CN103272011A - Pharmaceutical composition for treating flu and preparation method of pharmaceutical composition - Google Patents

Pharmaceutical composition for treating flu and preparation method of pharmaceutical composition Download PDF

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CN103272011A
CN103272011A CN201310229899XA CN201310229899A CN103272011A CN 103272011 A CN103272011 A CN 103272011A CN 201310229899X A CN201310229899X A CN 201310229899XA CN 201310229899 A CN201310229899 A CN 201310229899A CN 103272011 A CN103272011 A CN 103272011A
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kidney
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杨勇
容蓉
李荣荣
丁嘉信
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杨勇
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Abstract

The invention relates to the technical field of traditional Chinese medicines, and in particular relates to a pharmaceutical composition for treating flu. The weight ratio of raw medicine materials including ephedra, asarum and radix aconiti praeparata is (1-3):(2-3):(5-7). The preparation method comprises the steps as follows: the raw medicine materials are mixed and then immersed in distilled water for 30 min; decoction is performed for two times by adding water with an amount of 8 times and 6 times of that of the raw medicine materials respectively, the decoction for the first time lasts for 30 min, and the decoction for the second time lasts for 20 min; filtering liquids are combined; and centrifugation is performed for 10 min at the speed of 3000 r/min, so that a solid dosage form or a liquid dosage form is prepared. The pharmaceutical composition which is prepared through the raw medicine materials with a specific proportion is used for treating external flu of crowds suffering from deficiency of kidney-yang, flu of crowds suffering from hypoimmunity and flu of crowds suffering from underlying diseases and the like. Experiments on animals show that the proportion of treatment effects is obviously larger than the proportion disclosed in the prior art, the death rate is reduced, the death protection rate is raised, the weight, the temperature and all visceral indexes are improved to a great extent, the usage amount of the raw medicine materials is small, the effect is good, the preparation method is simple, and the cost is low.

Description

A kind of pharmaceutical composition for the treatment of influenza and preparation method thereof
Technical field
The present invention relates to the Chinese medicine technical field, particularly a kind of pharmaceutical composition for the treatment of influenza also relates to described preparation of drug combination method.
Background technology
Influenza (Influenza) is called for short influenza, is a kind of acute suction tract disease with hyperinfection that is caused by influenza virus.It is that human health is threatened one of maximum infectious disease, has that infectiousness is strong, sickness rate is high, characteristics such as popular wide and mortality rate height, is the human pandemic infection disease that still can not effectively control so far.
The influenza clinical symptoms is heavier, and onset is hurried, and the complication rate height can cause death, and it is how sick or chronic basic patient's high-risk group arranged that the dead mostly is old and weak and childhood greatly.Mainly comprise: 1. age 65 years old; 2. have chronic pulmonary or cardiovascular system diseases adult and 6 months children's (comprising asthma); 3. renal dysfunction; 4. immunologic function suppresses (comprising medicine) person; 5. mid trimester of pregnancy above anemia of pregnant woman etc., still do not have specific drug treatment influenza so far.Influenza A H1N1 in 2009, ground accumulative total reports H1N1 influenza severe cases 4328 examples in China, dead 326 examples.In the severe cases, 32% case has chronic basic disease; In the death, 47% case has chronic basic disease.This shows that the chronic basic patient of weak and sickly, hypoimmunity is the high-risk group of all previous influenza always!
Doctor trained in Western medicine does not still have the specific treatment medicine at present, mainly takes anti symptom treatment etc.At present modern medicine at the control of influenza mainly with the development of antiviral drugs and specificity vaccine be applied as the master, but there are problems such as treatment limitation, drug resistance, untoward reaction in the Tamiflu that with the oseltamivir phosphate capsule is representative more, vaccine also just has defense reaction at the Virus Type of current popular, and the virus that morphs is not had preventive effect.Influenza vaccines were once thought a kind of proper prophylactic methods by modern medicine, but because the influenza virus variation is fast, outburst is rapid; Influenza vaccines developments and relatively lagging behind of using, even after the inoculation, reason such as the effective percentage of flu-prevention is low causes up to now, at high-risk group's preventing and controlling influenza, western medicine is good especially means and method never.
