: Nanjing chemical reagent factory lot number 010317
Ivens orchid: China Medicine's lot number 010213
Three nine-day periods after the winter solstice cold drug: Sanjiu Pharmaceutical Co., Ltd's lot number: 20010609
Aspirin: Astra (Wuxi) pharmaceutical Co. Ltd lot number: 20020110
Endotoxin: U.S. Sigma company lot number: L-2630 Lot 31k4121
Dry yeast: Hubei Angel Yeast Co.,Ltd's lot number: 20020518
Dehydrated alcohol: the Shanghai chemical reagent company limited lot number of anticipating for a long time: 20010520
Iodine: Chinese Chengdu chemical reagent factory lot number: 010314
Oleum Ricini: chemical reagent station, Shanghai packing factory lot number: 010623
Field-Gao Shi reagent A liquid: get iodine 2 gram and be dissolved in the 100ml dehydrated alcohol.
Field-Gao Shi reagent B liquid: get soluble starch 50 grams, Oleum Ricini 100ml, both get final product by uniform mixing.
1.2 laboratory animal:
The ICR mice is provided by Nanjing Medical University's Experimental Animal Center, qualified lot number: SCZK (Soviet Union) 2001-0015
Kunming mouse, SD rat are provided by Nanjing University of Traditional Chinese Medicine's Experimental Animal Center, the laboratory animal quality certification number: moving (matter) 97003 of Soviet Union, laboratory animal occupancy permit number: SYXK (Soviet Union) 2002-0053, experimental animal feeding credit number: SCXK (Soviet Union) 2002-0012
Rabbit: by Xian Tangshan Green Dragon mountain, Jiangning animal reproduction factory, experimental animal feeding credit number: SCXK (Soviet Union) 2002-0027
1.3 experiment bacterial strain and Strain
Reference culture:
Staphylococcus aureus (26003), escherichia coli (44104), short and small bacillocin (63202), bacillus subtilis (63501), micrococcus luteus (28001) are provided by the Ministry of Public Health microbial identification.
The clinical isolates strain:
Staphylococcus aureus, escherichia coli, bacillus pyocyaneus, acinetobacter calcoaceticus, kerekou pneumonia hundred Salmonellas, staphylococcus epidermidis, staphylococcus hominis, the false monospore bacillus of Bulbus Allii Cepae, citric acid enterobacteria, very become bacillus, aerobacteria, the abnormal bacillus of plate, a poly-group bacillus, dissolving staphylococcal bacteria, Diplococcus pneumoniae, group B streptococcus, middle staphylococcus, Hough Leah bacillus at streptococcus, Bacillus proteus, and section is for staphylococcus, Bacillus alcaligenes, provided by Jiangsu Prov. People's Hospital microbial room isolation identification.
Strain: influenza A virus A/PR/8/34, the anti-98-76 in Influenza B virus B/ capital is provided by Virology Inst., China Academy of Preventive Medicine Sciences.
2 experiment conditions and statistical method
2.1 experiment condition
Before and after the administration, experiment mice sub-cage rearing full-valence pellet feed is provided by Jiangpu, Nanjing development laboratory animal feed factory, the quality certification number: moving (raising) word 96001 of Soviet Union, freely drink water 22 ± 2 ℃ of room temperatures, humidity 55-60%.
2.2 statistical method
Statistics adopt t check, X
2Check.
3 experimental techniques and result:
3.1 the vitro antibacterial activity of Jingan capsule
[1] [4]
3.1.1 increasing bacterium cultivates
Get each bacterial strain a little, in the inoculation broth bouillon, cultivate 18h for 37 ℃, take out and be diluted to 10 with NS
-5Standby.
3.1.2 the pastille plate preparation
Depletion sense capsule 32g adds to and is melted up to mixing (320mg/ml) in 60 ℃ of 100ml agar culture mediums, with two times of methods be diluted to 160mg, 80mg, 40mg, 20mg, 10mg, 5mg, 2.5mg, 1.25mg 0.625mg, 0.313mg, 0.156mg/ml series concentration pastille plate is stand-by.Get ciprofloxacin injection and agar culture medium mixing, also make final concentration with doubling dilution and be: the serial pastille plate of 128 μ g, 64 μ g, 32 μ g, 16 μ g, 8 μ g, 4 μ g, 2 μ g, 1 μ g, 0.5 μ g, 0.25 μ g, 0.125 μ g, 0.0625 μ g, 0.0313 μ g/ml is stand-by.
