CN103655755B - Anti-influenza drug and preparation method thereof - Google Patents
Anti-influenza drug and preparation method thereof Download PDFInfo
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- CN103655755B CN103655755B CN201310580254.0A CN201310580254A CN103655755B CN 103655755 B CN103655755 B CN 103655755B CN 201310580254 A CN201310580254 A CN 201310580254A CN 103655755 B CN103655755 B CN 103655755B
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Abstract
<b> the present invention relates to flu medicine and preparation method thereof technical field, is a kind of anti-influenza drug and preparation method thereof; This anti-influenza drug raw materials by weight portion consists of Herba Achilleae 1 part to 3 parts, Radix Isatidis 1 part to 3 parts, Flos Trollii 1 part to 3 parts.Anti-influenza drug of the present invention is to the average IC of first, Influenza B virus
50be respectively 115.86 μ g/ml, 132.28 μ g/ml, average T I are 8.8,7.7; Anti-influenza drug 0.2g/kg dosage group of the present invention obviously can extend influenza a virus infection mouse survival natural law, reduces mortality rate; 0.1g/kg, 0.2g/kg dosage group can obviously suppress Lung Exponent value, and average inhibition is respectively 19.4%, 28.0%; Anti-influenza drug of the present invention has in certain body, the effect of In Vitro Anti influenza virus, provides pharmacology's foundation for it is used for the treatment of influenza.</b>
Description
Technical field
the present invention relates to flu medicine and preparation method thereof technical field, is a kind of anti-influenza drug and preparation method thereof.
Background technology
influenza (abbreviation influenza) is the Acute respiratory infectious disease caused by influenza virus (influenzavirus, IFV), can cause the multiple complications such as myocarditis, pneumonia, bronchitis.Be usually expressed as general malaise, feel cold, have a fever, and with upper respiratory tract infection symptoms such as headache, pharyngalgia, coughs.Have that sickness rate is high, onset rapidly, propagate fast, popular wide, variability is large, infectivity is strong and with features such as certain mortality rates.
influenza is the Acute respiratory infectious disease of a kind of harm humans health caused by influenza virus, often causes the seasonal whole world or some areas to be very popular." spanish influenza " of 1918 is very popular and causes the whole world dead more than 20,000,000 people.All can occur being very popular of an influenza between approximately every 10 years subsequently, its main cause is that influenza virus passes through hereditary variation fast, thus the identification of the human immune system that escaped, kills and remove.China is one of country of taking place frequently of influenza, and the health of influenza to people causes grave danger.The Chinese government always payes attention to the prevention and control of influenza, national influenza center has been set up in nineteen fifty-seven, within 1981, recover the international Influenza Surveillance net adding WHO, 31 provinces (municipality directly under the Central Government, autonomous region) in the whole nation have all carried out the monitoring of influenza at present.Since the end of the year 2003, Avian Influenza and Avian Influenza Virus Infection in Humans event occurred in Asia, the Chinese government has successively put into effect a series of policy, regulation, takes strong measure, uses the Method means of science, effectively controls the diffusion of bird flu and spread.
at present, Western medicine resisiting influenza virus has determined curative effect, acts on the features such as accurate, but every class medicine only works for certain action target spot of influenza virus, makes Western medicine be difficult to play desirable effect; And China's natural resources of Chinese medicinal materials enriches, research and use with a long history, meanwhile, Chinese medicine has the features such as flu-prevention occurs, many, the few side effects of action target spot.Chinese medicine prevention viral disease has following characteristic and advantage: 1. when treating viral infectious disease, traditional Chinese medical science Overall View and determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs thought are implemented wherein.Its pathological development can be analyzed on the one hand by the differentiation of syndromes in seasonal febrile diseases according to four phases: WEI,QI,YING and XUE systems theory of science of epidemic febrile disease of Chinese medicine; On the other hand can be theoretical by the determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs of the traditional Chinese medical science, recognize many set syndromic types, its Therapeutic Method just can with reference to traditional square medicine.Can effectively alleviate the infected's pathological lesion on the whole, not only emphasize eliminating evil but also pay attention to body self-regulation.Therefore, make full use of Chinese medicine resource, contribute to the difficult problem that we solve influenza infection.But Chinese medicine traditional decoction adopts traditional decoct mostly, its amount of water, to decoct the factor such as number of times, decocting time large on clinical efficacy impact, simultaneously Chinese medicine decoction also have taking dose large, carry the shortcomings such as inconvenient.Therefore, in order to meet modernization of industry of Chinese materia medica requirement, we need the TCM modern preparations developing applicable industrialization.