Influenza virus susceptible high-risk group's control is the difficult problem that modern medicine needs to be resolved hurrily always, and influenza that this crowd suffers from belongs to traditional Chinese medical science insufficiency of kidney-YANG exogenous disease more.Chinese medicine should disease advantage be determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs, " the whole synthesis adjusting " of the Chinese medicine compound multicomponent under organic conception instructs, multipath, many target spots." Ephedra asarum Radix Aconiti Lateralis Preparata soup " is to treat the classic prescriptions of simultaneous occurrence of syndromes in both YANG and YIN channels (being the insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor) very little on " Treatise on Febrile and Miscellaneous Disease ", formed by Herba Ephedrae, Herba Asari, gun additioner three flavor medicines, effect with dispelling cold by warming the meridian, strengthening vital QI to eliminate pathogenic factors, invigorating YANG and expelling the pathogenic factor in the superficies, clinical prolonged application and modern pharmacological research prove that all it is evident in efficacy.But the proportioning of disclosed three flavor medicines in the prior art, the inventor thinks it is not the best proportioning of effect.
Summary of the invention
Not the best problem of effect in order to solve the proportionings such as Ephedra asarum Radix Aconiti Lateralis Preparata soup that exist in the above prior art, the invention provides a kind of pharmaceutical composition of the treatment influenza that contains Herba Ephedrae, Herba Asari, Radix Aconiti Lateralis Preparata of better effects if.
The present invention also provides the preparation of drug combination method of described treatment influenza.
The present invention is achieved by the following measures:
A kind of pharmaceutical composition for the treatment of influenza, the crude drug weight proportion is as follows:
Herba Ephedrae: Herba Asari: Radix Aconiti Lateralis Preparata=1-3:2-3:5-7.
A kind of pharmaceutical composition for the treatment of influenza, the crude drug weight proportion is as follows:
Herba Ephedrae: Herba Asari: Radix Aconiti Lateralis Preparata=2:3:5.
A kind of pharmaceutical composition for the treatment of influenza, the crude drug weight proportion is as follows:
Herba Ephedrae: Herba Asari: Radix Aconiti Lateralis Preparata=3:2:7.
Described preparation of drug combination method, after crude drug mixed, distilled water immersion 30min added 8 times and 6 times of water gagings respectively and carries out twice decoction, one fries in shallow oil 30min, and two fry in shallow oil 20min, merging filtrate, 3000r/min, centrifugal 10min makes solid dosage forms or liquid dosage form.
Described preparation method, solid dosage forms are tablet, capsule, granule or pill.
Described preparation method, liquid dosage form are oral liquid, mixture, Emulsion, microemulsion or injection.
Beneficial effect of the present invention:
The pharmaceutical composition of the present invention that crude drug adopts specific proportioning to make; be used for the treatment of kidney yang deficiency syndrome crowd diseases caused by exogenous pathogenic factor; or hypoimmunity crowd's influenza or suffer from crowds' such as basic disease influenza; the result shows by zoopery; therapeutic effect is significantly better than disclosed proportioning in the prior art; mortality rate reduces; dead protective rate raises; body weight, body temperature, each organ index are had improvement significantly, are the medicines of effective treatment kidney yang deficiency syndrome influenza that a kind of crude drug consumption is few, effective, preparation method is simple, cost is low.
The specific embodiment
For a better understanding of the present invention, further specify below in conjunction with specific embodiment.
Embodiment 1:
Herba Ephedrae 1g, Herba Asari 2g, gun additioner 5g.
Embodiment 2:
Herba Ephedrae 2g, Herba Asari 3g, gun additioner 5g.
Embodiment 3:
Herba Ephedrae 3g, Herba Asari 2g, gun additioner 7g.
The comparative example 1:
Herba Ephedrae 6g, Herba Asari 3g, gun additioner 9g.
The comparative example 2:
Herba Ephedrae 6g, Herba Asari 3g, gun additioner 3g.