3.1.3 the mensuration of antibacterial activity in vitro MIC
Make a call to 3 holes with the aseptic steel ring of 6mm on above-mentioned serial pastille plate, every hole is injected bacteria containing amount and is about 10
-5CFUml, 0.1ml cultivates 18～20h for 37 ℃, is medicine with the least concentration of contained drug in the asepsis growth plate culture medium minimum inhibitory concentration (MIC) of this bacterium be the results are shown in Table 1
Table 1: the antibacterial activity in vitro of Jingan capsule (n=2)
| Bacterial strain MIC Jingan capsule (mg/ml) ciprofloxacin (μ g/ml) |
| Staphylococcus 02-3 1.25mg 1 μ g kerekou pneumonia hundred Salmonella 02-1 2.5mg 0.0625 μ g kerekou pneumonia hundred Salmonella 02-2 10mg 0.0313 μ g kerekou pneumonia hundred Salmonella 02-3 1.25mg 0.0313 μ g bacillus cloacae 02-1 5mg 2 μ g bacillus cloacae 02-2 2.5mg 1 μ g bacillus cloacae 02-3 10mg 1 μ g dissolving staphylococcal bacteria 02-1 10mg 8 μ g Bacillus alcaligenes 02-1 2.5mg 8 μ g among the staphylococcus 02-2 5mg 0.25 μ g among the staphylococcus 02-1 2.5mg 2 μ g among the Diplococcus pneumopniae 02-1 5mg 0.0313 μ g people staphylococcus 02-1 5mg 0.25 μ g table staphylococcus 02-1 1.25mg 0.125 μ g staphylococcus aureus 02-1 1.25mg 0.5 μ g staphylococcus aureus 02-2 1.25mg 1.0 μ g staphylococcus aureus 02-3 0.625mg 0.25 μ g |
| Bacterial strain MIC Jingan capsule (mg/ml) ciprofloxacin (μ g/ml) |
| 02-1 1.25mg 2μg 02-2 5mg 2μg 02-3 5mg 2μg 02-1 1.25mg 0.25μg 02-2 5mg 0.25μg 02-1 80mg 2μg 02-2 80mg 2μg 02-1 5mg 1μg 02-2 1.25mg 1μg 01-1 2.5mg 0.125μg 01-4 1.25mg 1μg ( ) 2.5mg 0.125μg 01-1 2.5mg 0.125ug ( ) 1.25mg 0.125μg 01-4 2.5mg 2μg ( ) 1.25mg 0.5μg ( ) 1.25mg 1μg ( ) 1.25mg 0.5μg 01-1 1.25mg 1μg 01-1 1.25mg 1μg 01-1 1.25mg 0.125μg 01-1 0.625mg 0.125μg 01-1 0.625mg 0.0313μg 01-1 5mg 8μg |
Shown in the experimental result: Jingan capsule is to standard gold Staphylococcus aureus, escherichia coli, micrococcus luteus.Bacillus pumilus, bacillus subtilis and clinical isolates Diplococcus pneumoniae, staphylococcus hominis, staphylococcus epidermidis, staphylococcus aureus, middle staphylococcus, kerekou pneumonia hundred Salmonellas, bacillus cloacae, dissolving staphylococcal bacteria, Bacillus alcaligenes, escherichia coli, strange change bacillus, acinetobacter calcoaceticus, streptococcus, group B streptococcus, escherichia coli, Hough Leah bacillus, poly-group bacillus, Bacillus proteus, the abnormal bacillus of plate, section is for staphylococcus, the false monospore bacillus of Bulbus Allii Cepae, aerobacteria has stronger bacteriostasis, MIC is between 0.625mg-10mg, and prompting: Jingan capsule has vitro antibacterial activity.
3.2 the vivo bacteria corrosion action of Jingan capsule
3.2.1 the preparation of staphylococcus aureus bacterium liquid:
Depletion Staphylococcus aureus bacterial strain is chosen a little in nutrient broth medium with inoculating loop, puts 37 ℃ of incubators and cultivates 18h.Take out, line on the blood plate, 37 ℃ of incubators are cultivated 18h, take out, with the gastric Mucin eluting bacterium colony of 6ml 5%, with normal saline be made into 0.75ml/ml, 0.25ml/ml, 0.15ml/ml, 0.083ml/ml concentration bacterium liquid is standby.
3.2.2 infection of staphylococcus aureus mouse death rate preliminary experiment
Get 40 of ICR mices, ♀ ♂ half and half, body weight 18--22g random packet, every group of 1 concentration, lumbar injection staphylococcus aureus bacterium liquid, 0.5ml/ Mus observed the infecting mouse death toll, and the infecting mouse mortality rate is respectively 100%, 100% as a result, and 90%, 70%.0.11ml/ml concentration bacterium liquid is selected in experiment for use.
3.2.3 protective effect to the infection of staphylococcus aureus mice
Get 126 random packet of 18-22g ICR kind mice, 21 every group, ♀ ♂ dual-purpose.(1) blank group: equivalent beta-schardinger dextrin-20ml/kg (2) model control group: equivalent beta-schardinger dextrin-20ml/kg.(3) SHUANGHUANLIAN group: 20ml/kg.(4) Jingan capsule I group: 5mg/kg.(5) Jingan capsule II group 10mg/kg.(6) Jingan capsule III group 20mg/kg.Below respectively organize the equal gastric infusion of mice, irritate gastric capacity 20ml/kg, 1 time/day * 5 days, administration was after 1 hour in the 3rd day, 0.5ml/ Mus of lumbar injection staphylococcus aureus culture fluid (remove blank group) continues administration 2 days, observes that death condition the results are shown in Table 2 in each treated animal 7 days
Table 2: Jingan capsule is to the protective effect of infection of staphylococcus aureus decimal death
| Group number of animals dosage death toll survival rate survival natural law (only) is (only) (%) (P value of x ± S) (g/kg) |
| Blank group 21-1 model control group 21-17 19.04 3.35 ± 2.24 SHUANGHUANLIAN groups 21 20ml 9 57.14 *5.00 ± 2.43 p＜0.05 Jingan capsule I organizes 21 0.005 10 52.38 4.86 ± 2.44 p＞0.05 Jingan capsule II and organizes 21 0.010 9 57.14 *5.10 ± 2.35 p＜0.05 Jingan capsule III organizes 21 0.020 7 66.67 ** 5.232.43 p＜0.05 |
Model control group relatively
*P＜0.05
*P＜0.05
Shown in the experimental result: Jingan capsule 10mg/kg and 20mg/kg dosage group can to the infection of staphylococcus aureus mice
Reduce the survival natural law that its mortality rate also can prolong infecting mouse; Relatively have significant difference (P＜0.05, P＜0.01) prompting with model group: Jingan capsule has significant protective effect to the infection of staphylococcus aureus mice.
3.2.4 the preparation of Diplococcus pneumoniae bacterium liquid:
Get the Diplococcus pneumoniae bacterial strain, choose a little in nutrient broth medium, put 37 ℃ of incubators and cultivate 18h with inoculating loop.Take out, line on the blood plate, 37 ℃ of incubators are cultivated 18h, take out, and the gastric Mucin eluting bacterium colony with 6ml 5% is made into 1ml/ml with normal saline, 0.5ml/ml, and 0.33ml/ml, 0.25ml/ml concentration bacterium liquid is standby.
3.2.5 the preliminary experiment of Diplococcus pneumoniae infecting mouse mortality rate:
Get 40 of ICR mices, ♀ ♂ half and half, body weight 18--22g random packet, every group of 1 concentration, lumbar injection Diplococcus pneumoniae bacterium liquid, 0.5ml/ Mus only, observe the infecting mouse death toll, the infecting mouse mortality rate is respectively 100.0%, 90.0% as a result, 0.5ml/ml concentration bacterium liquid is selected in 60.0%, 40.0% experiment for use.