Summary of the invention
the invention provides a kind of anti-influenza drug and preparation method thereof, overcome the deficiency of above-mentioned prior art, it effectively can solve Western medicine and be difficult to play that desirable effect and Chinese medicine traditional decoction are large on clinical efficacy impact, taking dose is large and carry inconvenient problem.
one of technical scheme of the present invention is realized by following measures: a kind of anti-influenza drug, and raw materials by weight portion consists of Herba Achilleae 1 part to 3 parts, Radix Isatidis 1 part to 3 parts, Flos Trollii 1 part to 3 parts.
here is the further optimization and/or improvements to one of foregoing invention technical scheme:
above-mentioned anti-influenza drug obtains as follows, the first step, the Radix Isatidis powder of aequum is broken into Radix Isatidis coarse powder, the water soaking 24h to 48h of 6 times to 10 times Radix Isatidis coarse powder weight is added in Radix Isatidis coarse powder, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 DEG C to 110 DEG C, each reflux extracting time is 0.5h to 1.5h, filter after each reflux, extract, and obtain aqueous extract and medicinal residues, then the water adding 6 times to 10 times Radix Isatidis coarse powder weight in medicinal residues after filtration extracts next time, after reflux, extract, like this 2 times to 4 times, the aqueous extract at every turn obtained is combined and obtains water extraction mixed liquor, be the clear paste of 1.22 to 1.25 by the water extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C, then Radix Isatidis extract is obtained by after clear paste vacuum drying, the percent mass water content of Radix Isatidis extract is less than or equal to 6%,
second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtains mixing medical material, the ethanol water of mixing medical material 8 doubly to 12 times weight is added in mixing medical material, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 DEG C to 100 DEG C, each reflux extracting time is 1h to 3h, filter after each reflux, extract, and obtain alcohol extract and medicinal residues, then the ethanol water adding mixing medical material 8 doubly to 12 times weight in medicinal residues after filtration carries out reflux, extract, next time, after reflux, extract, like this 2 times to 4 times, the alcohol extract at every turn obtained is combined and obtains alcohol extraction mixed liquor, be the clear paste of 1.22 to 1.25 by the alcohol extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the percent mass water content of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
3rd step, after being mixed homogeneously by the mixed extract of Radix Isatidis extract and Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains anti-influenza drug.
in above-mentioned Radix Isatidis, the mass percentage of (R, S)-goitrin is 0.055% to 0.075%.
the mass percentage of above-mentioned Rupestonic Acid in Artemisia Rupestris L. Growing is 0.30% to 0.45%.
in the above-mentioned first step and second step, the pressure of concentrating under reduced pressure is 0.08Mpa, concentrating under reduced pressure temperature be 55 DEG C to 65 DEG C; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, and vacuum drying temperature is 55 DEG C to 65 DEG C; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with by No. three sieves be no more than 20% powder or/and, in second step, ethanol water to be concentration of volume percent be 60% to 80% ethanol water.
two of technical scheme of the present invention is realized by following measures: a kind of preparation method of anti-influenza drug, carry out in the steps below, the first step, the Radix Isatidis powder of aequum is broken into Radix Isatidis coarse powder, the water soaking 24h to 48h of 6 times to 10 times Radix Isatidis coarse powder weight is added in Radix Isatidis coarse powder, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 DEG C to 110 DEG C, each reflux extracting time is 0.5h to 1.5h, filter after each reflux, extract, and obtain aqueous extract and medicinal residues, then the water adding 6 times to 10 times Radix Isatidis coarse powder weight in medicinal residues after filtration extracts next time, after reflux, extract, like this 2 times to 4 times, the aqueous extract at every turn obtained is combined and obtains water extraction mixed liquor, be the clear paste of 1.22 to 1.25 by the water extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C, then Radix Isatidis extract is obtained by after clear paste vacuum drying, the percent mass water content of Radix Isatidis extract is less than or equal to 6%,
second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtains mixing medical material, the ethanol water of mixing medical material 8 doubly to 12 times weight is added in mixing medical material, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 DEG C to 100 DEG C, each reflux extracting time is 1h to 3h, filter after each reflux, extract, and obtain alcohol extract and medicinal residues, then the ethanol water adding mixing medical material 8 doubly to 12 times weight in medicinal residues after filtration carries out reflux, extract, next time, after reflux, extract, like this 2 times to 4 times, the alcohol extract at every turn obtained is combined and obtains alcohol extraction mixed liquor, be the clear paste of 1.22 to 1.25 by the alcohol extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the percent mass water content of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
3rd step, after being mixed homogeneously by the mixed extract of Radix Isatidis extract and Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains anti-influenza drug.
