CN1602886A - Pharmaceutical compositions and its application - Google Patents
Pharmaceutical compositions and its application Download PDFInfo
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- CN1602886A CN1602886A CN 03135947 CN03135947A CN1602886A CN 1602886 A CN1602886 A CN 1602886A CN 03135947 CN03135947 CN 03135947 CN 03135947 A CN03135947 A CN 03135947A CN 1602886 A CN1602886 A CN 1602886A
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Abstract
The invention provides a drug combination and its use, and it is a preparation made from fibrauretin, baicalin and pharmaceutically acceptable carrier. And the medicine effect test proves that fibrauretin and baicalin in it match with each other to achieve synergism and have the effects of resisting viruses, antibiosis, reducing fever, resisting imflammation, etc and provides a new clinic drug for selection.
Description
Technical field
The invention provides a kind of medical composition and its use, specifically, is the pharmaceutical composition of being made up of fibrauretin, baicalin that has broad-spectrum antiviral, antibacterium and improve the effect of immune function of human body.
Figure viewed from behind technology
The data that provides according to " the national hospital infection monitoring system " of health ministry tissue shows, the patient who is in hospital every year in the whole nation is about 5,000 ten thousand people, and wherein about 5,000,000 people are for infecting the class patient.Wherein respiratory tract infection accounts for the first place, is 30%, is urinary system infection secondly, accounts for 19%.
Respiratory tract infection is divided into upper respiratory tract infection and lower respiratory infection.Upper respiratory tract infection mainly refers to the above position of larynx, comprises nose, pharynx, larynx etc., and the disease that comprises has flu, pharyngitis, tonsillitis, laryngitis etc., is divided into acute upper respiratory tract infection and chronic upper respiratory tract infection.Acute upper respiratory tract infection is commonly called as " flu ", is the general name by viral or bacterial nose, pharynx, acute throat inflammation, is the stronger disease of the modal a kind of infectiousness of respiratory tract, good sending out in winter-spring season.According to cause of disease difference, can be divided into viral and bacillary two big classes.Viral infection accounts for the 70-80% of acute upper respiratory tract infection, cause by rhinovirus, influenza virus, parainfluenza virus, adenovirus, respiratory syncytial virus, Coxsackie virus, echovirus, coronavirus etc. that mainly clinical manifestation mostly is common cold, influenza, viral pharyngitis, viral laryngitis, pharyngoconjunctival fever, herpetic pharyngitis etc.; Bacterial infection mainly causes by Jia Xingrongxuexinglianqiujun, streptococcus pneumoniae, staphylococcus, hemophilus influenza etc., be secondary to viral infection more after, minority is for directly being caused by antibacterial, clinical manifestation mostly is bacillary pharynx one tonsillitis etc.According to statistics, catch a cold 2-5 time for each person every year, the child can reach more than 6 times, and the people that flu is died from the whole world every year reaches more than 2,000,000.Often suffer from the people of acute upper respiratory tract infection, Abwehrkraft des Koepers descends once again, forms chronic respiratory tract infection, as chronic pharyngitis etc., but and the multiple disease of secondary, as acute nephritis, myocarditis, rheumatism etc., endanger healthy.Lower respiratory infection mainly is meant the position that larynx is following, the inflammation that comprises trachea, bronchus, bronchioles and lung tissue positions such as (comprising alveolar and interstitial lung), clinical manifestation is acute/chronic bronchitis, lobar pneumonia, bronchopneumonia and chronic laryngitis etc., mostly be, as gram negative bacteria, streptococcus pneumoniae etc. by bacterial.It is a kind of commonly encountered diseases, frequently-occurring disease that the urinary tract system infects.Abroad, urinary tract infection accounts for more than 33% of hospital infection class patient, and domestic sickness rate is also high always.The main pathogenic bacterium that cause urinary tract infection have escherichia coli, staphylococcus aureus and Pseudomonas aeruginosa etc., in recent years, suppressed by brute force or kill because the antibiotic life-time service of high-efficiency broad spectrum causes in the body profitable strain, cause dysbacteriosis, fungoid urinary tract infection is in rising trend.Drug main at respiratory tract infection and the infection of urinary tract system will be based on broad-spectrum antibiotic.
At present, generally select for use suitable antibiotic such as penicillin, erythromycin etc. to treat to bacterial respiratory tract infection, but bacterial drug resistance increases gradually in recent years, especially streptococcus pneumoniae, abroad have report to the resistant rate of benzylpenicillin up to more than 50%, escherichia coli and staphylococcus to the drug resistance of quinolones also up to more than 50%; Show according to online search data, the Wuxi City, Jiangsu Province crowd to the drug resistance of penicillium communne element up to 82%, to the drug resistance of pioneer's generation cefazolin sodium up to 43% (the healthy net in Feihua).To viral upper respiratory tract infection, because virus can only parasitize in the host cell, require antiviral drugs can import cell into, selectivity suppresses the propagation of virus, simultaneously do not damage host cell again, the progress of adding Western medicine is slower, poor specificity, side effect is big, so still there is not ideal antiviral Western medicine up to now.Bibliographical information is arranged, the urinary system infection that escherichia coli causes, use ciprofloxacin, ampicillin, cefazolin sodium, bactrim, its resistant rate is up to 75% (153 routine urinary system infection due to Escherichia coli analyses, Sun Jun etc., China basic unit medicine, 2002,9 (11)), also have the bibliographical information antibiotic to lack curative effect for many urinary tract infections, main cause still is that bacterial antibiotic has produced certain drug resistance, makes can carry out treating second time (37 ℃ of medical science nets) in some patients 28 days after treatment first.
Studies show that in a large number, from the antibiotic and antiviral active substance of natural drug, because the complexity of itself is difficult for causing antibacterial and viral drug resistance.From Chinese medicine, screen broad-spectrum antibiotic, become the important means of drug research.
Research at present, fibrauretin is the total alkaloids that Caulis Fibraureae (Fibraurea recisa) ratan and root extract, and wherein contains palmatine (Palmatine), jateorhizine (Jatrorrhizine), Columbamine (columbamine), fibranine (Fibranine), fibraminine (fibraminine), fibralactone (Fibralactone), sterol (C
27H
45OH) etc.Palmatine is called palmatine again, and (English: Palmatine), be the main component in the medical material Caulis Fibraureae, content about 3% in the medical material, and the content of palmatine can reach more than 97.25% in fibrauretin, molecular formula: [C
21H
22NO
4]
+352.4 mostly palmatine is to extract from Caulis Fibraureae in the market, also contains a small amount of palmatine in other plant such as Cortex Phellodendri, Rhizoma Coptidis, the Caulis Mahoniae.Palmatine (palmatine) belongs to benzylisoquinoline class quaternary amine alkaloid, in water, has certain dissolubility, its sulfate or the acetate dissolubility in water is big, and the halogen acid salt dissolubility is less, slightly water-soluble, effect with heat-clearing and toxic substances removing, multiple leather Lan Shi negative bacterium and leather Lan Shi positive bacteria there is inhibitory action, and effect with enhancing leukocytes phagocytic ability, be used for the treatment of upper respiratory tract infection, tonsillitis, enteritis, dysentery, urinary tract infection, eye conjunctivitis, surgery and gynecological's bacterial infection inflammation (Luo Liangui. the improvement of palmatine extraction process. Chinese Journal of Pharmaceuticals, 1990,021 (004): 155-156).