3.2.6. Jingan capsule is to the protective effect of Diplococcus pneumoniae infecting mouse death.
Get 126 random packet of 18-22g ICR kind mice, 21 every group, ♀ ♂ dual-purpose.(1) blank group: equivalent beta-schardinger dextrin-20ml/kg (2) model control group: equivalent beta-schardinger dextrin-20ml/kg.(3) SHUANGHUANLIAN group: 20ml/kg.(4) Jingan capsule I group: 5mg/kg.(5) Jingan capsule II group 10mg/kg.(6) Jingan capsule III group 20mg/kg.Below respectively organize the equal gastric infusion of mice, irritate gastric capacity 20ml/kg, 1 time/day * 5 days, administration was after 1 hour in the 3rd day, 0.5ml/ Mus of lumbar injection Diplococcus pneumoniae culture fluid (remove blank group) continues administration 2 days, observes that death condition the results are shown in Table 3 in each treated animal 7 days
Table 3: Jingan capsule is to the protective effect of Diplococcus pneumoniae infecting mouse death
| Group number of animals dosage death toll survival rate survival natural law (only) is (only) (%) (P value of x ± S) (g/kg) |
| Blank group 21-0 model control group 21-19 9.5 1.81 ± 1.74 SHUANGHUANLIAN groups 21 20ml 12 42.9 *3.81 ± 2.81 p＜0.05 Jingan capsule I organizes 21 0.005 13 38.1 3.52 ± 2.75 p＜0.05 Jingan capsule II and organizes 21 0.010 13 38.1 3.71 ± 2.62 p＜0.05 Jingan capsule III and organize 21 0.020 12 42.9* 3.95±2.95 p＜0.05 |
Compare * P＜0.05**P＜0.01 with model control group
Shown in the experimental result: Jingan capsule 20mg/kg dosage group can reduce its mortality rate to the Diplococcus pneumoniae infecting mouse, Jingan capsule 5mg/kg, and 10mg/kg and 20mg/kg dosage group can prolong the survival natural law of infecting mouse; (P＜0.05=prompting: Jingan capsule has the certain protection effect to the Diplococcus pneumoniae infecting mouse relatively to have significant difference with model control group.
3.3 the interior resisting virus effect of Jingan capsule
[2] [3]
3.3.1 protective effect to the influenza a virus infection mice
(1) hemagglutination test
Get 36 hole microwell plates, every hole adds normal saline 0.25ml.First hole adds 10
-1Virus allantoic fluid 0.25ml behind the mixing, gets 0.25ml successively and puts second hole, is diluted to the 9th hole.The tenth hole does not add viral allantoic fluid, compares.Every hole adds 0.5% chicken red blood cell 0.25ml, and shake up the back gently and place 2 hours observed results in room temperature, the record result, hemagglutination test (HA) is 640.
(2) influenza a virus infection mice median lethal dose(LD 50) (LD
50) titration.
Get 49 of ICR mices, body weight 13-15g, the male and female dual-purpose divides 7 groups at random, every group 7, get and increase 3 times viral allantoic fluid of poison, with 10 times of dilutions, every group drips a virus concentration, each organize mice under the ether light anaesthesia with viral allantoic fluid 30ul collunarium, observe death toll in 14 days, press Reed and Muench method and calculate, as a result LD
50Be 2.90
3.3.2 Jingan capsule is to the protective effect of influenza a virus infection mice
Get 174 of ICR mices, body weight 12-16g, male and female half and half, divide 6 groups at random, 29 every group (1) blank groups: equivalent beta-schardinger dextrin-10ml/kg (2) model control group: equivalent beta-schardinger dextrin-10ml/kg (3) ribavirin group: 75mg/kg (4) Jingan capsule I group: 5mg/kg (5) Jingan capsule II group: 10mg/kg (6) Jingan capsule III group: 20mg/kg, under the ether light anaesthesia, with the allantoic fluid of hemagglutination test more than 640, infect every Mus 30ul, (20 LD for the mice collunarium
50Lethal dose), observes zoogenetic infection sequela and death condition, the results are shown in Table 4.
Table 4. Jingan capsule is to the protective effect of influenza a virus infection dead mouse
| Group number of animals dosage death toll mortality rate protective rate survival natural law (only) is (only) (%) (%) (x ± s) (mg/kg) |
| The blank group: 29--model control group 29-21 72.4 27.6 8.58 ± 3.55 ribavirin group 29 75 8 27.5 72.5 ** 10.38±2.71 **Jingan capsule I organizes 29 5 14 48.2 51.8 10.933.58 *Jingan capsule II organizes 29 10 12 41.3 58.7 * 11.17±3.50 *Jingan capsule III organizes 29 20 9 31.0 69.0 ** 12.31±3.72 ** |
Compare with the virus control group
*P＜0.05
*P＜0.01
Shown in the experimental result: Jingan capsule 5mg/kg, 10mg/kg and 20mg/kg dosage group all can obviously prolong the survival natural law of influenza a virus infection mice; (P＜0.05; P＜0.01=10mg/kg and 20mg/kg dosage group can significantly reduce influenza a virus infection dead mouse number; compare tool significant difference (P＜0.05, P＜0.01) prompting with model control group: Jingan capsule has significant protective effect to the influenza a virus infection mice.
3.3.3 Jingan capsule is to the exponential influence of influenza a virus infection mouse lung
Get 100 of ICR mices, body weight 13-16g, ♂ ♀ half and half.Divide 5 groups at random, 20 every group.(1) model control group: equivalent beta-schardinger dextrin-10ml/kg (2) ribavirin group: 75mg/kg (3) Jingan capsule I group: 5mg/kg (4) Jingan capsule II group: 10mg/kg (5) Jingan capsule III group: 20mg/kg, below respectively organize the equal gastric infusion of mice, irritated gastric capacity 20ml/kg 1 time/day * 7 days, respectively organized mice (except that the blank group) on the 3rd day in administration, under the ether light anaesthesia with viral allantois drop nose infecting mouse, every Mus 30ul (15 LD
50Challenging dose).Continued administration 4 days, water is can't help in fasting before the experiment, and experiment was respectively organized mice and weigh the same day, taking off neck puts to death, dissect, observe pulmonary lesion, get full lung and weigh, calculate each Mus lung exponential quantity, lung index suppression ratio compares each group difference, and gets lung 10% formaldehyde fixed, do the pathology histological examination, the results are shown in Table 5.