here is the further optimization and/or improvements to foregoing invention technical scheme two:
in above-mentioned Radix Isatidis, the mass percentage of (R, S)-goitrin is 0.055% to 0.075%.
the mass percentage of above-mentioned Rupestonic Acid in Artemisia Rupestris L. Growing is 0.30% to 0.45%.
in the above-mentioned first step and second step, the pressure of concentrating under reduced pressure is 0.08Mpa, and the temperature of concentrating under reduced pressure is 55 DEG C to 65 DEG C; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, and vacuum drying temperature is 55 DEG C to 65 DEG C; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with by No. three sieves be no more than 20% powder or/and, in second step, ethanol water to be concentration of volume percent be 60% to 80% ethanol water.
the average IC50 of anti-influenza drug of the present invention to first, Influenza B virus is respectively 115.86 μ g/ml, 132.28 μ g/ml, average T I are 8.8,7.7; Anti-influenza drug 0.2g/kg dosage group of the present invention obviously can extend influenza a virus infection mouse survival natural law, reduces mortality rate; 0.1g/kg, 0.2g/kg dosage group can obviously suppress Lung Exponent value, and average inhibition is respectively 19.4%, 28.0%; Anti-influenza drug of the present invention has in certain body, the effect of In Vitro Anti influenza virus, provides pharmacology's foundation for it is used for the treatment of influenza.
Detailed description of the invention
the present invention by the restriction of following embodiment, can not determine concrete embodiment according to technical scheme of the present invention and practical situation.
embodiment 1, this anti-influenza drug, raw materials by weight portion consists of Herba Achilleae 1 part to 3 parts, Radix Isatidis 1 part to 3 parts, Flos Trollii 1 part to 3 parts.
embodiment 2, this anti-influenza drug, raw materials by weight portion consists of Herba Achilleae 1 part or 3 parts, Radix Isatidis 1 part or 3 parts, Flos Trollii 1 part or 3 parts.
embodiment 3, this anti-influenza drug obtains by following preparation method, the first step, the Radix Isatidis powder of aequum is broken into Radix Isatidis coarse powder, the water soaking 24h to 48h of 6 times to 10 times Radix Isatidis coarse powder weight is added in Radix Isatidis coarse powder, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 DEG C to 110 DEG C, each reflux extracting time is 0.5h to 1.5h, filter after each reflux, extract, and obtain aqueous extract and medicinal residues, then the water adding 6 times to 10 times Radix Isatidis coarse powder weight in medicinal residues after filtration extracts next time, after reflux, extract, like this 2 times to 4 times, the aqueous extract at every turn obtained is combined and obtains water extraction mixed liquor, be the clear paste of 1.22 to 1.25 by the water extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C, then Radix Isatidis extract is obtained by after clear paste vacuum drying, the percent mass water content of Radix Isatidis extract is less than or equal to 6%,
second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtains mixing medical material, the ethanol water of mixing medical material 8 doubly to 12 times weight is added in mixing medical material, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 DEG C to 100 DEG C, each reflux extracting time is 1h to 3h, filter after each reflux, extract, and obtain alcohol extract and medicinal residues, then the ethanol water adding mixing medical material 8 doubly to 12 times weight in medicinal residues after filtration carries out reflux, extract, next time, after reflux, extract, like this 2 times to 4 times, the alcohol extract at every turn obtained is combined and obtains alcohol extraction mixed liquor, be the clear paste of 1.22 to 1.25 by the alcohol extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the percent mass water content of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
3rd step, after being mixed homogeneously by the mixed extract of Radix Isatidis extract and Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains anti-influenza drug.