Baicalin, another name: baicalin, baicalin derive from the dry root of medical material Radix Scutellariae Scutellariabaicalensis Georgi, molecular formula: C
21H
18O
11, water-soluble hardly, be insoluble in methanol, ethanol, acetone, dissolve in hot acetic acid.Meet ferric chloride and show green, meet lead acetate and generate salmon precipitation, effects such as heat-clearing and toxic substances removing, inhibiting bacteria and diminishing inflammation, adjusting immunity, conformable metallic ion, blood pressure lowering, antiallergic action are arranged, be usually used in treating hepatitis, hypertension, infection etc.
According to Chinese medical theory, the heat that mostly is the said epidemic febrile disease of the traditional Chinese medical science by virus, bacteriogenic disease such as acute infectious diseases, acute infectious disease is gone into the nutrient blood stage, and pathogenic warmth is attacked outward.Its pathogenesis is: pathogenic warmth is gone into from mouth and nose, violates lung meridian earlier, defends branch and stands in the breach.Body healthy energy is risen vigorously anti-evil, and so struggle between vital QI and pathogen is heating.Evil Yu Feiwei, failure of skin and muscle to be nourished is aversion to cold then, and pathogenic warmth is that YANG pathogen is so aversion to cold is lighter and of short duration.Heresy is stayed the flesh table, defends to be subjected to heresy strongly fragrant, must not stretch space between skin and muscles folding mistake department, then hypohidrosis or lossless.Pathogenic warmth is attacked table, and so positive hot pathogen upward attacking orifices in head is headache.Lung is subjected to evil strongly fragrant, and clear respectful duty mistake department then coughs.The pathogenic warmth impairment of body fluid is then thirsty.Pathogenic warmth is by defending that branch imports into or pathogenic warmth is directly violated the bright or edema caused by disorder of QI latent heat is sent out or battalion's heat the is gone out edema caused by disorder of QI of sun outward, and edema caused by disorder of QI is turned round for the pivot that the epidemic febrile disease pathogenesis lapses in a word.Sun is bright to be sea of the twelve channels, is the passages through which vital energy circulates of the many blood of many gas, and anti-evil power is strong.Strive acutely so pathogen invading YANG MING, good and evil are handed over, so interior-heat is steamed and is compeled the whole body high fever.The temperature pathogen in the interior is at table, so aversion to cold and only generating heat not.So excessive heat in the interior, heat burn body fluid thirst and liking cold drink.Heat is compeled the body fluid then hyperhidrosis that leaks.At above-mentioned pathogenesis, the method for treatment that the traditional Chinese medical science adopts is: its heat clearly, separate its poison, and the invasion of blocking-up pathogenic warmth is also displaced body with it.
Chinese medicine Caulis Fibraureae, Radix Scutellariae, this two flavors drug matching, the Caulis Fibraureae bitter in the mouth is cold in nature, and the function heat-clearing and toxic substances removing is monarch drug.The Radix Scutellariae bitter cold has the effect of heat-clearing and toxic substances removing, pathogenic fire purging dampness and the excess-heat of kind clear part of the body cavity above the diaphragm housing the heart and lungs cardiopulmonary, is ministerial drug, auxiliary Caulis Fibraureae heat-clearing and toxic substances removing.Return through main through, Caulis Fibraureae from returning that Radix Scutellariae then returns lung, middle Jiao to return the taste large intestine channel Jiao at part of the body cavity above the diaphragm housing the heart and lungs heart channel and part of the body cavity below the umbilicus, housing the bladder, kidneys and bowels Liver and kidney warp, the two is harmonious, and the upper, middle and lower three warmers all have and relate to, and each is got clearly through pathogenic warmth.
Fibrauretin, baicalin are respectively from Chinese medicine Caulis Fibraureae, Radix Scutellariae, and effective ingredient complexity in the Chinese medicine is used fibrauretin, baicalin compatible combination separately, does not still have relevant report at present.From the natural drug raw material, filter out have broad-spectrum antiviral, the antibacterial medicine, have good value for clinical application and market prospect.
Summary of the invention
In order to address the above problem, technical scheme of the present invention provides by fibrauretin, the pharmaceutical composition that baicalin is formed, and another technical scheme of the present invention provides the purposes of this pharmaceutical composition.
The invention provides a kind of pharmaceutical composition, it is the preparation of being made by fibrauretin fibranine, baicalin baicalin and pharmaceutically acceptable carrier.
Wherein the weight proportion of fibrauretin, baicalin is: fibrauretin 2.5-100 part, and baicalin 5-100 part, further, the weight proportion of fibrauretin, baicalin is: 5 parts of fibrauretin, 5 parts of baicalins.
Above-mentioned fibrauretin Fibrauretin derives from menispermaceous plants Caulis Fibraureae Fibraurea recisaPierre rattan and root, and baicalin baicalin derives from the dry root of labiate Radix Scutellariae Scutellariabaicalensis Georgi.
Wherein said preparation is a solid preparation, liquid preparation, and further, described preparation is injection, capsule, tablet, micropill, eye drop, granule.
The present invention also provides the purposes of this pharmaceutical composition in preparation broad-spectrum antiviral, antimicrobial medicine, further, provides the purposes of this pharmaceutical composition in analgesic, the antiphlogistic medicine of preparation.
The present invention also provides the purposes of this pharmaceutical composition in the medicine of preparation raising immunity.
The present invention uses fibrauretin, baicalin compatibility, at antiviral, antibiotic, analgesic, antiinflammatory, raising immunology, has brought into play the effect of Synergistic; Compare with the pharmacodynamics test of independent use arbitrary material wherein, medicine of the present invention has than significant inhibitory effect propagation and the caused mice pneumonia thereof of influenza virus; Try leather Lan Shi positive bacteria, leather Lan Shi negative bacterium all there is external antibacterial and bactericidal action in various degree; Typhoid fever, paratyphoid fever triple vaccine are caused that the fervescence of rabbit has the obvious suppression effect, and longer duration, medication still has after 4 hours and separates thermal effect; Inductive mice ear of xylol and rat Oleum Terebinthinae air bag granulation hyperplasia significant inhibitory effect all arranged, illustrate that medicine of the present invention all has therapeutical effect to acute, subacute inflammation; By measuring the influence of cleaning up index, HD50 element and T lymphocyte transformation function of medicine of the present invention, prove that medicine of the present invention can significantly improve nonspecific immunity and the specific immune function of mice to mice.Prove absolutely two compounds compatibilities in the medicine of the present invention, reach Synergistic, have antiviral, antibiotic, analgesic, antiinflammatory, raising immunization, provide a kind of new medication to select for clinical.
Obviously, according to foregoing of the present invention,,, can also make modification, replacement or the change of other various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.
The specific embodiment of form is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
The specific embodiment
Below prove beneficial effect of the present invention by the specific embodiment.