Table 5: Jingan capsule is to the exponential influence of influenza a virus infection mouse lung (x ± s)
| Group dosage number of animals lung exponential quantity lung index suppression ratio (mg/kg) (only) is (%) (g/10g) |
| Model control group-20 0.1676 ± 0.055 ribavirin group 75 20 0.1075 ± 0.017 **35.86 Jingan capsule I organizes 5 20 0.1267 ± 0.034 *24.40 Jingan capsule II organizes 10 20 0.1175 ± 0.019 **29.89 Jingan capsule III organizes 20 20 0.1103 ± 0.020 ** 34.19 |
Compare with the virus control group
*P＜0.05
*P＜0.01
Shown in the experimental result:
(1) Jingan capsule 5mg/kg, 10mg/kg and 20mg/kg dosage group all can obviously reduce the lung exponential quantity of influenza a virus infection mice, lung index suppression ratio is 24.40%, 29.89% and 34.19, and prompting: Jingan capsule has the effect that alleviates influenza a virus infection mouse lung pathological changes.
(2) shown in the report of pulmonary's pathological examination.
1. influenza A virus pneumonia model group: slight bronchitis, interstitial pneumonia 1 example.The moderate purulent bronchitis, bronchiolitis and interstitial pneumonia change 3 examples.The visible degeneration of bronchial epithelial cell, necrosis, the more visible purulent exudates of intracavity.The lung tissue segment structure is unclear, is the consolidation shape.There are more neutrophil cell, macrophage, lymphocytic infiltration in the consolidation district.The lobate distribution of above-mentioned change effect.Consolidation district peripheral part alveolar wall thickens, and a small amount of above-mentioned cell infiltration is also seen in vasodilation hyperemia in it, and the fraction alveolar ectasia is the edema due to disorder of QI shape.The severe purulent bronchitis, bronchiolitis and interstitial pneumonia have changed 5 examples.Bronchial epithelial cell degeneration, necrosis, the visible more purulent exudate of intracavity.Lung tissue structure is unclear on every side for the lobule bubble around the pathological changes bronchus, and a large amount of neutrophil cells, lymphocytic infiltration are arranged.The part pathological changes merges consolidation.Consolidation district peripheral part alveolar wall thickens, vasodilation in it, and a matter has the above-mentioned cell infiltration that more or less.The part alveolar ectasia is the edema due to disorder of QI shape.Utmost point severe purulent bronchitis, bronchiolitis and interstitial pneumonia have changed 1 example.The obvious degeneration of bronchial epithelial cell, necrosis, the visible a large amount of purulent exudates of intracavity.Large stretch of lung tissue structure is unclear around the pathological changes bronchus, is the consolidation shape, and there are a large amount of neutrophil cells, macrophage, lymphocytic infiltration in the consolidation district.Consolidation district peripheral part alveolar wall thickens, and its interior blood vessel is obviously expanded, hyperemia, and a matter has more above-mentioned cell infiltration.The part alveolar ectasia is the edema due to disorder of QI shape.
2. ribavirin group: slight bronchitis, interstitial pneumonia 7 examples.Moderate purulent bronchitis, bronchiolitis and interstitial pneumonia 3 examples.
3. Jingan capsule small dose group: slight bronchitis, interstitial pneumonia 4 examples.Moderate purulent bronchitis, bronchiolitis and interstitial pneumonia 6 examples.
4. dosage group in the Jingan capsule: slight bronchitis, interstitial pneumonia 7 examples.
Moderate purulent bronchitis, bronchiolitis and interstitial pneumonia 3 examples.
5. Jingan capsule is heavy dose of organizes: slight bronchitis, interstitial pneumonia 6 examples.Moderate purulent bronchitis, bronchiolitis and interstitial pneumonia 4 examples.
The The above results prompting:
Influenza a virus infection duplicates the mouse lung infectious disease, can form the purulent bronchitis of various degree, lobule apex pulmonis and interstitial pneumonia.Jingan capsule has the effect of pulmonary infection disease due to the anti-influenza A virus.
3.3.4 protective effect to the Influenza B virus infecting mouse.
(1) hemagglutination test
Get 36 orifice plates, every hole adds normal saline 0.25ml.First hole adds 10
-1Virus allantoic fluid 0.25ml behind the mixing, gets 0.25ml successively and puts second hole, is diluted to the 9th hole.The tenth hole does not add viral allantoic fluid, compares.Every hole adds 0.5% chicken red blood cell 0.25ml, and shake up the back gently and place 2 hours observed results in room temperature, the record result, hemagglutination test (HA) is 640.
(2) the anti-98-76 infecting mouse median lethal dose(LD 50) (LD in Influenza B virus B/ capital
50) titration.
Get 49 of ICR mices, body weight 13-15g, the male and female dual-purpose divides 7 groups at random, every group 7, get and increase 3 times viral allantoic fluid of poison, with 10 times of dilutions, every group drips a virus concentration, each organize mice under the ether light anaesthesia with viral allantoic fluid 30ul collunarium, observe death toll in 14 days, press Reed Muench method and calculate, as a result LD
50Be 2.60.
3.3.5 Jingan capsule is to the protective effect of the anti-98-76 infecting mouse in Influenza B virus B/ capital
Get 174 of ICR mices, body weight 12-16g, male and female half and half, divide 6 groups at random, 29 every group (1) blank groups: equivalent beta-schardinger dextrin-10ml/kg (2) virus control group: equivalent beta-schardinger dextrin-10ml/kg (3) ribavirin group: 75mg/kg (4) Jingan capsule I group: 5mg/kg (5) Jingan capsule II group: 10mg/kg (6) Jingan capsule III group: 20mg/kg, under the ether light anaesthesia, with the allantoic fluid of hemagglutination test more than 640, infect every Mus 30ul, (20 LD for the mice collunarium
50Lethal dose), observes zoogenetic infection sequela and death condition, the results are shown in Table 6.