embodiment 4, this anti-influenza drug obtains by following preparation method, the first step, the Radix Isatidis powder of aequum is broken into Radix Isatidis coarse powder, water soaking 24h or 48h of 6 times or 10 times Radix Isatidis coarse powder weight is added in Radix Isatidis coarse powder, reflux, extract, 2 times or 4 times, the temperature of each reflux, extract, is 80 DEG C or 110 DEG C, each reflux extracting time is 0.5h or 1.5h, filter after each reflux, extract, and obtain aqueous extract and medicinal residues, then the water adding 6 times or 10 times Radix Isatidis coarse powder weight in medicinal residues after filtration extracts next time, after reflux, extract, like this 2 times or 4 times, the aqueous extract at every turn obtained is combined and obtains water extraction mixed liquor, by the clear paste that the water extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C is 1.22 or 1.25, then Radix Isatidis extract is obtained by after clear paste vacuum drying, the percent mass water content of Radix Isatidis extract is less than or equal to 6%,
second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtains mixing medical material, the ethanol water of mixing medical material 8 times or 12 times weight is added in mixing medical material, reflux, extract, 2 times or 4 times, the temperature of each reflux, extract, is 80 DEG C or 100 DEG C, each reflux extracting time is 1h or 3h, filter after each reflux, extract, and obtain alcohol extract and medicinal residues, then the ethanol water adding mixing medical material 8 times or 12 times weight in medicinal residues after filtration carries out reflux, extract, next time, after reflux, extract, like this 2 times or 4 times, the alcohol extract at every turn obtained is combined and obtains alcohol extraction mixed liquor, by the clear paste that the alcohol extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C is 1.22 or 1.25, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the percent mass water content of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
3rd step, after being mixed homogeneously by the mixed extract of Radix Isatidis extract and Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains anti-influenza drug.
embodiment 5, as the optimization of above-described embodiment, in the Radix Isatidis of embodiment 5, the mass percentage of (R, S)-goitrin is 0.055% to 0.075%.
embodiment 6, as the optimization of above-described embodiment, the mass percentage of the Rupestonic Acid in Artemisia Rupestris L. Growing of embodiment 6 is 0.30% to 0.45%.
embodiment 7, as the optimization of above-described embodiment, in the first step of embodiment 7 and second step, the pressure of concentrating under reduced pressure is 0.08Mpa, and the temperature of concentrating under reduced pressure is 55 DEG C to 65 DEG C; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, and vacuum drying temperature is 55 DEG C to 65 DEG C; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with by No. three sieves be no more than 20% powder or/and, in second step, ethanol water to be concentration of volume percent be 60% to 80% ethanol water.
the pharmacodynamic experiment of the anti-influenza drug obtained according to the above embodiment of the present invention is as follows:
1, the anti-influenza drug that obtains of the above embodiment of the present invention is to the toxicity of mdck cell
anti-influenza drug the above embodiment of the present invention obtained and existing public anti-influenza drug ribavirin dilute by maintenance medium respectively, by the maintenance medium adding 2ml, 4ml, 8ml, 16ml, 32ml, 64ml and 128ml in every μ g respectively, be configured to 1:2,1:4,1:8,1:16,1:32,1:64 and 1:128 totally seven concentration respectively, be added to inoculation mdck cell and grown up in 96 well culture plates of monolayer, 100 μ l/ holes, the multiple hole of every dilution factor 4, establishes cell controls simultaneously.Culture plate is put 37
o
c, 5%CO
2
cultivate in incubator, every day, observation of cell growing state, determined that cell does not occur that the minimum extension rate of obvious regression is maximal non-toxic concentration (TC
0
), and calculate 50% toxic concentration (TC by Reed-Muench method
50
).
result, it is slow that the toxic action of the anti-influenza drug that the above embodiment of the present invention obtains to mdck cell shows as cell proliferation, granule is more, morphologic change, part cell breakage come off, the toxic action of mdck cell is alleviated along with the reduction of drug level, illustrate the anti-influenza drug that the above embodiment of the present invention obtains and ribavirin effective equally to mdck cell; To the average T C of MDCK cultured cell
0
with average TC
50
in table 1.