The extraction of embodiment 1 fibrauretin
Get menispermaceous plants Caulis Fibraureae Gaullis Fibraureae Recisae rattan and root coarse powder 100g, add 10 times of amount 2%H
2SO
4Aqueous solution boils 30min, inclining supernatant, filters, and medicinal residues repeat to extract once, merging filtrate, transferring pH with 40%NaOH solution is 10, adds 10% refining NaCL simultaneously, heat 80 ℃ and be incubated 30min, placed sucking filtration, drying 24 hours, promptly get fibrauretin, wherein the content requirement of palmatine is 〉=95%.
The extraction of embodiment 2 baicalins
Get the dry root coarse powder of labiate Radix Scutellariae Scutellaria baicalensis Georgi, add 10 times of amounts respectively, 8 times of water gagings decoct 2 times, each 1 hour, filter, filtrate is added HCL adjust pH 1-2,80 ℃ of insulation 30min, leave standstill, centrifugal must the precipitation got precipitation and added suitable quantity of water and stir evenly, add 40%NaOH and transfer to pH value 7, add equivalent ethanol, filter, filtrate adds HCL adjust pH 1-2, fully stir, be heated to 80 ℃ of insulation 30min, filter, must precipitate, to precipitate washing, 50% washing with alcohol, reuse 95% washing with alcohol or recrystallization get baicalin.
The preparation of embodiment 3 medicine capsules of the present invention
Take by weighing baicalin 30g, fibrauretin 20g adds an amount of magnesium stearate and silicon dioxide, abundant mixing, and filled capsules, 1000, sterilization, promptly.The clinical drug needs according to the present invention are selected raw material baicalin, fibrauretin and the different adjuvants of different quality for use, can prepare the capsule of different size.
The preparation of embodiment 4 medicinal tablets of the present invention
Take by weighing baicalin 40g, fibrauretin 25g adds an amount of sodium carboxymethyl cellulose, microcrystalline Cellulose, and tabletting is made 1000, sterilization, promptly.The clinical drug needs according to the present invention are selected raw material baicalin, fibrauretin and the different adjuvants of different quality for use, can prepare the tablet of different size.
The preparation of embodiment 5 medicine eye drop of the present invention
Take by weighing baicalin 8g and fibrauretin 5g, use 8% sodium hydroxide solution and dissolved in distilled water respectively, add 0.6g sodium chloride and an amount of antiseptic again, adding distil water is to 100ml, and transferring pH value is 6.0, and be distributed into 8ml/ and prop up, sterilization, promptly.The clinical drug needs according to the present invention are selected raw material baicalin, fibrauretin and the different adjuvants of different quality for use, can prepare the eye drop of different size.
The preparation of embodiment 6 drug injections of the present invention
Take by weighing baicalin 10g and fibrauretin 5g, use sodium hydroxide solution and dissolved in distilled water respectively, add an amount of isoosmotic adjusting agent and antiseptic again, fully dissolving, adding distil water is to 1000ml, and the adjusting pH value is 5.5-7.5, sterilization, promptly.The clinical drug needs according to the present invention are selected raw material baicalin, fibrauretin and the different adjuvants of different quality for use, can prepare the injection of different size.
The preparation of embodiment 7 medicinal dropping balls of the present invention
Polyethylene glycol 6000/4000 are heated to whole fusions in water-bath, add baicalin and fibrauretin, stir, and insulation is at 80 ℃, splash in 5 ℃ the liquid Paraffin to become ball.The clinical drug needs according to the present invention are selected raw material baicalin, fibrauretin and the different adjuvants of different quality for use, can prepare the drop pill of different size.
Below prove beneficial effect of the present invention by concrete pharmacodynamics test.
Experimental example 1, drug injection interior resisting virus of the present invention test
1. experiment material
1.1 medicine:
A, medicaments injection of the present invention: press the method preparation of embodiment 6, yellowish-brown clear liquid, specification: 2ml/ prop up (every ml contains 5mg baicalin and 5mg fibrauretin).
B, baicalin for injection liquid: the brownish red clear liquid, self-control, specification: every ml contains baicalin 10mg.
Preparation method: precision takes by weighing baicalin 10g, and the sodium hydroxide solution with 8% dissolves in right amount, adds water to 980ml, regulate pH value to 7.2 with 8% sodium hydroxide solution, it is an amount of to add active carbon, puts in the water-bath and heats 1 hour, filter, put coldly, add benzyl alcohol 10ml, be adjusted to 1000ml with water for injection, filter, embedding, sterilization, promptly.
C, fibrauretin injection:
Xanchromatic clear liquid; The accurate word Z53020075 of traditional Chinese medicines; 2ml/ props up; Specification: 2ml: 20mg (every 1ml is equivalent to fibrauretin 10mg); Lot number: 030202; Produce by Yunnan China fir elm pharmaceutical Co. Ltd.
1.2 animal and grouping
90 of Kunming mouses, body weight 14～15g, male and female half and half, Chengdu University of Traditional Chinese Medicine's Experimental Animal Center provides.Be divided at random and infect each two groups of matched groups, baicalin group, fibrauretin group, medicine group of the present invention, one group of normal control group, 10 every group.
1.3 virus
Influenza virus A-prime Mus lung adapted strain FM
1, viral seed culture of viruses uses after Chengdu University of Traditional Chinese Medicine's Pathology Lab goes down to posterity available from West China Center of Medical Sciences of Sichuan University institute of viruses, and-70 ℃ of preservations are standby.
2 experimental techniques
2.1 effect to mice influenza virus property pneumonia
Except that normal group, mice is slightly anaesthetized with ether, with 15 LD
50Influenza virus liquid (FM1) collunarium infects.Begin intraperitoneal injection the previous day from infecting, 0.1ml/10g, continuous 5 days, wherein infects matched group and the normal control group gives with the volume normal saline at every day 2 times.Dissected after taking by weighing the mice body weight on the 6th day, win full lung and weigh, calculate the lung exponential quantity one by one, and obtain lung index suppression ratio.Formula:
Heavy (the g)/body weight (g) * 100 of lung index=lung
Lung index suppression ratio %=(virus control group lung index average-test group lung index average)/virus control group lung index average * 100%
Annotate: the lung index is big, and expression lung weight is big, and pneumonopathy range degree is serious.
2.2 influence to proliferation of influenza virus amount in the mouse lung
Removing the viral infection amount is 1000LD
50Outward, medication is the same.48 hours outer dead mices are dissected and get lung behind the viral infection, win left side middle period lung and fix, and press the conventional dehydration of pathological section, embedding, making paraffin section.With indirect immunofluorescence dyeing, do the spike source with fluorescein-labeled infection serum virus, 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.
3 statistical method
Data are represented with x ± s, adopt the t check, the comparable group differences.
4 results and analysis
4.1 effect to mice influenza virus property pneumonia
As shown in table 1, infect back mouse lung exponential quantity and obviously increase.The pneumonia that medicaments injection of the present invention causes the influenza virus infecting mouse has obvious suppression effect (P＜0.01), and the lung exponential quantity obviously reduces, and the lung tissue lesion degree obviously alleviates.