Table 6: Jingan capsule is to the protective effect of Influenza B virus infecting mouse death
| Group number of animals dosage death toll mortality rate protective rate survival natural law (only) is (only) (%) (%) (x ± s) (mg/kg) |
| The blank group: 19-0 model control group 19-18 95.0 5.0 7.16 ± 2.28 Ribavirin groups, 19 75 10 52.6*, 47.4 10.74 ± 3.18** Jingan capsule I organize 19 5 12 63.2 36.8 9.42 ± 3.68* Jingan capsule II and organize 19 10 10 52.6*, 47.4 10.68 ± 3.36** Jingan capsule III and organize 19 20 10 52.6*, 47.4 10.21 ± 3.75** |
Compare with model control group
*P＜0.05
*P＜0.01
Shown in the experimental result: Jingan capsule 10mg/kg and 20mg/kg dosage group all can obviously prolong the survival natural law of Influenza B virus infecting mouse and reduce Influenza B virus infecting mouse death toll; compare tool significant difference (P＜0.05, P＜0.01) prompting with model control group: Jingan capsule has significant protective effect to the Influenza B virus infecting mouse.
3.3.6 Jingan capsule is to the influence of Influenza B virus Lung Index of mice infected by Influenza virus
Get 100 of ICR mices, body weight 13-16g, ♂ ♀ half and half.Divide 5 groups at random, 20 every group.(1) model control group: equivalent beta-schardinger dextrin-10ml/kg (2) ribavirin group: 75mg/kg (3) Jingan capsule I group: 5mg/kg (4) Jingan capsule II group: 10mg/kg (5) Jingan capsule III group: 20mg/kg, below respectively organize the equal gastric infusion of mice, irritated gastric capacity 20ml/kg 1 time/day * 5 days, respectively organized mice (except that the blank group) on the 2nd day in administration, under the ether light anaesthesia with viral allantois drop nose infecting mouse, every Mus 30ul (20 LD
50Challenging dose).Continued administration 4 days, water is can't help in fasting before the experiment, and experiment was respectively organized mice and weigh the same day, taking off neck puts to death, dissect, observe pulmonary lesion, get full lung and weigh, calculate each Mus lung exponential quantity, lung index suppression ratio compares each group difference, and gets lung 10% formaldehyde fixed, do the pathology histological examination, the results are shown in Table 7.
Table 7: Jingan capsule is to the influence of Influenza B virus Lung Index of mice infected by Influenza virus (x ± s)
| Group dosage number of animals lung exponential quantity lung index suppression ratio (mg/kg) (only) is (%) (g/10g) |
| Blank group-16 0.0999 ± 0.009 model control group-14 0.1679 ± 0.047 ribavirin group 75 16 0.1210 ± 0.034 **27.93 Jingan capsule I organizes 5 16 0.1479 ± 0.039 11.91 Jingan capsule II and organizes 10 16 0.1289 ± 0.032 **23.23 Jingan capsule III organizes 20 16 0.1295 ± 0.036 * 22.87 |
Compare with model control group
*P＜0.05
*P＜0.01
Shown in the experimental result:
(1) Jingan capsule 10mg/kg and 20mg/kg dosage group all can obviously reduce the lung exponential quantity of Influenza B virus infecting mouse, lung index suppression ratio is 23.23% and 22.87%, and prompting: Jingan capsule has the effect that alleviates Influenza B virus infecting mouse pulmonary lesion.
(2) result of histopathologic examination: see accompanying drawing 14-29.
1. normal control group: 10 routine lung tissues all are normal morphology.No exudate in the bronchial lumen, mucosal epithelium does not have degeneration necrosis and comes off, and tube wall and surrounding tissue thereof do not have cell infiltration: alveolar septum does not thicken, no cell infiltration, no exudate in the alveolar space.
2. model group: this organize all lung tissues all be in to severe bronchitis and interstitial pneumonia, and congested, hemorrhage more obvious, 1/3 lung tissue is mild to moderate alveolitis.Show as bronchial epithelial cell degeneration, necrosis, intracavity is seen non-viable non-apoptotic cell and exudate.Pathological changes bronchial wall and lung tissue structure is unclear on every side has volume lymphocyte, macrophage and a small amount of neutrophil cell to soak into.Alveolar wall generally thickens, vasodilation in it, and the above-mentioned cell infiltration that more or less is arranged, wherein visible apoptotic body in the lung tissue segment alveolar.
3. ribavirin group: this is organized 7 routine lung tissues and is mild to moderate bronchitis and interstitial pneumonia, and 2 examples are heavier, and 1 example is normal substantially.Overall lesion degree is lighter than model group.
4. low dose group: this group lung tissue also is mild to moderate bronchitis and interstitial pneumonia, and the minority case is heavier.But overall lesion degree is lighter than model group
5. middle dosage group: this group pathological change form is similar to low dose group, and overall lesion degree is slightly light.
6. high dose group: this group pathological change form is respectively organized similarly to above-mentioned, but overall lesion degree obviously is lighter than above-mentioned each administration group.Wherein 3 examples are normal substantially.
Conclusion:
Influenza B virus infects and successfully duplicates the mouse lung inflammatory lesion.Mainly show as bronchitis and interstitial pneumonia.
Herba Schizonepetae has the effect of pulmonary infection disease due to the anti-Influenza B virus, and the high dose curative effect is better.
3.4 Jingan capsule is to the antiinflammatory action of mice
3.4.1 the antiinflammatory action of the ear swelling due to the Jingan capsule xylol
[5]
50 of Male Kunming strain mice, body weight 25-30g is divided into 5 groups at random by body weight, 10 every group.(1) model control group: give isopyknic beta-schardinger dextrin-; (2) aspirin group: 600mg/kg; (3) Jingan capsule I group: 5mg/kg; (4) Jingan capsule II group: 10mg/kg; (5) Jingan capsule III group: 20mg/kg; Administration volume 20ml/kg behind each dosage group ig on same day administration 45min of Jingan capsule, is coated with dimethylbenzene 0.05ml/ and only causes swollenly in the mouse right ear two sides, left ear is not painted with normal ear.Take off cervical vertebra behind the 45min and put to death mice, lay disk in same area respectively, scales/electronic balance weighing, every Mus auris dextra weight-left ear weight=swelling degree with the 9mm punching.The results are shown in Table 8.