the anti-influenza drug that test example 2, the above embodiment of the present invention obtain is on the impact of pathological changes caused by virus (CPE)
get and inoculate mdck cell and the culture plate growing up to monolayer, inhale and abandon culture fluid, inoculate the tissue culture infective dose (100TCID of 100 times respectively
50
) different virus liquid 50 μ l, put 37
o
c, 5%CO
2
adsorb in incubator after 1 hour, inhale and abandon virus liquid, use Eagle
,
s maintenance medium washes cell surface 2 times, if cell controls group, virus control group, ribavirin variable concentrations (get TC
0
and following three 4 times of dilution factors totally four concentration), the anti-influenza drug variable concentrations that obtains of the above embodiment of the present invention (gets TC
0
and following three 2 times of dilution factors totally four concentration) administration group, 4 holes/group; Administration group adds different dilution medicinal liquid, and matched group adds maintenance medium, 100 μ l/ holes.Culture plate puts 37
o
c, 5%CO
2
cultivate in incubator, observation of cell pathological changes situation under every day inverted microscope, the record experimental result when virus control group cytopathy reaches 4 grades.Cytopathy judges by six grade standards, and presses Reed-Muench method calculating IC
50
, TI=TC
50
/ IC
50
.
–: Growth of Cells is normal, occurs without pathological changes;
±: cytopathy is less than 10% of whole cell monolayer;
1: cytopathy accounts for less than 25% of whole cell monolayer;
2: cytopathy accounts for less than 50% of whole cell monolayer;
3: cytopathy accounts for less than 75% of whole cell monolayer;
4: cytopathy accounts for more than 75% of whole cell monolayer.
the anti-influenza drug that the above embodiment of the present invention obtains has obvious inhibitory action to first, Influenza B virus, its average IC
50
be respectively 115.86 μ g/ml, 132.28 μ g/ml, average T I is respectively 8.8,7.7; The anti-influenza drug that the above embodiment of the present invention obtains and ribavirin are shown in Table 2 the impact that virus causes mdck cell pathological changes; The anti-influenza drug that the above embodiment of the present invention obtains and ribavirin the results are shown in Table shown in 3 antiviral study in vitro.
the anti-influenza drug that test example 3, the above embodiment of the present invention obtain is on the impact of infecting mouse mortality rate and life span
healthy kunming mice is divided into 6 groups at random by sex body weight, i.e. anti-influenza drug three dosed administration groups of obtaining of model control group, ribavirin group, antiviral granule group, the above embodiment of the present invention, often organize 12, the continuous gastric infusion of each administration group 10 days, once-a-day, matched group is to distilled water, and 2h after administration on the 3rd, except Normal group, all the other respectively organize mice respectively with 10LD
50
virus liquid collunarium infect, observe animal incidence record death toll day by day, within the 14th day after infection, calculate Death prevention rate and increase in life span.
death prevention rate (%)=(model group mortality rate-experimental group mortality rate)/model group mortality rate × 100%
increase in life span (%)=(experimental group the average survival time day-model group the average survival time day)/model group the average survival time day × 100%
as a result, the mortality rate of model control group is 83.3%, and the success of influenza Establishment of mouse model is described; The average mortality of the anti-influenza drug 0.1g/kg that the above embodiment of the present invention obtains, 0.2g/kg dosage group is 41.7 and 33.3 respectively; there is significant difference (P<0.01) compared with model control group; the protective effect of the anti-influenza drug influenza virus infected that the above embodiment of the present invention obtains and the effect of positive control drug antiviral granule are suitable, on the impact of infecting mouse mortality rate in table 4.
mean survival time obvious shortening compared with matched group of model control group, there is significant difference (P<0.01), the anti-influenza drug 0.2g/kg dosage group mean survival time that the above embodiment of the present invention obtains is 12.00 ± 2.66, obviously extend compared with model control group and have notable difference (P<0.01), its effect is better than antiviral granule; The anti-influenza drug 0.05g/kg that the above embodiment of the present invention obtains, 0.1g/kg dosage group mean survival time also obviously extend compared with model control group, be respectively 9.25 ± 3.11 and 10.33 ± 3.55, but compared with model control group there was no significant difference; On the impact of infecting mouse life span in table 5.
the anti-influenza drug that test example 4, the above embodiment of the present invention obtain is on the impact of Lung Index of mice infected by Influenza virus
healthy kunming mice is divided into 6 groups at random by sex body weight, i.e. anti-influenza drug three dosed administration groups of obtaining of Normal group, model control group, antiviral granule group, the above embodiment of the present invention, often organize 12, the continuous gastric infusion of each administration group 9 days, once-a-day, matched group to distilled water, 2h after administration on the 3rd, except Normal group, each group mice all under ether light anesthesia respectively with 15LD
50
virus liquid 50ul collunarium infect, Normal group is with method collunarium normal saline 50ul.24h after last administration, it is lethal to pluck eyeball blood-letting after each group mouse weights, takes out full lung after mice being soaked in 75% ethanol on aseptic operating platform, with brine twice, blot surperficial moisture content with filter paper, claim lung weight, observe the lungs change of animal, calculate Lung Exponent and lung suppression ratio.