Table 1 medicine of the present invention is to the pulmonary inflammatory influence (x ± s of influenza virus infecting mouse; N=10)
Group lung exponential quantity suppression ratio (%)
Infect matched group 1.54 ± 0.18---
Normal control group 1.03 ± 0.12
▲ ▲---
Baicalin group 1.36 ± 0.15
▲13.83
Fibrauretin group 1.45 ± 0.15 8.9
Medicine 1.30 ± 0.10 of the present invention
▲ ▲17.26
Annotate: compare with the infection matched group
▲P＜0.05,
▲ ▲P＜0.01
4.2 influence to proliferation of influenza virus amount in the mouse lung
Table 2 medicine of the present invention is to the influence (x ± s of proliferation of influenza virus amount in the mouse lung; N=10)
Group positive rate (%) suppression ratio
Infect matched group 45.01 ± 6.82---
Baicalin group 37.27 ± 5.21 16.56
Fibrauretin group 38.13 ± 4.72 13.58
Medicine 34.81 ± 3.28 of the present invention
▲23.74
Annotate: compare with the infection matched group
▲P＜0.05
Table 2 is the result show, medicine of the present invention obviously has inhibitory action to proliferation of influenza virus amount in the mouse lung.Baicalin group, fibrauretin group compare no difference of science of statistics with the infection matched group.But this bright medicine group is compared with baicalin group, fibrauretin group, and there were significant differences.
Above-mentioned experimental result shows that medicine of the present invention has than significant inhibitory effect propagation and the caused pneumonia of influenza virus, and this effect is that Synergistic by baicalin and fibrauretin is produced.
The extracorporeal bacteria inhibitor test of test example 2, medicaments injection of the present invention
1 experiment material
1.1 strain
The test bacterial strain uses therefor is the clinical separation pathogenic bacterium that 2001-2003 collects from Sichuan area, and all strains are being collected isolating unit (Hospital Affiliated To Chengdu Traditional Chinese Medicine Univ clinical laboratory Bacteriology Room) all after identifying, adopts the API method to identify that again the back uses again.
1.2 be subjected to reagent
Medicaments injection of the present invention: press the method preparation of embodiment 6, yellowish-brown clear liquid, specification: 2ml/ prop up (every ml contains 5mg baicalin and 5mg fibrauretin).
Draw 20ml during test, after adding 50 ℃ of M-H agar culture medium mixings of 20ml thawing, sucking-off 20ml pastille culture medium is toppled over plate from 40ml, add 20ml in the remaining 20ml pastille culture medium again and do not have the dilution of medicine agar culture medium, behind the mixing again sucking-off 20ml topple over plate, the rest may be inferred, promptly with this doubling dilution prepare baicalin, fibrauretin content be 5,2.5,1.25 ... 0.0098mg/ml serial pastille plate stand-by.
The fibrauretin injection:
Xanchromatic clear liquid; The accurate word Z53020075 of traditional Chinese medicines; 2ml/ props up; Specification: 2ml: 20mg (every 1ml is equivalent to fibrauretin 10mg); Lot number: 030202; Produce by Yunnan China fir elm pharmaceutical Co. Ltd.
Draw 20ml during test, after adding 50 ℃ of M-H agar culture medium mixings of 20ml thawing, sucking-off 20ml pastille culture medium is toppled over plate from 40ml, add 20ml in the remaining 20ml pastille culture medium again and do not have the dilution of medicine agar culture medium, behind the mixing again sucking-off 20ml topple over plate, the rest may be inferred, promptly with this doubling dilution prepare fibrauretin content be 5,2.5,1.25 ... 0.0098mg/ml serial pastille plate stand-by.
Baicalin for injection liquid:
The brownish red clear liquid, self-control, specification: every ml contains baicalin 10mg.
Draw 20ml during test, after adding 50 ℃ of M-H agar culture medium mixings of 20ml thawing, sucking-off 20ml pastille culture medium is toppled over plate from 40ml, add 20ml in the remaining 20ml pastille culture medium again and do not have the dilution of medicine agar culture medium, behind the mixing again sucking-off 20ml topple over plate, the rest may be inferred, promptly with this doubling dilution prepare content of baicalin be 5,2.5,1.25 ... 0.0098mg/ml serial pastille plate stand-by.
1.3 culture medium
The M-H culture medium is produced by the extensive and profound in meaning star biotechnology in Beijing Co., Ltd.
The M-H broth bouillon: take by weighing 25g, add the 1000ml distilled water, the mixing packing is adjusted pH value to 7.2-7.4, and 121 ℃ of autoclavings 20 minutes are used to remove from office the drug sensitive test of the blue positive, negative aerobe.
The M-H solid medium: take by weighing 36.5g, add the 1000ml distilled water, the mixing packing is adjusted pH value to 7.2-7.4, and 121 ℃ of autoclavings 20 minutes are used to remove from office the drug sensitive test of the blue positive, negative aerobe.
2 test methods
2.1 the mensuration of minimal inhibitory concentration
Adopt the agar doubling dilution to measure the minimum inhibitory concentration (MIC) of medicaments injection of the present invention, fibrauretin injection, baicalin for injection liquid.In the agar plate surface that contains different pharmaceutical concentration, every some bacteria containing amount is about 10 with microbionation
5CFU/ml is hatched 18-24 hour observed result for 37 ℃, is the minimum inhibitory concentration (MIC value) of medicine to this bacterium with the least concentration of contained drug in the no bacterial growth plate culture medium.
2.2 the mensuration of minimum bactericidal concentration (MBC)
Adopt the liquid diluting method to measure the minimal bactericidal concentration (MBC) of medicaments injection of the present invention, fibrauretin injection, baicalin for injection liquid.After will being subjected to reagent liquid to carry out doubling dilution with M-H meat soup, (making final concentration is about 10 to be tried bacterium liquid respectively at inoculation 100ul in the 2ml pastille culture fluid
5CFU/ml), place 37 ℃ to hatch 18-20 hour, perusal is the minimum inhibitory concentration (MIC value) of medicine to this bacterium with the least concentration of contained drug in the no bacterial growth test tube.
The 0.01ml culture fluid that perusal is not had the test tube of bacterial growth is applied to the agar plate surface that does not contain medicine, continue 37 ℃ hatch 18-20 hour after, with the medicine least concentration in the corresponding test tube of not seeing bacterial growth on the agar plate as the minimum bactericidal concentration (MBC) of medicine to this bacterium.
3 results
Result of the test sees Table 3 and table 4, as seen from table, medicaments injection of the present invention to try leather Lan Shi positive bacteria, leather Lan Shi negative bacterium all has external antibacterial and bactericidal action in various degree, and its antibacterial activity is strong than fibrauretin injection, baicalin for injection liquid.