Table 8 Jingan capsule xylol causes the antiinflammatory action (X ± S) of mice ear
| Group | Number of animals (only) | Dosage (mg/kg) | Auricle swelling degree (mg) | Inhibitory rate of intumesce (%) |
| Model control group aspirin group Jingan capsule I group Jingan capsule II group Jingan capsule III group | 10 10 10 10 10 | -- 600 5 10 20 | 0.0147±0.0029 0.0045±0.0048 ** 0.0154±0.0037 0.0114±0.0033 * 0.0105±0.0031 ** | ---- 69.39％ -4.76％ 22.45％ 28.57％ |
Compare with model control group,
*P＜0.05,
*P＜0.01
The result shows: Jingan capsule 10mg/kg, 20mg/kg dosage group can be resisted dimethylbenzene induced mice ear swelling, with model control group relatively have significant difference (
*P＜0.05).Prompting: Jingan capsule has certain antiinflammatory action.
3.4.2 the influence that Jingan capsule Dichlorodiphenyl Acetate induced mice abdominal cavity capillary permeability increases
[6]
50 of Male Kunming strain mice are divided into 5 groups at random by body weight, 10 every group.(1) model control group: give isopyknic beta-schardinger dextrin-; (2) aspirin group: 600mg/kg; (3) Jingan capsule I group: 5mg/kg; (4) Jingan capsule II group: 10mg/kg; (5) Jingan capsule III group: 20mg/kg; Administration volume 20ml/kg, behind each dosage group ig on same day administration 45min of Jingan capsule, tail vein injection 0.5% azovan blue normal saline solution 0.1ml/10g, lumbar injection 0.6% acetic acid 0.1ml/10g immediately is behind the 20min, broken end sacrificed by exsanguination mice, cut off the abdominal cavity, with 5ml normal saline flushing abdominal cavity for several times, collect cleaning mixture, centrifugal (1000rpm) 5min measures trap (OD value) at ultraviolet spectrophotometer 590nm place.The results are shown in Table 9.
Table 9 Jingan capsule Dichlorodiphenyl Acetate causes the influence that the mice capillary permeability increases (X ± S)
| Group | Number of animals (only) | Dosage (mg/kg) | Trap (OD value) |
| Model control group aspirin group Jingan capsule I group Jingan capsule II group Jingan capsule III group | 10 10 10 10 10 | -- 600 5 10 20 | 0.248±0.088 0.128±0.049 ** 0.235±0.099 0.147±0.067 * 0.133±0.062 ** |
Compare with model control group,
*P＜0.05,
*P＜0.01
The result shows: Jingan capsule 10mg/kg, 20mg/kg dosage group can suppress acetic acid induced mice abdominal cavity capillary permeability to be increased, with model control group relatively have significant difference (
*P＜0.05).Prompting: Jingan capsule has certain antiinflammatory action.
3.5 analgesic, the perspiration of Jingan capsule
3.5.1 Jingan capsule is to the influence of rat fever due to the dry yeast
[8]
Get 70 body weight 200 ± 20g of SD rat and place experimental situation, test preceding 2 day set time and measure rat anus temperature once with clinical thermometer, choose the rat of body temperature fluctuation in 36.6 ℃-38.3 ℃ of normal ranges, fasting is 12 hours before experiment, can freely drink water, and the same day was surveyed body temperature 2 times in experiment, every 2 hours once, select the temperature difference to be no more than 0.3 ℃ 50 of qualified rats, be divided into 5 groups at random by body weight, 10 every group.(1) model control group: give isopyknic beta-schardinger dextrin-; (2) aspirin group: 300mg/kg; (4) Jingan capsule I group: 2.5mg/kg; (4) Jingan capsule II group: 5mg/kg; (5) Jingan capsule III group: 10mg/kg, administration volume 20ml/kg, behind the gastric infusion at once in rat back subcutaneous injection dry yeast (15%) suspension 10ml/kg, survey its anus temperature value in the moment of 1h, 2h, 4h, 6h, 8h, 10h then, gastric infusion is once obtained each and is measured the changing value of moment body temperature with respect to normal body temperature again behind rat back subcutaneous injection dry yeast (15%) suspension 4h, as vertical coordinate, with time is abscissa, and the body temperature situation of change is observed in mapping.See Table 10.
Table 10 Jingan capsule is to the influence of rat fever due to the dry yeast (X ± S)
| Group | Number of animals (only) | Dosage (mg/kg) | Body temperature before the medicine (℃) | Body temperature (Δ ℃) | |||||
| 1h | 2h | 4h | 6h | 8h | 10h | ||||
| Model control group aspirin group Jingan capsule I group Jingan capsule II group Jingan capsule III group | 10 10 10 10 10 | - 300 2.5 5 10 | 37.24±0.4 37.51±0.41 7.50±0.57 37.54±0.28 37.50±0.47 | 37.96±0.58 (0.71±0.60) 37.69±0.34 (0.18±0.32) 38.01±0.56 (0.51±0.42) 38.45±0.48 (0.90±0.36) 38.05±0.33 (0.55±0.29) | 38.22±0.57 (0.97±0.59) 37.72±0.35 * (0.21±0.41 **) 38.20±0.47 (0.70±0.40) 38.43±0.32 (0.88±0.32) 37.94±0.48 (0.44±0.34*) | 39.11±0.51 (1.86±0.38) 37.67±0.29 ** (0.16±0.38 **) 38.86±0.63 (1.36±0.84) 39.23±0.48 (1.68±0.60) 38.81±0.60 (1.31±0.63*) | 39.86±0.33 (2.61±0.54) 37.97±0.34 ** (0.46±0.58 **) 39.75±0.80 (2.25±0.73) 40.02±0.47 (2.47±0.53) 39.41±0.67 (1.91±0.75*) | 39.51±0.56 (2.26±0.77) 37.82±0.33 ** (0.31±0.46 **) 39.47±0.78 (1.97±0.78) 39.48±0.32 (1.93±0.48) 39.25±0.69 (1.75±0.95) | 39.46±0.65 (2.21±0.85) 37.67±0.37 ** (0.16±0.37 **) 39.33±0.86 (1.83±0.85) 39.35±0.29 (1.80±0.44) 39.31±0.74 (1.81±1.05) |
Compare with model control group,
*P＜0.05,
*P＜0.01
Show: Jingan capsule 10mg/kg can reduce that rat temperature raises due to the dry yeast, with model control group notable difference is arranged relatively, and the prompting Jingan capsule has certain reduction body temperature effect.