lung Exponent=lung weight/body weight × 100
lung index=(the average Lung Exponent of the average Lung Exponent-experimental group of model control group) average Lung Exponent × 100 of/model control group
result, model control group has significant difference (P<0.01) compared with Normal group, Lung Exponent and the lung suppression ratio of the anti-influenza drug 0.2g/kg dosage group that the above embodiment of the present invention obtains are respectively 1.34 ± 0.44 and 28.0%, have significant difference (P<0.01) compared with model control group, its effect is suitable with antiviral granule; Lung Exponent and the lung suppression ratio of the anti-influenza drug 0.1g/kg dosage group that the above embodiment of the present invention obtains are respectively 1.50 ± 0.41 and 19.4%, there is notable difference (P<0.05) compared with model control group, and the anti-influenza drug 0.05g/kg dosage group Lung Exponent that the above embodiment of the present invention obtains also obviously reduces compared with model control group, but without significant difference; On the impact of Lung Index of mice infected by Influenza virus in table 6.
the average IC50 of anti-influenza drug of the present invention to first, Influenza B virus is respectively 115.86 μ g/ml, 132.28 μ g/ml, and average T I is respectively 8.8,7.7; Anti-influenza drug 0.2g/kg dosage group of the present invention obviously can extend influenza a virus infection mouse survival natural law, reduces mortality rate; Anti-influenza drug 0.1g/kg of the present invention, 0.2g/kg dosage group can obviously suppress Lung Exponent value, and suppression ratio is respectively 19.4%, 28.0%.Known by the result of study of pharmacodynamic experiment, anti-influenza drug of the present invention has in certain body, the effect of In Vitro Anti influenza virus, in its body, resisiting influenza virus effect is better than antiviral granule, provides pharmacology's foundation for it is used for the treatment of influenza.
above technical characteristic constitutes embodiments of the invention, and it has stronger adaptability and implementation result, can increase and decrease non-essential technical characteristic according to actual needs, meet the demand of different situations.
Claims (10)
1. an anti-influenza drug, is characterized in that raw materials by weight portion consists of Herba Achilleae 1 part to 3 parts, Radix Isatidis 1 part to 3 parts, Flos Trollii 1 part to 3 parts, wherein: this anti-influenza drug obtains as follows, the first step, the Radix Isatidis powder of aequum is broken into Radix Isatidis coarse powder, the water soaking 24h to 48h of 6 times to 10 times Radix Isatidis coarse powder weight is added in Radix Isatidis coarse powder, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 DEG C to 110 DEG C, each reflux extracting time is 0.5h to 1.5h, filter after each reflux, extract, and obtain aqueous extract and medicinal residues, then the water adding 6 times to 10 times Radix Isatidis coarse powder weight in medicinal residues after filtration extracts next time, after reflux, extract, like this 2 times to 4 times, the aqueous extract at every turn obtained is combined and obtains water extraction mixed liquor, be the clear paste of 1.22 to 1.25 by the water extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C, then Radix Isatidis extract is obtained by after clear paste vacuum drying, the percent mass water content of Radix Isatidis extract is less than or equal to 6%,
Second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtains mixing medical material, the ethanol water of mixing medical material 8 doubly to 12 times weight is added in mixing medical material, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 DEG C to 100 DEG C, each reflux extracting time is 1h to 3h, filter after each reflux, extract, and obtain alcohol extract and medicinal residues, then the ethanol water adding mixing medical material 8 doubly to 12 times weight in medicinal residues after filtration carries out reflux, extract, next time, after reflux, extract, like this 2 times to 4 times, the alcohol extract at every turn obtained is combined and obtains alcohol extraction mixed liquor, be the clear paste of 1.22 to 1.25 by the alcohol extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the percent mass water content of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
3rd step, after being mixed homogeneously by the mixed extract of Radix Isatidis extract and Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains anti-influenza drug.
