CN103655755A - Anti-influenza drug and preparation method thereof - Google Patents
Anti-influenza drug and preparation method thereof Download PDFInfo
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- CN103655755A CN103655755A CN201310580254.0A CN201310580254A CN103655755A CN 103655755 A CN103655755 A CN 103655755A CN 201310580254 A CN201310580254 A CN 201310580254A CN 103655755 A CN103655755 A CN 103655755A
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- 206010022000 influenza Diseases 0.000 title claims abstract description 81
- 239000003814 drug Substances 0.000 title claims abstract description 79
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 229940079593 drug Drugs 0.000 title abstract description 11
- 235000015784 Artemisia rupestris Nutrition 0.000 claims abstract description 6
- 241001670235 Artemisia rupestris Species 0.000 claims abstract description 6
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- 239000000284 extract Substances 0.000 claims description 102
- 238000010992 reflux Methods 0.000 claims description 66
- 239000010231 banlangen Substances 0.000 claims description 60
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- 239000000843 powder Substances 0.000 claims description 40
- 241000628997 Flos Species 0.000 claims description 28
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- -1 reflux Substances 0.000 claims description 11
- ZFHSKBJBODQVBX-AXTRIDKLSA-N Pechueloic acid Chemical compound C[C@H]1CC[C@@H](C(=C)C(O)=O)CC2=C(C)C(=O)C[C@@H]12 ZFHSKBJBODQVBX-AXTRIDKLSA-N 0.000 claims description 10
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- 238000007796 conventional method Methods 0.000 claims description 6
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- 210000004072 lung Anatomy 0.000 abstract description 21
- 241000712461 unidentified influenza virus Species 0.000 abstract description 14
- 230000004083 survival effect Effects 0.000 abstract description 9
- 241000699670 Mus sp. Species 0.000 abstract description 7
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- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 6
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Abstract
The invention relates to the technical field of cold drugs and preparation methods thereof and in particular relates to an anti-influenza drug and a preparation method thereof. The anti-influenza drug is prepared from the raw materials in parts by weight: 1-3 parts of Artemisia rupestris, 1-3 parts of isatidis root and 1-3 parts of globeflower. With the adoption of the anti-influenza drug, average IC50 (Half Maximal Inhibitory Concentration) of the anti-influenza drug to an influenza A virus and an influenza B virus are respectively 115.86 micrograms/ml and 132.28 micrograms/ml, and average TI (Therapeutic Index) of the anti-influenza drug to the influenza A virus and the influenza B virus are respectively 8.8 and 7.7; a 0.2g/kg dosage group of the anti-influenza drug is capable of obviously prolonging survival days of a mice which is infected by the influenza A virus, and the death rate is lowered; a 0.1g/kg dosage group and the 0.2g/kg dosage group are capable of obviously inhibiting a lung exponential value, and average inhibition ratios are respectively 19.4 percent and 28.0 percent. The anti-influenza drug has certain actions of preventing the influenza virus in vivo and in vitro and provides the pharmacology basis for treating influenza.
Description
Technical field
the present invention relates to medicine and preparation method thereof technical field for flu, is that a kind of influenza emits medicine and preparation method thereof.
Background technology
influenza (abbreviation influenza) is the Acute respiratory infectious disease being caused by influenza virus (influenza virus, 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 mortality rates necessarily.