3.5.2 Jingan capsule is to the influence of fever in rabbits due to the endotoxin
[9]
Select for use the healthy rabbits about body weight 2kg to place experimental situation, test preceding 2 day set time and measure rabbit anus temperature once with clinical thermometer, choose the rabbit of 38.5 ℃-39.5 ℃ of body temperature, behind the auricular vein injection endotoxin 1h, select 40 of the fever in rabbit of the temperature difference above 1.0 ℃, divide 5 groups at random, (1) model control group: give isopyknic beta-schardinger dextrin-; (2) aspirin group: 300mg/kg; (3) Jingan capsule I group: 6mg/kg; (4) Jingan capsule II group: 3mg/kg; (5) Jingan capsule III group: 1.5mg/kg, gastric infusion, administration volume 1ml/kg, survey its anus temperature value in the moment of 1h, 2h, 3h, 4h, 5h, 6h then, obtain each and measure the changing value of moment body temperature, as vertical coordinate with respect to normal body temperature, with time is abscissa, the body temperature situation of change is observed in mapping, sees Table 11.
Table 11 Jingan capsule is to the influence of fever in rabbits due to the endotoxin (X ± S)
| Group | Number of animals (only) | Dosage (mg/kg) | Body temperature before the medicine (℃) | Body temperature behind the medicine (Δ ℃) | |||||
| 1h | 2h | 3h | 4h | 5h | 6h | ||||
| Model control group aspirin group Jingan capsule I group Jingan capsule II group Jingan capsule III group | 8 8 8 8 8 | - 300 1.5 3 6 | 39.10±0.19 39.21±0.11 39.22±0.12 39.06±0.23 39.26±0.10 | 40.52±0.39 (1.42±0.35) 40.22±0.16 (1.02±0.22 *) 40.80±0.45 (1.58±0.49) 40.60±0.47 (1.54±0.41) 40.86±0.34 (1.60±0.31) | 40.90±0.48 (1.80±0.50) 40.20±0.28 ** (0.99±0.35 **) 40.81±0.46 (1.59±0.47) 40.65±0.32 (1.59±0.25) 40.74±0.33 (1.47±0.33) | 41.22±0.37 (2.12±0.37) 40.31±0.68 ** (1.11±0.75 **) 41.31±0.59 (2.09±0.60) 41.02±0.46 (1.97±0.50) 40.62±0.52 * (1.36±0.52 **) | 40.72±0.59 (1.62±0.58) 40.00±0.62 * (0.77±0.69 *) 40.75±0.60 (1.53±0.54) 40.44±0.55 (1.38±0.54) 40.14±0.44 (0.87±0.47 *) | 40.19±0.49 (1.08±0.50) 39.61±0.38 * (0.41±0.44 *) 40.16±0.49 (0.94±0.43) 39.90±0.34 (0.84±0.33) 39.81±0.48 (0.55±0.53) | 39.72±0.39 (0.62±0.41) 39.35±0.21 * (0.14± 0.21 *) 39.78±0.42 (0.56±0.34) 39.52±0.33 (0.47±0.35) 39.49±0.26 (0.22±0.30) |
Compare with model control group,
*P＜0.05,
*P＜0.01
The result shows: Jingan capsule 6mg/kg can reduce rabbit fervescence due to the endotoxin, with model control group notable difference is arranged relatively, and the prompting Jingan capsule has certain reduction body temperature effect.
3.5.3 Jingan capsule is to the influence of rat toes portion sweat secretion
[10]
Get 50 of the close male rats of body weight, observe vola portion respectively and have or not dirt,, dip in cotton swab and to get dehydrated alcohol scrub gently if any dirt.Be divided into 5 groups at random, (1) model control group: give isopyknic beta-schardinger dextrin-; (2) three nine-day periods after the winter solstice cold drug group: 500mg/kg; (3) Jingan capsule I group: 10mg/kg; (4) Jingan capsule II group: 5mg/kg; (5) Jingan capsule III group: 2.5mg/kg, administration volume 20ml/kg behind the gastric infusion 45min, places homemade big rat holder internal fixation respectively, exposes two lower limb, wipes away the perspiration of doing due to original and the struggle gently with dried cotton swab.Coat and field-Gao Shi reagent A liquid respectively at every Mus toes portion skin then.After treating intensive drying, the very thin again B liquid of coating is observed darkviolet colored spots (being the antiperspirant point) with magnifier then, and what rat was perspired in the record 5min counts, and sees Table 12.Take off rat one parapodum after the observation immediately, use 10% formalin fixed, do the pathology histological examination, observe and respectively organize the variation of rat sweat gland epithelial cell.
Table 12 Jingan capsule is to the influence of rat toes portion sweat secretion (X ± S)
| Group | Number of animals (only) | Dosage (mg/kg) | Perspire in the 5min and count |
| Model control group three nine-day periods after the winter solstice cold drug group Jingan capsule I group Jingan capsule II group Jingan capsule III group | 10 10 10 10 10 | -- 500 2.5 5 10 | 186.4±63.42 288.0±66.42 ** 238.6±88.31 263.6±81.59 * 262.8±41.66 ** |
Compare with model control group,
*P＜0.05,
*P＜0.01
Pathological examination is as follows, and sees accompanying drawing 30～34.
1. model control group: a rat skin of respectively drawing materials is complete, and subcutaneous sweat gland organizational structure is clear intact, and surrounding tissue does not have obviously hemorrhage and cell infiltration.
2. three nine-day periods after the winter solstice cold drug group: a rat skin of respectively drawing materials is complete, and subcutaneous sweat gland organizational structure is clear intact, and sweat gland acinus number is significantly increased (++-+++) than model group, and surrounding tissue does not have obviously hemorrhage and cell infiltration.