Table 3 respectively is subjected to the minimum inhibitory concentration (MIC) of reagent
| Strain | Medicaments injection of the present invention | The fibrauretin injection | Baicalin for injection liquid |
| (mg fibrauretin, baicalin/ml) | (the mg fibrauretin/ml) | (the mg baicalin/ml) | |
| Staphylococcus aureus | ????0.039 | ????0.625 | ????0.156 |
| Candida albicans | ????0.156 | ????0.313 | ????0.313 |
| The acid-resisting mycobacteria | ????0.078 | ????0.156 | ????0.625 |
| Shigella flexneri | ????2.5 | ????＞5 | ????＞5 |
| Escherichia coli | ????2.5 | ????＞5 | ????＞5 |
| Escherichia coli | ????1.25 | ????＞5 | ????2.5 |
| Salmonella | ????1.25 | ????＞5 | ????＞5 |
| Bacillus pyocyaneus | ????0.078 | ????＞5 | ????0.313 |
| Alpha streptococcus | ????0.02 | ????＞5 | ????0.078 |
| Group B streptococcus | ????0.02 | ????＞5 | ????0.156 |
| Diplococcus pneumoniae | ????0.02 | ????＞5 | ????0.156 |
| Micrococcus catarrhalis | ????0.078 | ????＞5 | ????0.156 |
| Gonococcus | ????0.02 | ????＞5 | ????0.078 |
The minimum inhibitory concentration of medicaments injection of the present invention is 0.059mg baicalin, fibrauretin/ml.
Table 4 respectively is subjected to the minimum bactericidal concentration (MBC) of reagent
| Strain | Medicaments injection of the present invention | The fibrauretin injection | Baicalin for injection liquid |
| (mg fibrauretin, baicalin/ml) | (the mg fibrauretin/ml) | (the mg baicalin/ml) | |
| Staphylococcus aureus | ????0.078 | ????0.625 | ????0.313 |
| Candida albicans | ????0.313 | ????0.625 | ????0.313 |
| The acid-resisting mycobacteria | ????0.156 | ????0.313 | ????1.25 |
| Shigella flexneri | ????＞5 | ????＞5 | ????＞5 |
| Escherichia coli | ????5.0 | ????＞5 | ????＞5 |
| Escherichia coli | ????2.5 | ????＞5 | ????2.5 |
| Salmonella | ????2.5 | ????＞5 | ????＞5 |
| Bacillus pyocyaneus | ????0.156 | ????＞5 | ????0.313 |
| Alpha streptococcus | ????0.078 | ????＞5 | ????0.078 |
| Group B streptococcus | ????0.039 | ????＞5 | ????0.156 |
| Diplococcus pneumoniae | ????0.039 | ????＞5 | ????0.156 |
| Micrococcus catarrhalis | ????0.156 | ????＞5 | ????0.313 |
| Gonococcus | ????0.078 | ????＞5 | ????0.156 |
More than the explanation of external bacteriostatic experiment, medicine of the present invention has been brought into play the effect of Synergistic with baicalin, fibrauretin combination, antibacterial activity uses fibrauretin or baicalin strong quite separately.
By above-mentioned test explanation, medicine of the present invention has been brought into play the effect of Synergistic in broad-spectrum antiseptic, antivirus test, than using the evident in efficacy of fibrauretin or baicalin arbitrarily separately.
The analgesic experiment of test example 3 medicaments injections of the present invention
1 experiment material
1.1 medicine
Medicaments injection of the present invention, the method preparation of pressing embodiment 6, specification: 2ml/ props up (every ml contains 5mg baicalin and 5mg fibrauretin).
The fibrauretin injection
Xanchromatic clear liquid; The accurate word Z53020075 of traditional Chinese medicines; 2ml/ props up; Specification: 2ml: 20mg (every 1ml is equivalent to fibrauretin 10mg); Lot number: 030202; Produce by Yunnan China fir elm pharmaceutical Co. Ltd.
Baicalin for injection liquid
The brownish red clear liquid, self-control, specification: every ml contains baicalin 10mg.
1.2 animal
Healthy white big ear rabbit in experiment a few days ago, is surveyed normal rectal temperature every day 4 times.Select fluctuation anus temperature every day to be no more than 0.2 ℃ 32 of animals, be divided into 4 groups at random, matched group, fibrauretin group, baicalin group and medicine of the present invention, 8 every group.
1.3 pyrogen
Typhoid fever, paratyphoid fever triple vaccine, the Ministry of Public Health institute of biological products produces, lot number: 99131-4.
2 experimental techniques
The basal body temperature of animal was surveyed earlier in test morning on the same day, gave tame rabbit ear vein injection pyrogenicity with typhoid fever, the paratyphoid fever triple vaccine of 0.5ml/kg, surveyed the anus temperature after half an hour respectively, and the corresponding medicine of intravenous injection or with the water of volume, 0.1ml/kg.Surveyed the anus temperature once in per 1 hour behind the medicine, totally 4 times, surveyed anus temperature and basic anus using warming therapy difference with different time, be the index of body temperature variation.
3 results
Table 5 medicaments injection of the present invention is to refrigeration function (x ± s of vaccine pyrogenicity rabbit; N=8)
Different time body temperature changing value behind the body temperature medicine after the group pyrogenicity (℃)
Raise (℃) 1h 2h 3h 4h
Matched group 1.07 ± 0.21 1.36 ± 0.14 1.46 ± 0.12 1.06 ± 0.23 0.55 ± 0.13
Baicalin group 1.07 ± 0.18 1.11 ± 0.17
▲ ▲0.88 ± 0.16
▲ ▲0.60 ± 0.34
▲0.36 ± 0.14
Fibrauretin group 1.06 ± 0.12 1.14 ± 0.15
▲ ▲0.96 ± 0.21
▲0.63 ± 0.45 0.40 ± 0.18
Medicine 1.07 of the present invention ± 0.16 1.12 ± 0.12
▲ ▲0.89 ± 0.13
▲ ▲0.60 ± 0.14
▲0.32 ± 0.16
▲
Annotate: compare with matched group
▲P＜0.05,
▲ ▲P＜0.01
As above shown in the table, medicine of the present invention causes that to vaccine the fervescence of rabbit has the obvious suppression effect, and uses baicalin or fibrauretin longer duration more separately, and medication still has after 4 hours and separates thermal effect.
The antiinflammatory test of test example 4 medicaments injections of the present invention
1 experiment material
1.1 medicine
Medicaments injection of the present invention (being subjected to reagent): press the method preparation of embodiment 6, yellowish-brown clear liquid, specification: 2ml/ prop up (every ml contains 5mg baicalin and 5mg fibrauretin).
The xanchromatic clear liquid of fibrauretin injection (contrast medicine); The accurate word Z53020075 of traditional Chinese medicines; 2ml/ props up; Specification: 2ml: 20mg (every 1ml is equivalent to fibrauretin 10mg); Lot number: 030202; Produce by Yunnan China fir elm pharmaceutical Co. Ltd.
Baicalin for injection liquid
The brownish red clear liquid, self-control, specification: every ml contains baicalin 10mg.
QINKAILING ZHUSHEYE
Pale brown color or brownish red clear liquid, the accurate word Z11020268 of traditional Chinese medicines, specification: 2ml/ prop up (every ml contains baicalin 5mg, total ammonia 2.5mg), lot number: 020801; Pharmaceutical Factory of Beijing University of Chinese Medicine produces.
Other medicines
Oleum Terebinthinae is Zixi, a Jiangxi pharmaceutical factory product, lot number: 020902.