influenza is the Acute respiratory infectious disease of a kind of harm humans health of being 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 to surpass 20,000,000 people's death.Approximately between every 10 years, all can occur being very popular of an influenza subsequently, its main cause is that influenza virus passes through hereditary variation fast, thereby the human immune system's that escaped identification, kills and remove.China is one of country of taking place frequently of influenza, and influenza has caused grave danger to people's health.The Chinese government always payes attention to the prevention and control of influenza, in nineteen fifty-seven, has set up national influenza center, within 1981, recovers to have added the international Influenza Surveillance net of WHO, and 31 provinces in the whole nation (municipality directly under the Central Government, autonomous region) 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, rules, takes strong measure, uses the method means of science, has effectively controlled the diffusion of bird flu and has 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 bring into play desirable effect; And China's natural resources of Chinese medicinal materials is abundant, research and use with a long history, meanwhile, Chinese medicine has the features such as flu-prevention occurs, action target spot is many, few side effects.Chinese medicine prevention viral disease has following characteristic and advantage: 1., when treatment viral infection 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.Can analyze its pathology development 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 one hand; 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 be with reference to traditional square medicine.Can effectively alleviate the infected's pathological lesion on the whole, not only emphasized eliminating evil but also paid attention to body self-regulation.Therefore, make full use of Chinese medicine resource, contribute to us to solve a difficult problem for influenza infection.But Chinese medicine traditional decoction adopts traditional decoct mostly, its amount of water, to decoct the factors 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 to develop the Chinese medicine novel form that is applicable to industrialization.
Summary of the invention
the invention provides a kind of influenza and emit medicine and preparation method thereof, overcome the deficiency of above-mentioned prior art, it can effectively solve, and Western medicine is difficult to bring into play desirable effect and Chinese medicine traditional decoction is large on clinical efficacy impact, taking dose is large and carry inconvenient problem.
one of technical scheme of the present invention realizes by following measures: a kind of influenza emits medicine, and raw materials by weight portion consists of 1 part to 3 parts of Herba Achilleae, 1 part to 3 parts of Radix Isatidis, 1 part to 3 parts of Flos Trollii.
the further optimization and/or improvements to one of foregoing invention technical scheme below:
above-mentioned influenza emits medicine to obtain as follows, the first step, the Radix Isatidis powder of aequum is broken into Radix Isatidis coarse powder, the water soaking 24h to 48h that adds 6 times to 10 times Radix Isatidis coarse powder weight in Radix Isatidis coarse powder, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 ℃ to 110 ℃, each reflux extracting time is 0.5h to 1.5h, after each reflux, extract,, filter and obtain aqueous extract and medicinal residues, then in the medicinal residues after filtration, add the water of 6 times to 10 times Radix Isatidis coarse powder weight once to extract on carrying out, after reflux, extract, like this 2 times to 4 times, the aqueous extract at every turn obtaining is combined and obtains water extraction mixed liquor, it is that density at 60 ℃ is 1.22 to 1.25 clear paste that water extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then will after clear paste vacuum drying, obtain Radix Isatidis extract, the quality single-detector of Radix Isatidis extract is less than or equal to 6%,
second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtain mixing medical material, in mixing medical material, add and mix 8 times of ethanol waters to 12 times of weight of medical material, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 ℃ to 100 ℃, each reflux extracting time is 1h to 3h, after each reflux, extract,, filter and obtain alcohol extract and medicinal residues, then in the medicinal residues after filtration, add mix 8 times of ethanol waters to 12 times of weight of medical material carry out on reflux, extract, once, after reflux, extract, like this 2 times to 4 times, the alcohol extract at every turn obtaining is combined and obtains alcohol extraction mixed liquor, it is that density at 60 ℃ is 1.22 to 1.25 clear paste that alcohol extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the quality single-detector of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
the 3rd step, after Radix Isatidis extract is mixed homogeneously with the mixed extract of Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains influenza and emit medicine.
in above-mentioned Radix Isatidis, the quality percentage composition of (R, S)-goitrin is 0.055% to 0.075%.
the quality percentage composition 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 ℃ to 65 ℃; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, vacuum drying temperature is 55 ℃ to 65 ℃; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with can be no more than 20% powder by No. three sieves or/and, in second step, ethanol water is that concentration of volume percent is 60% to 80% ethanol water.