2. anti-influenza drug according to claim 1, is characterized in that the mass percentage of (R, S) in Radix Isatidis-goitrin is 0.055% to 0.075%.
3. anti-influenza drug according to claim 1 and 2, is characterized in that the mass percentage of Rupestonic Acid in Artemisia Rupestris L. Growing is 0.30% to 0.45%.
4. anti-influenza drug according to claim 1 and 2, is characterized in that in the first step and second step, and the pressure of concentrating under reduced pressure is 0.08Mpa, and the temperature of concentrating under reduced pressure is 55 DEG C to 65 DEG C; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, and vacuum drying temperature is 55 DEG C to 65 DEG C; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with the powder being no more than 20% by No. three sieves; Or/and, in second step, ethanol water to be concentration of volume percent be 60% to 80% ethanol water.
5. anti-influenza drug according to claim 3, is characterized in that in the first step and second step, and the pressure of concentrating under reduced pressure is 0.08Mpa, and the temperature of concentrating under reduced pressure is 55 DEG C to 65 DEG C; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, and vacuum drying temperature is 55 DEG C to 65 DEG C; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with the powder being no more than 20% by No. three sieves; Or/and, in second step, ethanol water to be concentration of volume percent be 60% to 80% ethanol water.
6. the preparation method of an anti-influenza drug according to claim 1, it is characterized in that carrying out in the steps below, the first step, the Radix Isatidis powder of aequum is broken into Radix Isatidis coarse powder, the water soaking 24h to 48h of 6 times to 10 times Radix Isatidis coarse powder weight is added in Radix Isatidis coarse powder, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 DEG C to 110 DEG C, each reflux extracting time is 0.5h to 1.5h, filter after each reflux, extract, and obtain aqueous extract and medicinal residues, then the water adding 6 times to 10 times Radix Isatidis coarse powder weight in medicinal residues after filtration extracts next time, after reflux, extract, like this 2 times to 4 times, the aqueous extract at every turn obtained is combined and obtains water extraction mixed liquor, be the clear paste of 1.22 to 1.25 by the water extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C, then Radix Isatidis extract is obtained by after clear paste vacuum drying, the percent mass water content of Radix Isatidis extract is less than or equal to 6%,
Second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtains mixing medical material, the ethanol water of mixing medical material 8 doubly to 12 times weight is added in mixing medical material, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 DEG C to 100 DEG C, each reflux extracting time is 1h to 3h, filter after each reflux, extract, and obtain alcohol extract and medicinal residues, then the ethanol water adding mixing medical material 8 doubly to 12 times weight in medicinal residues after filtration carries out reflux, extract, next time, after reflux, extract, like this 2 times to 4 times, the alcohol extract at every turn obtained is combined and obtains alcohol extraction mixed liquor, be the clear paste of 1.22 to 1.25 by the alcohol extraction mixed liquor concentrating under reduced pressure density obtained at temperature is 60 DEG C, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the percent mass water content of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
3rd step, after being mixed homogeneously by the mixed extract of Radix Isatidis extract and Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains anti-influenza drug.
7. the preparation method of anti-influenza drug according to claim 6, is characterized in that the mass percentage of (R, S) in Radix Isatidis-goitrin is 0.055% to 0.075%.
8. the preparation method of the anti-influenza drug according to claim 6 or 7, is characterized in that the mass percentage of Rupestonic Acid in Artemisia Rupestris L. Growing is 0.30% to 0.45%.
9. the preparation method of the anti-influenza drug according to claim 6 or 7, is characterized in that in the first step and second step, and the pressure of concentrating under reduced pressure is 0.08Mpa, and the temperature of concentrating under reduced pressure is 55 DEG C to 65 DEG C; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, and vacuum drying temperature is 55 DEG C to 65 DEG C; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with the powder being no more than 20% by No. three sieves; Or/and, in second step, ethanol water to be concentration of volume percent be 60% to 80% ethanol water.
10. the preparation method of anti-influenza drug according to claim 8, is characterized in that in the first step and second step, and the pressure of concentrating under reduced pressure is 0.08Mpa, and the temperature of concentrating under reduced pressure is 55 DEG C to 65 DEG C; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, and vacuum drying temperature is 55 DEG C to 65 DEG C; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with the powder being no more than 20% by No. three sieves; Or/and, in second step, ethanol water to be concentration of volume percent be 60% to 80% ethanol water.
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