The comparative example 3:
Herba Ephedrae 6g, Herba Asari 6g, gun additioner 6g.
Above-mentioned 6 preparation of drug combination methods: after crude drug mixed according to proportioning, distilled water immersion 30min, add 8 times and 6 times of water gagings respectively and carry out twice decoction, one fries in shallow oil 30min, and two fry in shallow oil 20min, merging filtrate, 3000r/min, centrifugal 10min is concentrated into equal volume with medicinal liquid, and 4 ℃ of refrigerators are standby.
Effect test
One, the effect comparison test of existing medicine and proportioning raw materials
1, experiment material1.1 laboratory animal
KM mice 20 ± 2g, male, the SPF level provides (credit number: SCXK (Shandong) 20080002) by anti-zoopery center, Shandong, Shandong.Feeding environment: room temperature 22-26 ℃, relative humidity 40-70%RH.
1.2 experimental apparatus
Electro-heating standing-temperature cultivator, Shanghai Fuma Experiment Equipment Co., Ltd.'s (product type: DPX-9082B-1);
SW-CJ-1C type superclean bench (Purifying Equipment Co., Ltd., Suzhou);
MC-142L type electronic clinical thermometer (Dalian Omron (China) Co., Ltd.);
ZIL-2 type mice autonomic activities instrument (Beijing medical courses in general institute medicine grinds institute);
DT-880B hand-held infrared human body surface temperature quick sieving instrument (Hua Shengchang of Shenzhen machinery Industrial Co., Ltd.);
1.3 experiment reagent
The local strain in Mus pneumonopathy strain FM1 influenza virus A type (Influenza Virus A, Flu A) Beijing is drawn from Chinese CDC virosis institute;
Estradiol benzoate (the Ningbo second hormone factory, 120606) injection soybean oil (Zhejiang Tian Yushan medicinal oil company limited, lot number 120502);
Herba Ephedrae, gun additioner, Herba Asari (Jinan City builds connection Chinese medicine company limited prepared slices of Chinese crude drugs factory, 20110501) identify through TCD identification teaching and research room of Shandong Traditional Chinese Medicine University to meet standard under the Chinese Pharmacopoeia version continuous item in 2010;
The SPF Embryo Gallus domesticus is purchased in Domestic Fowls Inst., Shandong Academy of Agricultural Sciences.
, experimental technique
2.1 copying of insufficiency of kidney-YANG mouse model
With 80 of KM male mices, be divided into 10 of matched groups, 70 of modeling groups at random.Control group mice 20mLKg -1Lumbar injection 0.9% normal saline; Modeling group list of references method is also improved modeling dosage, 20mLKg -1Lumbar injection 0.4mgmL -1The estradiol benzoate diluent, every day 1 time, 15d copies the insufficiency of kidney-YANG model continuously, carries out index of correlation in modeling 12~13d and detects, by measuring autonomic activities, anus temperature, toe temperature, swimming time, with this decision model success or not.
2.2 " insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor " mouse model is set up
Be variable with the modeling group mice of copying success with body weight and anus temperature, be divided into 5 groups at random, be respectively insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group, the ribavirin matched group, embodiment 2 medicine groups, comparative example's 1 medicine group, comparative example's 2 medicine groups, comparative example's 3 medicine groups, influenza virus FM1 allantoic fluid (the blood clotting titre is 1:320) the collunarium infecting mouse of the high hemagglutinative titer that above-mentioned testing sieve is selected, the normal chick embryo allantoic liquid of 50 μ L of control group mice collunarium inoculation equivalent, before 0d is virus inoculation, 1d inoculates influenza virus, 2~5d is the pharmaceutical intervention treatment, recording the mice changes of body mass every day (weighs, survey body temperature), the mental status of observing mice, morbidity and death condition.
2.3 dosage design
The positive drug group, be subjected to the reagent group all to be equivalent to people's clinical equivalent dosage, infect the 2d administration, matched group, model group are with 10mLKg -1Volume gavage distilled water, all the other groups gavage the experimental group medicine with the ribavirin of volume and different proportionings, successive administration 5d irritates stomach every day 1 time.