two of technical scheme of the present invention realizes by following measures: a kind of influenza emits the preparation method of medicine, 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 that adds 6 times to 10 times Radix Isatidis coarse powder weight in Radix Isatidis coarse powder, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 ℃ to 110 ℃, each reflux extracting time is 0.5h to 1.5h, after each reflux, extract,, filter and obtain aqueous extract and medicinal residues, then in the medicinal residues after filtration, add the water of 6 times to 10 times Radix Isatidis coarse powder weight once to extract on carrying out, after reflux, extract, like this 2 times to 4 times, the aqueous extract at every turn obtaining is combined and obtains water extraction mixed liquor, it is that density at 60 ℃ is 1.22 to 1.25 clear paste that water extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then will after clear paste vacuum drying, obtain Radix Isatidis extract, the quality single-detector of Radix Isatidis extract is less than or equal to 6%,
second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtain mixing medical material, in mixing medical material, add and mix 8 times of ethanol waters to 12 times of weight of medical material, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 ℃ to 100 ℃, each reflux extracting time is 1h to 3h, after each reflux, extract,, filter and obtain alcohol extract and medicinal residues, then in the medicinal residues after filtration, add mix 8 times of ethanol waters to 12 times of weight of medical material carry out on reflux, extract, once, after reflux, extract, like this 2 times to 4 times, the alcohol extract at every turn obtaining is combined and obtains alcohol extraction mixed liquor, it is that density at 60 ℃ is 1.22 to 1.25 clear paste that alcohol extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the quality single-detector of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
the 3rd step, after Radix Isatidis extract is mixed homogeneously with the mixed extract of Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains influenza and emit medicine.
the further optimization and/or improvements to two of foregoing invention technical scheme below:
in above-mentioned Radix Isatidis, the quality percentage composition of (R, S)-goitrin is 0.055% to 0.075%.
the quality percentage composition 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 ℃ to 65 ℃; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, vacuum drying temperature is 55 ℃ to 65 ℃; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with can be no more than 20% powder by No. three sieves or/and, in second step, ethanol water is that concentration of volume percent is 60% to 80% ethanol water.
influenza of the present invention emits medicine to be respectively 115.86 μ g/ml, 132.28 μ g/ml to the average IC50 of first, Influenza B virus, and average T I is 8.8,7.7; Influenza of the present invention emits medicine 0.2g/kg dosage group can obviously extend influenza a virus infection mouse survival natural law, reduces mortality rate; 0.1g/kg, 0.2g/kg dosage group can obviously suppress lung exponential quantity, and average suppression ratio is respectively 19.4%, 28.0%; Influenza of the present invention emits that medicine has in certain body, the effect of In Vitro Anti influenza virus, for it is used for the treatment of influenza, provides pharmacology foundation.
The specific embodiment
the present invention is not subject to the restriction of following embodiment, can determine concrete embodiment according to technical scheme of the present invention and practical situation.
embodiment 1, and this influenza emits medicine, and raw materials by weight portion consists of 1 part to 3 parts of Herba Achilleae, 1 part to 3 parts of Radix Isatidis, 1 part to 3 parts of Flos Trollii.
embodiment 2, and this influenza emits medicine, and raw materials by weight portion consists of 1 part of 1 part of Herba Achilleae or 3 parts, Radix Isatidis or 3 parts, 1 part or 3 parts of Flos Trollii.
embodiment 3, this influenza emits medicine to obtain 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 that adds 6 times to 10 times Radix Isatidis coarse powder weight in Radix Isatidis coarse powder, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 ℃ to 110 ℃, each reflux extracting time is 0.5h to 1.5h, after each reflux, extract,, filter and obtain aqueous extract and medicinal residues, then in the medicinal residues after filtration, add the water of 6 times to 10 times Radix Isatidis coarse powder weight once to extract on carrying out, after reflux, extract, like this 2 times to 4 times, the aqueous extract at every turn obtaining is combined and obtains water extraction mixed liquor, it is that density at 60 ℃ is 1.22 to 1.25 clear paste that water extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then will after clear paste vacuum drying, obtain Radix Isatidis extract, the quality single-detector of Radix Isatidis extract is less than or equal to 6%,
second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtain mixing medical material, in mixing medical material, add and mix 8 times of ethanol waters to 12 times of weight of medical material, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 ℃ to 100 ℃, each reflux extracting time is 1h to 3h, after each reflux, extract,, filter and obtain alcohol extract and medicinal residues, then in the medicinal residues after filtration, add mix 8 times of ethanol waters to 12 times of weight of medical material carry out on reflux, extract, once, after reflux, extract, like this 2 times to 4 times, the alcohol extract at every turn obtaining is combined and obtains alcohol extraction mixed liquor, it is that density at 60 ℃ is 1.22 to 1.25 clear paste that alcohol extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the quality single-detector of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
the 3rd step, after Radix Isatidis extract is mixed homogeneously with the mixed extract of Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains influenza and emit medicine.