1.2 animal and grouping
50 of Kunming kind healthy mices, male, body weight 20g ± 2g is provided by Chengdu University of Traditional Chinese Medicine zoopery center.Be divided into 5 groups at random, be respectively medicine of the present invention, fibrauretin group, baicalin group, QINGKAILING group and blank group, 10 every group.
50 of SD rats, male, body weight 200g ± 20g is provided by Chengdu University of Traditional Chinese Medicine zoopery center.To divide at random in order organizing, to be respectively medicine of the present invention, fibrauretin group, baicalin group, QINGKAILING group and blank group, 10 every group.
2 methods
2.1 mice auricle swelling method
Five groups are all adopted intraperitoneal injection, and wherein the blank group gives the distilled water with volume.0.1ml/10g, 1 time/day, continuous 7 days.After the last administration 1 hour, be coated with 100% dimethylbenzene on ear two sides, a mice left side, auris dextra is contrast, put to death mice after 4 hours, cut two ears, prepare the mice auricle with 6mm diameter card punch along the auricle baseline, claim weight in wet base with electronic scale, with the difference of two ear weight as swelling degree (inflammation index).
2.2 rat Oleum Terebinthinae air bag granulation hyperplasia method
Five groups of rats are all adopted intraperitoneal injection, and wherein the blank group gives the distilled water with volume.0.3ml/100g, 1 time/day, continuous 10 days.Prepare model in the time of administration, promptly under the shallow fiber crops of ether, to form air bag, in air bag, inject genuine turpentine oil 1ml then in the scapular region of back subcutaneous injection 20ml of every Mus air.Extract gas in the capsule after 24 hours out.1 hour execution rat after the last administration on the 10th, and peel off the wall internal granuloma, after the normal saline rinsing, put 80 ℃ of baking boxs bakings and claim dry weight after 6 hours.
3 date processing
Experimental data is represented with x ± s, checks than employing t between group.
4 results and analysis
In mice auricle swelling method, being tried the swelling of the inductive mice auricle of four medicine xylol all has inhibitory action, obvious with medicine of the present invention and the effect of QINGKAILING group, and the two is there was no significant difference relatively.In rat Oleum Terebinthinae air bag granulation hyperplasia method, medicine of the present invention and QINGKAILING group have inhibitory action to granulation hyperplasia, and baicalin group, fibrauretin group are to its not statistically significant that influences.See Table 6
Table 6 inductive mice ear of medicine xylol of the present invention and rat Oleum Terebinthinae air bag granulation hyperplasia
Influence
Grouping ear swelling degree (mg) granuloma dry weight (mg)
Blank group 10 ± 1.8 1.02 ± 0.33
Medicine 4.3 ± 1.5 of the present invention
▲ ▲0.52 ± 0.30
▲
Fibrauretin group 7.8 ± 1.6
▲0.91 ± 0.25
Baicalin group 7.5 ± 1.2
▲0.87 ± 0.24
QINGKAILING group 5.1 ± 1.3
▲ ▲0.48 ± 0.27
▲
Annotate: compare with the blank group
▲P＜0.05,
▲ ▲P＜0.01
The explanation of antiinflammatory result of experiment, the fibrauretin injection only has certain inhibitory action to acute inflammation; Medicine of the present invention all has good inhibitory effect to acute, subacute inflammation, compares no difference of science of statistics with the QINGKAILING group.(it is reported, show that by screening study QINKAILING ZHUSHEYE is to pulmonary's active chronic inflammation to the used medicine of sars period, to the medicine of lung index, inflammatory factor, the inflammatory exudation effect of having clear improvement (Zhang Dongfeng. how long anti-sars new drug research road has. Chinese medicine newspaper, 2003-6-11)), illustrate that medicine of the present invention has with the identical drug effect of QINKAILING ZHUSHEYE, to pulmonary's active chronic inflammation, to the effect of having clear improvement of lung index, inflammatory factor, inflammatory exudation.
Test example 5 medicines of the present invention are to the influence of rat immunity function
1 material
1.1 medicine
Medicaments injection of the present invention (being subjected to reagent): press the method preparation of embodiment 6, yellowish-brown clear liquid, specification: 2ml/ prop up (every ml contains 5mg baicalin and 5mg fibrauretin).
Fibrauretin injection (contrast medicine)
Xanchromatic clear liquid; The accurate word Z53020075 of traditional Chinese medicines; 2ml/ props up; Specification: 2ml: 20mg (every 1ml is equivalent to fibrauretin 10mg); Lot number: 030202; Produce by Yunnan China fir elm pharmaceutical Co. Ltd.
Baicalin for injection liquid
The brownish red clear liquid, self-control, specification: every ml contains baicalin 10mg.
Other medicines
Tetramethyl azo azoles indigo plant (MTT), the inferior maple of dimethyl are Fluka company product; RPMI-1640 is a GIBCO company product; Phytohaemagglutinin (PHA) is available from Sigma company.
1.2 animal
120 of mices are planted by Switzerland, and male and female have concurrently, and in 4 ages in week, body weight 18g～20g is provided by Chengdu University of Traditional Chinese Medicine zoopery center.
1.3 experiment grouping
40 mices are divided into 4 groups at random, blank group, medicine of the present invention, baicalin group and fibrauretin group, 10 every group.
2 detect index and method
2.1 the carbon clearance method is surveyed monokaryon-macrophage phagocytic function
Give injection relative medicine in the mouse peritoneal, 0.1ml/10g body weight, 1 time/day.The blank group waits the capacity sterile saline with method, continuous 7 days.Animal tail vein injection burnt black ink diluent 0.1ml10g after the last administration
-1Injection back 2min, 10min from eye socket posterior vein treating the preponderant disease instead of the secondary disease blood 20ul, are dissolved in 4ml0.1%Na respectively
2CO
3Shake up in the solution, measure absorbance with spectrophotometer under 680nm, calculate and clean up index K value, formula is:
K＝(lgOD
2-lgOD
10)/(t
10-t
2)
[K is for cleaning up index; OD
2, OD
10OD value during for 2min and 10min]
2.2 the mensuration of serum HD50 element
Give injection relative medicine in the mouse peritoneal, 0.1ml/10g body weight, 1 time/day.The blank group waits the capacity sterile saline with method, continuous 7 days.Carry out immunity at the 3rd day animal lumbar injection sheep red blood cell (SRBC) 0.5ml/ (2.5%), the last administration is extractd eyeball of mouse and is got blood 1ml after 1 hour, and separation of serum carries out hemolysin and measures and calculate half hemolysis value (HC
50).Formula is:
HC
50=(sample light absorption value/control tube half light absorption value) * extension rate value
2.3 the breeder reaction of mouse T lymphocyte
Give injection relative medicine in the mouse peritoneal, 0.1ml/10g body weight, 1 time/day.The blank group waits the capacity sterile saline with method, continuous 7 days.The last administration was put to death mice after 2 hours, and the aseptic spleen of getting is used the RPMI-1640 re-suspended cell, is prepared into 5 * 10
6Ml
-1Splenocyte suspension is inoculated in 96 well culture plates with every hole 100ul, and (final concentration is 30ugml to add PHA
-1), place 37 ℃ of 5% CO
2Cultivated 48 hours in the incubator, and finish preceding 4 hours every hole adding 5mgml in cultivating
-1MTT20ul collects splenocyte to be measured in the measuring tube after 4 hours, with 2200rmin
-1Centrifugal 5min, abandoning supernatant, every pipe adds the inferior maple 250ul of diformazan cell lysis, after cell fully dissolves, gets 100ul detects 570nm on microplate reader absorbance.