2.4 observation index
(1) the anus temperature changes: measure the body temperature of inoculation influenza virus front and back mice, record variation tendency every day.
(2) changes of body mass: every day, the Weighing body quality was 1 time, continuously 7d.
(3) clinical symptoms: observe and respectively organize variations such as mice mental status, mobility, diet.
(4) death toll and mortality rate: mortality rate=dead animal number (only)/animal sum (only) * 100%, dead protective rate=[(model group death toll-administration group death toll)/model control group death toll] * 100%.
(5) organ index: experiment is plucked eyeball and is got blood (not adding anticoagulant heparin) after finishing, and 3500r/min is centrifugal, and 10min gets serum, and-70 ℃ of freezing preservations are standby.Get tissues such as respectively organizing mouse lung, spleen, thymus, take by weighing organ weights, calculate organ index.
2.5 statistical analysis
Adopt SPSS11.5 software, data with ± S represents, the relatively employing x of mortality rate 2Statistical procedures is carried out in check, relatively adopts one factor analysis of variance (one-way ANOVA) LSD check between group, and P<0.05 is for there being statistical significance.
Experimental result
3.1 the influence to the mouse model body weight
Though the control group mice body weight has reduction, recover gradually, the 5th~6d, body weight rises appreciably; From the inoculation influenza virus, though being the trend that continues to reduce, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice body weight do not see recovery up to 6d, modeling 2d rises with control group mice and compares, and significant difference (P<0.01) is arranged, this treated animal general performance depression, mortality rate height; Compare with insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group, though ribavirin group mice body weight is the trend of reduction, recover gradually, pharmaceutical intervention 3d rises, and significant difference (P<0.05) is arranged; Comparative example 2 and comparative example's 3 experimental mice body weight change are not obvious, all are reduction trend, and do not see obvious recovery; Comparative example's 1 experimental mice body weight just is reduction trend, and administration 2d rises and is ascendant trend (P<0.05) gradually; Embodiment 2 experimental mice body weight just are reduction trend, and administration 3d rises and is the trend that rises gradually, compares with insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group, and significance poor (P<0.05) is arranged; Wherein comparatively obvious with embodiment 2 experimental mice body weight gains.See Table 1.Annotate: compare with matched group, * P<0.01; Compare with model group, # P<0.05.
Table 1 is respectively organized mice body weight change contrast table
Figure 809319DEST_PATH_IMAGE002
3.2 the influence to mouse model body temperature
The 1st~6d control group mice anus temperature is organized mice apparently higher than other, and difference has statistical significance (P<0.01); The 1st~7d insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice anus temperature is significance and reduces (P<0.01), with the relatively body temperature significance reduction (P<0.05) of other drug treatment group; 3d rises, and experiment is respectively organized mice anus temperature and gone up in various degree, 7d and matched group comparison, anus temperature there was no significant difference (P〉0.05); The 1st~7d and matched group anus temperature compare, and insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group (P<0.01) has significant difference with embodiment 2 experimental grouies (P<0.01).See Table 2, annotate: compare * P<0.01 with matched group; Compare #P<0.05 with model group.Table 2 is respectively organized mouse temperature and is changed contrast table
Figure 515107DEST_PATH_IMAGE003
3.3 the influence to the mouse model mortality rate
Use influenza virus FM1 infecting mouse, matched group does not have death, and insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mortality rate 60% has higher mortality rate.Ribavirin group mortality rate 27.27%, dead protective rate 50.00%; Comparative example's 3 experimental group mortality rates 36.36%, dead protective rate 33.33%; Comparative example's 2 experimental group mortality rates 18.18%, dead protective rate 66.67%; Comparative example's 1 experimental group mortality rate 9.09%, dead protective rate 83.33%; Compare with insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group, the experimental group medicine all has the trend that reduces insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor mouse death rate in various degree, and wherein embodiment 2 experimental grouies do not have mortality rate.See Table 3.