3. small dose group: the subcutaneous sweat gland organizational structure of respectively drawing materials is clear intact, and sweat gland acinus number increases (+-++) to some extent than model group, and surrounding tissue does not have obviously hemorrhage and cell infiltration.
4. middle dosage group: a rat skin of respectively drawing materials is complete, and subcutaneous sweat gland organizational structure is clear intact, and sweat gland acinus number increases same small dose group (+-++), and surrounding tissue does not have obviously hemorrhage and cell infiltration.
5. heavy dose of group: a rat skin of respectively drawing materials is complete, and subcutaneous sweat gland organizational structure is clear intact, and sweat gland acinus number is significantly increased (++-+++), and surrounding tissue does not have obviously hemorrhage and cell infiltration.
Experimental result shows: Jingan capsule 20mg/kg, 10mg/kg dosage can promote the secretion of rat toes sweat gland, with model control group significant difference are arranged relatively, and the prompting Jingan capsule has certain promotion perspiration.
List of references
[1] Qi Chen chief editor " herbal pharmacology research methodology ", People's Health Publisher, Beijing 2000, P251, P275
[2] Liu Jingsong, Qi Fang port, He Rui etc.The research of the anti-oral liquid antivirus action of chaste tree, Pharmacology and Clinics of Chinese Materia Medica 1998,14 (1): 41
[3] Du Ping chief editor " medical experimental virusology " People's Medical Officer Press, Beijing 1985,9, front page P111
[4] Zhu Xuan tawny daylily, Xu Li, the clear anti-bacteria and anti-virus experimentation of the safe favour lung poison in side, new Chinese medicine and clinical pharmacology 2001 (12) 4 P263
[5] Qi Chen chief editor. herbal pharmacology experimental technique, the 1st edition. Beijing: People's Health Publisher 1994:70
[6] Qi Chen chief editor. herbal pharmacology experimental technique, the 1st edition. Beijing: People's Health Publisher 1994:72
[7] Qi Chen chief editor. herbal pharmacology experimental technique, the 1st edition. Beijing: People's Health Publisher 1994:107
[8] Qi Chen chief editor. herbal pharmacology experimental technique, the 1st edition. Beijing: People's Health Publisher 1994:52
[9] Li Yikui, Wang Qinmao. herbal pharmacology experimental methodology [M]. Shanghai: the Shanghai science and technology goes out the .1991.311-313 of society
[10] Qi Chen chief editor. herbal pharmacology experimental technique, the 1st edition. Beijing: People's Health Publisher 1994:46
Claims (4)
1, a kind of extracting method of Herba Schizonepetae volatile oil is characterized in that being extracted by the following step:
(1) takes by weighing Herba Schizonepetae 80～120g, add 8～12 times of amounts of water, vapor distillation 2～8 hours;
(2) with oil water separator separate moisture Herba Schizonepetae volatile oil;
(3) descended freezing 6～36 hours at-9～15 ℃, deicing dewaters, and gets Herba Schizonepetae volatile oil.
2, a kind of preparation method of hard capsule of Herba Schizonepetae volatile oil, its preparation process is:
(1) gets the Herba Schizonepetae volatile oil that the described method of 1～2g claim 1 is extracted, add the beta-schardinger dextrin-of 6～12 times of amounts and the distilled water of 18～22 times of beta-schardinger dextrin-s, under 25～40 ℃ of conditions, use dispersion machine high speed dispersion 10～60 minutes, carry out the medicinal liquid inclusion;
(2) medicinal liquid after the inclusion is removed adherent volatile oil with spray drying method, spray-dired inlet temperature is 140～180 ℃, and leaving air temp is 60～80 ℃;
(3) with inclusion complex spray powder end, add suitable 95% ethanol, carry out dry granulation, the fill capsule.
3, a kind of preparation method of soft capsule of Herba Schizonepetae volatile oil, its preparation process is:
(1) gets the Herba Schizonepetae volatile oil that the described method of 1～2g claim 1 is extracted, add the Polyethylene Glycol-400 of 30～34g and the glycerol of 1～4g, under 25～40 ℃ of conditions,, carry out medicinal liquid and disperse with stirring 0.5～4 hour;
(2) will disperse back medicinal liquid compacting soft capsule;
(3) soft capsule that suppresses is washed grain with 60～90% ethanol, dried 24～96 hours for 20～40 ℃.
4, a kind of spray preparing process of Herba Schizonepetae volatile oil, its preparation process is:
(1) gets the Herba Schizonepetae volatile oil that the described method of 1～2g claim 1 is extracted, add 20～40% ethanol and 10%～30% Polyethylene Glycol, be dispersed into the solution shape;
(2) add water 200～400ml, be distributed into oral spray.
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| CN 03132166 CN1215870C (en) | 2003-07-04 | 2003-07-04 | Tenuifolia volatile oil, and formulation preparing method and use in preparing medicine for anti-cold thereof |
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| CN 03132166 CN1215870C (en) | 2003-07-04 | 2003-07-04 | Tenuifolia volatile oil, and formulation preparing method and use in preparing medicine for anti-cold thereof |
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| CN1215870C true CN1215870C (en) | 2005-08-24 |
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| CN101428125B (en) * | 2008-12-19 | 2011-06-29 | 成都青山利康药业有限公司 | Medicament composition with antiviral efficacy |
| CN112402489A (en) * | 2020-12-18 | 2021-02-26 | 陕西中医药大学 | Schizonepeta spike wind-dispelling ointment |
| CN113662986A (en) * | 2021-09-17 | 2021-11-19 | 驻马店市中洋生物科技有限公司 | Method for preparing catnip oil from catnip essential oil extracted from catnip plant |
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Application publication date: 20040414 Assignee: QIONGLAI TIANYIN PHARMA Co.,Ltd. Assignor: Nanjing University of Chinese Medicine Contract record no.: 2018610000007 Denomination of invention: Tenuifolia volatile oil, and formulation preparing method and use in preparing medicine for anti-cold thereof Granted publication date: 20050824 License type: Exclusive License Record date: 20180314 |
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