3 statistical procedures
Experimental data is represented with x ± s, checks than employing t between group.
4 results
4.1 influence to the mice non-specific immunity
Table 7 medicine of the present invention is to the influence of mouse monokaryon macrophage phagocytic function
Index (* 10 is cleaned up in grouping
3)
Blank group 4.82 ± 0.73
Fibrauretin group 10.21 ± 2.26
▲
Baicalin group 12.24 ± 1.96
▲
Medicine 16.56 ± 2.71 of the present invention
▲ ▲
Annotate: compare with the blank group
▲P＜0.05,
▲ ▲P＜0.001
To the exponential influence of carbon clearance, medicine of the present invention and blank group, fibrauretin group, baicalin group more all have significant difference (P＜0.001, P＜0.01) for each group medication; Fibrauretin group and blank group more variant (P＜0.05).Baicalin group and blank group more variant (P＜0.05).Be the phagocytic function that medicine of the present invention can significantly improve the mouse monokaryon macrophage, and brought into play the effect of Synergistic, drug effect is used separately with baicalin, fibrauretin and is compared, and effect is better.
4.2 influence to the mouse humoral immune function
The result shows that medicine of the present invention can significantly improve mice serum HD50 element, and imitates than the baicalin group, with blank group, fibrauretin group significant difference (P＜0.01) is arranged more all; Fibrauretin group and blank group be no significant difference (P＞0.05) relatively.See Table 8
The influence of table 8 pair mouse humoral immune function
The plain HC of grouping HD50
50
Blank group 32.24 ± 10.89
Fibrauretin group 40.01 ± 12.35
Baicalin group 43.28 ± 14.35
▲
Medicine 74.32 ± 12.57 of the present invention
▲ ▲ △
Annotate: compare with the blank group
▲P＜0.05,
▲ ▲Compare with the fibrauretin group P＜0.01
△P＜0.01
4.3 to the mouse cell Immune Effects
For the influence of mouse T lymphocyte absorbance, medicine of the present invention and blank group, fibrauretin group relatively have significant difference (P＜0.01); Fibrauretin group and baicalin group and blank group more variant (P＜0.05).As shown in table 9
Table 9 pair mouse cell Immune Effects
Grouping T lymphocyte absorbance
Blank group 0.81 ± 0.11
Fibrauretin group 1.24 ± 0.08
▲
Baicalin group 1.62 ± 0.13
▲
Medicine 3.57 ± 0.05 of the present invention
▲ ▲ △
Annotate: compare with the blank group
▲P＜0.05,
▲ ▲Compare with the fibrauretin group P＜0.01
△P＜0.01
5 brief summaries
Above-mentioned experiment is by measuring the influence of cleaning up index, HD50 element and T lymphocyte transformation function of medicaments injection of the present invention to mice, the immunoregulation effect of research medicaments injection of the present invention.Compare with the blank group, medicaments injection of the present invention can significantly strengthen phagocytic function, the raising body antibody horizontal of macrophage and promote lymhocyte transformation rate.Illustrate that medicaments injection of the present invention can significantly improve the nonspecific immunity and the specific immune function of body.With fibrauretin injection, baicalin for injection liquor ratio, the facilitation of medicaments injection pair cell of the present invention immunity and nonspecific immunity is more remarkable, and medicaments injection of the present invention has obvious facilitation to humoral immunization, and the fibrauretin injection is not found the effect of this respect.
The irritant experiment of test example 6 medicine eye drop of the present invention
1, experiment material:
1.1 animal: 5 of adult healthy rabbit;
1.2 medicine: the blank product of this study sample and sample.
2, experimental technique:
Directly splashed into eyes 2.1 will try thing, every eyes splash into 2;
2.2 administration and observation: during test this study sample is splashed in eyes conjunctival sac of rabbit, opposite side splashes into normal saline.Made eyes after the administration passive closed 5～10 seconds.The local response situation of 6,24,48,72 hours to 7 days eyes after the record administration.
3, the result judges and estimates:
By " eye stimulate reflection scoring " standard, every tame rabbit cornea is closed the score value addition of the stimulation reflection of conjunctiva, be the stimulation reflection total mark of a rabbit.The integration of each rabbit with divided by number of animals, be exactly the eye stimulation last score value of this rabbit to this medicine, by " eye irritation evaluation criterion ", judge that animal eye stimulates degree.
Table 10 pharmaceutical composition eye drop of the present invention and normal saline eye irritant reaction appraisal result
Group 6 hours 24 hours 48 hours 72 hours 7 days
Normal saline 00000
Fibrauretin baicalin eye drop 0.20 0.10 000
Result of the test: medicine of the present invention is non-stimulated substantially to eye.The safety of the eye drip preparation of proof medicine of the present invention.
The analgesic experiment of test example 7 medicinal tablets of the present invention
1 experiment material
1.1 medicine
Medicinal tablet of the present invention: by the preparation of embodiment 4 methods, specification: 0.25g (every contains 25mg baicalin and 25mg fibrauretin).
The accurate word (1995) of medicine is defended No. 002304 in fibrauretin sheet Yunnan, specification: 0.3g (every is equivalent to fibrauretin 100mg); Lot number: 030202; Produce by Yunnan Plant Pharmaceutical Industry Co., Ltd..
The accurate word H31022295 of baicalin sheet traditional Chinese medicines specification: 0.25g (every contains baicalin 100mg).Hehuang Pharmaceutical Co., Ltd., Shanghai produces.
Each two of above medicines are with 5%NAOH solution 20ml wiring solution-forming.
1.2 animal
Healthy white big ear rabbit in experiment a few days ago, is surveyed normal rectal temperature every day 4 times.Select fluctuation anus temperature every day to be no more than 0.2 ℃ 32 of animals, be divided into 4 groups at random, matched group, fibrauretin group, baicalin group and medicine of the present invention, 8 every group.
1.3 pyrogen
Typhoid fever, paratyphoid fever triple vaccine, the Ministry of Public Health institute of biological products produces, lot number: 99131-4.
2 experimental techniques
Fasting 1 day before the test, the basal body temperature of animal was surveyed in test morning on the same day earlier, gave tame rabbit ear vein injection pyrogenicity with typhoid fever, the paratyphoid fever triple vaccine of 0.5ml/kg, surveyed the anus temperature after half an hour respectively, irritated the corresponding medicine of stomach or with the water of volume, 5ml/kg.Surveyed the anus temperature once in per 1 hour behind the medicine, totally 4 times, surveyed anus temperature and basic anus using warming therapy difference with different time, be the index of body temperature variation.