The influence of table 3 pair death toll, mortality rate (
Figure 850274DEST_PATH_IMAGE004
± S, n=X)
Figure 392245DEST_PATH_IMAGE005
3.4 the influence to mouse model lung index
Experiment finishes the back and compares with control group mice, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse lung index obviously increases, difference has statistical significance (P<0.01), insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse lung index is apparently higher than other each medication therapy groups, difference has statistical significance (P<0.05), shows through treatment pulmonary infection degree obviously to improve.Wherein to improve effect best for the lungs index of embodiment 2 experimental grouies.See Table 4.
Table 4 and to the influence of lungs index (
Figure 471059DEST_PATH_IMAGE006
± S, n=X)
Annotate: compare * p<0.01 with matched group; Compare #p<0.05 with model group
3.5 the influence to the mouse model organ index
Spleen index: compare with matched group, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse spleen index reduces significantly, and significant difference (P<0.01) is arranged; Compare with insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse spleen index, ribavirin and each experimental mice spleen index obviously raise, and difference has statistical significance (P<0.05), and wherein embodiment 2 experimental grouies raise the most obvious.
Thymus index: compare with matched group, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse thymus index obviously reduces, significant difference (P<0.01) is arranged, and ribavirin group and comparative example's 2 experimental grouies, though thymus index raises to some extent than insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse thymus index, but be not increased to normal level as yet, still have significant difference (P<0.05) with control group mice, and other drug experimental group there was no significant difference (P〉0.05); Compare with insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group thymus index, except control group mice, comparative example's 1 experimental group and embodiment 2 experimental mice thymus indexs obviously raise, and significant difference (P<0.05) is arranged.
Renal index: compare with control group mice, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice renal index obviously reduces, significant difference (P<0.01) is arranged, except comparative example's 3 experimental grouies, though all the other each medication therapy groups mice renal indexs have rising in various degree but still have significant difference (P<0.01).
Testis index: compare with control group mice, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse testis index obviously reduces, significant difference (P<0.01) is arranged, raise though each medication therapy groups mouse testis index has in various degree, but still have significant difference (P<0.01); Compare with insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group, though ribavirin group and comparative example's 3 experimental mice testis index have certain amplitude to raise, but there was no significant difference (P〉0.05), all the other medication therapy groups mouse testis index rising amplitudes are comparatively obvious, and significant difference (P<0.05) is arranged.
The seminal vesicle index: compare with matched group, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice seminal vesicle index obviously reduces, and significant difference (P<0.01) is arranged; Compare with insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group, though ribavirin group and comparative example's 3 experimental mice seminal vesicle indexes have rising, but there was no significant difference (P〉0.05), all the other medication therapy groups seminal vesicle index rising amplitudes are comparatively obvious, and significant difference (P<0.05) is arranged.See Table 5.
Table 5 to the influence of other organ indexs ( ± S, n=X)
Annotate: compare * p<0.01 with matched group; Compare #p<0.05 with model group
4 brief summaries
It is the process of virus breeding amplification that virus goes down to posterity, comparatively responsive to the environment in the Embryo Gallus domesticus because of influenza virus, carries out in Embryo Gallus domesticus so virus goes down to posterity.And influenza virus can with the erythrocyte generation coagulation of animals such as people, chicken, principle is the receptor that influenza virus acts on erythrocyte surface, virus is adsorbed on the erythrocyte and produces coagulation, has special, sensitivity and advantages of simple operation, can be used as the index that virus is identified.And viral hemoagglutination is tired and can be reflected virus quantity and virulence thereof to a certain extent, utilize influenza virus to the characteristic of chicken red blood cell coagulation, by to the detection of the back virus of going down to posterity and to understand the virus multiplication degree with this logically be rational, that the method has is special, sensitivity and advantages of simple operation, can be used as the index that virus is identified.
This experimental result shows that the body temperature difference of model group and matched group has statistical significance, and body constitution is relatively weaker after the modeling of insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice, and its body temperature keeps lower state always behind the virus inoculation; The body weight of model group mice all reduces gradually, with matched group significant difference is arranged, and wherein body constitution is relatively poor after the modeling of insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice, resistance a little less than, become thin gradually and amplitude of variation bigger.Mortality rate is a kind of experimental index of the protective effect that is used to represent host susceptibility and medicine commute host usually of easy measuring and calculating, from integral level reaction virus virulence.Go out higher death condition behind the insufficiency of kidney-YANG model mice inoculation influenza virus, mortality rate height to 60%, and normal mouse is when the inoculation influenza virus, body constitution is good than the insufficiency of kidney-YANG model mice, resistance is also stronger relatively, only shows the anus relaxing the bowels with purgatives of warm nature and falls, and still is not enough to cause dead mouse.Mortality rate by insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model mice be 60% and the body temperature of diseases caused by exogenous pathogenic factor model mice descend and select the viral allantoic fluid that hemagglutinative titer is 1:320.
The main pathological basis of syndrome of deficiency of kidney-YANG is hypothalamus cells infringement and dysfunction, and functional and pathologic change also can appear in immune system, the metabolic mechanism of body simultaneously.Shorten reflection whole body function with the mice swimming time in this experiment early-stage Study and reduce, body temperature reduces the reflection aversion to cold and cold limbs, and indexs of correlation such as genitals's index are investigated the cold disease of libido, reflect the lethargy symptom with the autonomic activities number of times.Adopt the method for estradiol modeling comparatively ripe in the experiment, most lists of references have detected indexs of correlation such as gonadal hormone, the model group mice has tangible yang deficiency sign, show as that hair tarnish, tail are cold, asthenia, lethargy etc., comprehensive above index shows that employing lumbar injection estradiol benzoate causes mice insufficiency of kidney-YANG model, meets traditional Chinese medical science insufficiency of kidney-YANG disease sign preferably.
Influenza belongs to the traditional Chinese medical science " influenza " category, influenza infection can cause pulmonary edema, inflammatory exudation, hyperemia, thereby cause that pulmonary's weight increases, and the body weight of virus infected mice often reduces or do not increase, thereby cause the lung index to raise, the lung index is more big, and lung tissue pathology degree is more serious.Behind the FM1 infecting mouse, the anus temperature significance of mice reduces (P<0.01), and mortality rate obviously increases, and the lung index obviously increases.Compare with experiment in vitro, experiment can be from the effect of integral level reflection body disease-resistant poison in the animal body, thereby more near the antiviral state of human body, and therefore the easier attack hypoimmunity of infectious diseases such as influenza crowd studies the medicine with adjusting body's immunity and seem particularly important in the preventing and controlling influenza process.
The low mice of influenza virus collunarium infection immunity is adopted in this experiment, cause influenza virus pneumonia model, be evaluation index with mortality rate, anus temperature, lung index etc., the lung index obviously raises after the modeling, and compare research with ribavirin and different pharmaceutical experimental group, thus clear and definite its preventive and therapeutic effect to immunocompromised mice influenza, experimental result shows: matched group does not have death, the mortality rate of infection model group reaches 60%, illustrates that insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model is reliable; The mortality rate of different pharmaceutical experimental group is low than the infection model group all, different pharmaceutical experimental group therapeutic intervention is described after, the mice sign has in various degree to be improved, and can obviously improve the survival rate of model mice.Mice body weight behind the influenza virus infection, anus eliminating cold for resuscitation beginning descend, rise gradually behind the different pharmaceutical therapeutic intervention, the perusal lobe of the lung, serious viral pneumonia focus appears in insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group; pathological changes is involved 2 more than the lobe of the lung; lung tissue because of inflammatory exudation redness, consolidation takes place, and obviously reduces the lung index of mice after the pharmaceutical intervention, and experimental result has higher antiviral activity in conjunction with organ index and mortality rate explanation embodiment 2 experimental grouies.