3 results
Table 11 medicinal tablet of the present invention is to refrigeration function (x ± s of vaccine pyrogenicity rabbit; N=8)
The about back of body temperature different time body temperature changing value after the group pyrogenicity (℃)
Raise (℃) 1h 2h 3h 4h
Matched group 1.08 ± 0.13 1.35 ± 0.17 1.49 ± 0.14 1.08 ± 0.20 0.55 ± 0.13
Baicalin group 1.07 ± 0.16 1.29 ± 0.14 1.23 ± 0.16
▲0.60 ± 0.24
▲0.43 ± 0.12
Fibrauretin group 1.07 ± 0.15 1.29 ± 0.09 1.25 ± 0.12
▲0.73 ± 0.14 0.45 ± 0.13
Medicine 1.07 of the present invention ± 0.11 1.18 ± 0.12
▲ ▲1.14 ± 0.13
▲ ▲0.42 ± 0.14
▲ ▲0.32 ± 0.16
▲
Annotate: compare with matched group
▲P＜0.05,
▲ ▲P＜0.01
As above shown in the table, the tablet of pharmaceutical composition of the present invention causes that to vaccine the fervescence inhibitory action of rabbit is obvious.Irritate stomach relatively with baicalin sheet, fibrauretin sheet, advantage rapid-action, longer duration is arranged.Use by this description of test drug oral of the present invention and can bring into play the synergistic function that baicalin, fibrauretin share equally.
In sum, medicine of the present invention has than significant inhibitory effect propagation and the caused mice pneumonia thereof of influenza virus, to try leather Lan Shi positive bacteria, leather Lan Shi negative bacterium all has external antibacterial and bactericidal action in various degree, to typhoid fever, the paratyphoid fever triple vaccine causes that the fervescence of rabbit has the obvious suppression effect, and longer duration, medication still has after 4 hours and separates thermal effect, inductive mice ear of xylol and rat Oleum Terebinthinae air bag granulation hyperplasia significant inhibitory effect all arranged, illustrate that medicine of the present invention is to acute, subacute inflammation all has therapeutical effect, by measuring the clean up index of medicaments injection of the present invention to mice, the influence of HD50 element and T lymphocyte transformation function proves that medicine of the present invention can significantly improve nonspecific immunity and the specific immune function of mice.
And, by above pharmacodynamics test, fully prove baicalin and fibrauretin in the pharmaceutical composition of the present invention, though all be known chemical substance, but both compatibilities are used, be not the simple superposition of both effects, but have obvious role in synergism, for a person skilled in the art, not conspicuous.
The effect that pharmaceutical composition of the present invention has good broad-spectrum antiseptic, antiviral and improves immune function of human body provides a kind of new medication to select for clinical.
Claims (9)
1, a kind of pharmaceutical composition is characterized in that it is the preparation of being made by fibrauretin Fibrauretin, baicalin baicalin and pharmaceutically acceptable carrier.
2, pharmaceutical composition according to claim 1 is characterized in that the weight proportion of fibrauretin, baicalin is: 2.5～100 parts of fibrauretin, 5～100 parts of baicalins.
3, pharmaceutical composition according to claim 2 is characterized in that the weight proportion of fibrauretin, baicalin is: 5 parts of fibrauretin, 5 parts of baicalins.
4, according to the described pharmaceutical composition of claim 1～3, it is characterized in that fibrauretin Fibrauretin derives from menispermaceous plants Caulis Fibraureae Fibraurea recisa Pierre rattan and root, baicalin baicalin derives from the dry root of labiate Radix Scutellariae Scutellaria baicalensis Georgi.
5, pharmaceutical composition according to claim 1 is characterized in that described preparation is a solid preparation, liquid preparation.
6, pharmaceutical composition according to claim 5 is characterized in that described preparation is injection, capsule, tablet, micropill, eye drop, granule.
7, the purposes of the described pharmaceutical composition of claim 1 in preparation broad-spectrum antiviral, antimicrobial medicine.
8, the purposes of pharmaceutical composition according to claim 7 in analgesic, the antiphlogistic medicine of preparation.
9, the purposes of the described pharmaceutical composition of claim 1 in the medicine of preparation raising immune function of human body.
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| CN100434074C (en) * | 2005-08-29 | 2008-11-19 | 中国医学科学院皮肤病研究所 | Use of chloride 13-hexyl berberine and chloride 13-hexyl palmatine in preparation of medicine for treating skin mucosa herpes viral infection |
| CN1730034B (en) * | 2004-09-06 | 2010-07-21 | 成都百康医药工业药理毒理研究院 | Pharmaceutical composition for treating acute pneumonia, urinary tract infection and cholecystitis |
| CN102068473A (en) * | 2009-11-24 | 2011-05-25 | 时贞平 | Novel medicinal composition, preparation method, preparation and application thereof |
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| CN101797263B (en) * | 2007-01-11 | 2011-11-30 | 湖南九典制药有限公司 | Traditional Chinese medicine composite for antibiosis and antiphlogosis |
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| CN1239155C (en) * | 2003-01-23 | 2006-02-01 | 北京中医药大学 | Medicinal composition for treating ischemic cerebrovascular accident and preparation method |
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| CN1730034B (en) * | 2004-09-06 | 2010-07-21 | 成都百康医药工业药理毒理研究院 | Pharmaceutical composition for treating acute pneumonia, urinary tract infection and cholecystitis |
| CN100434074C (en) * | 2005-08-29 | 2008-11-19 | 中国医学科学院皮肤病研究所 | Use of chloride 13-hexyl berberine and chloride 13-hexyl palmatine in preparation of medicine for treating skin mucosa herpes viral infection |
| CN101007062B (en) * | 2005-12-31 | 2011-07-06 | 朱志宏 | Traditional Chinese medicine composition capable of resisting infection |
| CN101797263B (en) * | 2007-01-11 | 2011-11-30 | 湖南九典制药有限公司 | Traditional Chinese medicine composite for antibiosis and antiphlogosis |
| CN102068473A (en) * | 2009-11-24 | 2011-05-25 | 时贞平 | Novel medicinal composition, preparation method, preparation and application thereof |
| CN102068473B (en) * | 2009-11-24 | 2013-10-23 | 时贞平 | Medicinal composition, preparation method, preparation and application thereof |
| CN104606195A (en) * | 2015-01-26 | 2015-05-13 | 江西信尔诚动物药业有限公司 | Compound fibrauretin injection and preparation method thereof |
| CN104606195B (en) * | 2015-01-26 | 2017-01-04 | 江西信尔诚动物药业有限公司 | A kind of compound herba fibraureae recisea injection and preparation method thereof |
| CN115844913A (en) * | 2022-01-12 | 2023-03-28 | 南方医科大学皮肤病医院（广东省皮肤病医院、广东省皮肤性病防治中心、中国麻风防治研究中心） | Application of baicalin in preparation of medicine for treating gonococcal and/or drug-resistant gonococcal infection |
| CN115844913B (en) * | 2022-01-12 | 2023-11-07 | 南方医科大学皮肤病医院（广东省皮肤病医院、广东省皮肤性病防治中心、中国麻风防治研究中心） | Application of baicalin in preparation of medicines for treating gonococcus and/or drug-resistant gonococcus infection |
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