Two, proportioning optimization Test again
Experimental technique is the same, and positive control drug increases " connect and spend pestilence Capsules group clearly ", and the result is as follows:
1.1 the influence to the mouse model body weight
The control group mice body weight is the trend that increases gradually; Insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice body weight is the trend that continues reduction, and the 4d body weight is down to minimum, does not see recovery yet up to the 6d body weight, compares with control group mice, and significant difference (P<0.01) is arranged; With insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice weight ratio, ribavirin group mice 1d body weight reduces, pharmaceutical intervention treatment back body weight increases gradually, 3d plays difference statistical significance (P<0.05); Connect and spend pestilence Capsules group mice clearly, the 1st~2d body weight is reduction trend, and the 3rd~6d body weight is the trend that increases gradually, and difference has statistical significance (P<0.05); Embodiment 1, embodiment 2 experimental mice 1d weight loss after infection rise subsequently gradually, and 3d plays difference statistical significance (P<0.05); Embodiment 3 experimental mice body weight continue to be the trend that rises gradually, and 2d rises, and difference has statistics meaning (P<0.05).See Table 6.
Table 6 pair mice body weight influences synopsis
Figure 511510DEST_PATH_IMAGE010
1.2 the influence to mouse model body temperature
The 0th~6d control group mice anus temperature is respectively organized mice apparently higher than other, and insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice anus temperature is reduction trend always, and difference has statistical significance (P<0.01); The 3rd~6d insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group body temperature is starkly lower than the other drug group, and difference has statistical significance (P<0.05); 3d rises, the ribavirin group, connect and to spend clearly pestilence Capsules group and each embodiment group mice anus temperature to go up in various degree, with matched group relatively, there was no significant difference (P〉0.05).See Table 7.
Table 7 pair mouse temperature influences synopsis
Figure 863994DEST_PATH_IMAGE011
1.3 the mouse model mortality rate is influenced
The influence of influenza infection mouse death rate, matched group do not have death condition and occur, and insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mortality rate 46.15% has higher mortality rate.Ribavirin group mortality rate 23.08%, dead protective rate 50.00%; Connect and spend pestilence Capsules group mortality rate 15.38% clearly, dead protective rate 66.67%; Embodiment 1 experimental group mortality rate 7.14%, dead protective rate 83.33%; Wherein embodiment 2,3 experimental grouies do not have the death condition appearance.See Table 8.
Table 8
Group N/ only Dosage/uL Dead protective rate/% Death toll/only Mortality rate/%
Matched group 10 50 \ 0 00
Model group 13 50 \ 6 46.15
The ribavirin group 13 50 50.00 3 23.08
Connect and spend pestilence capsule clearly 13 50 66.67 2 15.38
Embodiment 1 experimental group 14 50 83.33 1 7.14
Embodiment 2 experimental grouies 14 50 100 0 00
Embodiment 3 experimental grouies 14 50 100 0 00
1.4 the influence to mouse model lung index
Experiment finishes back model group mouse lung index and the apparent in view increase of control group mice, difference has statistical significance (P<0.01), after the pharmaceutical intervention, each organizes the mouse lung index and the model group mice relatively has reduction in various degree, difference has statistical significance (P<0.05), shows through treatment pulmonary infection degree obviously to improve.See Table 9.
Table 9
Figure 616662DEST_PATH_IMAGE013
Annotate: compare * p<0.05 with matched group; Compare #p<0.05 with model group
1.5 the influence to other organ indexs of mouse model
Spleen index: compare with control group mice, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse spleen index obviously reduces (P<0.01), each medicine group spleen index there was no significant difference (P〉0.05); Compare with insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse spleen index, connect and to spend clearly each medication therapy groups mouse spleen index of pestilence Capsules group and preferred side's various dose obviously raise (P<0.05), though ribavirin group mouse spleen index has rising to a certain degree, but be not increased to normal level as yet, compare with control group mice, difference has statistical significance (P<0.05).
Renal index: compare with control group mice, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice renal index obviously reduces, (P<0.01), though each medication therapy groups renal index raises to some extent than insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mice renal index, but be not increased to normal level as yet, and just still have significant difference (P<0.05) according to group mice renal index.
Thymus index: compare with matched group, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse thymus index obviously reduces, and significant difference (P<0.01) is arranged, and each medication therapy groups mouse thymus index has rising in various degree, compare with insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group, significant difference (P<0.05) is arranged.Except preferred side 2,3 groups, though having to raise in various degree, all the other each medication therapy groups mouse thymus indexes are not increased to normal level as yet.
Testis index: compare with matched group, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse testis index obviously reduces, significant difference (P<0.01) is arranged, still have significant difference (P<0.05) though each medication therapy groups mouse testis index has to raise in various degree with normal control group mouse thymus index; Compare with insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group, though even spending clearly, pestilence Capsules group mouse testis index has certain amplitude to raise, but there was no significant difference (P〉0.05) still, all the other medication therapy groups mouse testis index rising amplitudes are comparatively obvious, and significant difference (P<0.05) is arranged.
Seminal vesicle index: compare with matched group, insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group mouse testis index obviously reduces, significant difference (P<0.01) is arranged, raise though each medication therapy groups mice seminal vesicle index has in various degree, still have significant difference (P<0.05) with control group mice; With insufficiency of kidney-YANG diseases caused by exogenous pathogenic factor model group relatively, though each medication therapy groups mice seminal vesicle index has certain amplitude to raise, there was no significant difference (P〉0.05) still.See Table 10.
Each medicine group of table 10 to the influence of other organ indexs ( ± S, n=X)
Group Spleen index Thymus index Renal index The seminal vesicle index Testis index
Matched group 0.303±0.068# 0.230±0.065# 1.310±0.154# 0.334±0.071# 0.490±0.066#
Model group 0.198±0.055* 0.089±0.041* 0.989±0.211* 0.096±0.045* 0.208±0.076*
The ribavirin group 0.255±0.066 0.156±0.035*# 1.000±0.107* 0.167±0.049*# 0.296±0.089*#
Connect and spend pestilence capsule clearly 0.296±0.064# 0.180±0.047*# 1.021±0.083* 0.167±0.060*# 0.251±0.045*#
Embodiment 1 experimental group 0.291±0.049# 0.182±0.043*# 1.047±0.094* 0.198±0.027*# 0.270±0.033*#
Embodiment 2 experimental grouies 0.302±0.081# 0.196±0.040# 1.060±0.176* 0.205±0.058*# 0.274±0.073*#
Embodiment 3 experimental grouies 0.301±0.097# 0.198±0.044# 1.057±0.146* 0.200±0.028*# 0.286±0.039*#
Annotate: compare * p<0.01 with matched group; Compare #p<0.05 with model group.

Claims (6)

1. pharmaceutical composition for the treatment of influenza is characterized in that the crude drug weight proportion is as follows:
Herba Ephedrae: Herba Asari: gun additioner=1-3:2-3:5-7.
2. according to the pharmaceutical composition of claim 1, it is characterized in that the crude drug weight proportion is as follows:
Herba Ephedrae: Herba Asari: gun additioner=2:3:5.
3. according to the pharmaceutical composition of claim 1, it is characterized in that the crude drug weight proportion is as follows:
Herba Ephedrae: Herba Asari: gun additioner=3:2:7.
4. described preparation of drug combination method of claim 1, it is characterized in that after the crude drug mixing, distilled water immersion 30min, add 8 times and 6 times of water gagings respectively and carry out twice decoction, one fries in shallow oil 30min, and two fry in shallow oil 20min, merging filtrate, 3000r/min, centrifugal 10min makes solid dosage forms or liquid dosage form.
5. preparation method according to claim 4 is characterized in that solid dosage forms is tablet, capsule, granule or pill.
6. preparation method according to claim 4 is characterized in that liquid dosage form is oral liquid, mixture, Emulsion, microemulsion or injection.
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Publication number Priority date Publication date Assignee Title
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CN101683398A (en) * 2008-09-27 2010-03-31 李琪 Traditional Chinese medicine prescription for treating body continuous external infection chill
WO2011063553A1 (en) * 2009-11-27 2011-06-03 北京市卫生局临床药学研究所 Traditional chinese medicine for treating flu induced by flu virus including type a h1n1 virus
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