embodiment 4, this influenza emits medicine to obtain by following preparation method, the first step, the Radix Isatidis powder of aequum is broken into Radix Isatidis coarse powder, the water soaking 24h or the 48h that in Radix Isatidis coarse powder, add 6 times or 10 times Radix Isatidis coarse powder weight, reflux, extract, 2 times or 4 times, the temperature of each reflux, extract, is 80 ℃ or 110 ℃, each reflux extracting time is 0.5h or 1.5h, after each reflux, extract,, filter and obtain aqueous extract and medicinal residues, then in the medicinal residues after filtration, add the water of 6 times or 10 times Radix Isatidis coarse powder weight once to extract on carrying out, after reflux, extract, like this 2 times or 4 times, the aqueous extract at every turn obtaining is combined and obtains water extraction mixed liquor, it is that density at 60 ℃ is 1.22 or 1.25 clear paste that water extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then will after clear paste vacuum drying, obtain Radix Isatidis extract, the quality single-detector of Radix Isatidis extract is less than or equal to 6%,
second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtain mixing medical material, in mixing medical material, add the ethanol water that mixes 8 times or 12 times weight of medical material, reflux, extract, 2 times or 4 times, the temperature of each reflux, extract, is 80 ℃ or 100 ℃, each reflux extracting time is 1h or 3h, after each reflux, extract,, filter and obtain alcohol extract and medicinal residues, then in the medicinal residues after filtration, add the ethanol water that mixes 8 times or 12 times weight of medical material carry out on reflux, extract, once, after reflux, extract, like this 2 times or 4 times, the alcohol extract at every turn obtaining is combined and obtains alcohol extraction mixed liquor, it is that density at 60 ℃ is 1.22 or 1.25 clear paste that alcohol extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the quality single-detector of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
the 3rd step, after Radix Isatidis extract is mixed homogeneously with the mixed extract of Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains influenza and emit medicine.
embodiment 5, and as the optimization of above-described embodiment, in the Radix Isatidis of embodiment 5, the quality percentage composition of (R, S)-goitrin is 0.055% to 0.075%.
embodiment 6, and as the optimization of above-described embodiment, the quality percentage composition of the Rupestonic Acid in Artemisia Rupestris L. Growing of embodiment 6 is 0.30% to 0.45%.
embodiment 7, and as the optimization of above-described embodiment, in the first step and second step of embodiment 7, the pressure of concentrating under reduced pressure is 0.08Mpa, and the temperature of concentrating under reduced pressure is 55 ℃ to 65 ℃; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, vacuum drying temperature is 55 ℃ to 65 ℃; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with can be no more than 20% powder by No. three sieves or/and, in second step, ethanol water is that concentration of volume percent is 60% to 80% ethanol water.
the influenza obtaining according to the above embodiment of the present invention emits the pharmacodynamic experiment of medicine as follows:
1, the influenza that the above embodiment of the present invention obtains emits the toxicity of medicine to mdck cell
the influenza that the above embodiment of the present invention is obtained emits medicine and existing public influenza to emit medicine ribavirin by maintenance medium, to dilute respectively, by adding respectively the maintenance medium of 2 ml, 4 ml, 8ml, 16ml, 32 ml, 64 ml and 128 ml in every μ g, be configured to respectively 1:2,1:4,1:8,1:16,1:32,1:64 and 1:128 totally seven concentration, be added to inoculation mdck cell and grown up in 96 well culture plates of monolayer, 100 μ l/ holes, cell contrast is established in 4 multiple holes of every dilution factor simultaneously.Culture plate is put to 37
o
c, 5% CO
2
in incubator, cultivate, 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 influenza that the above embodiment of the present invention obtains emits medicine to show as cell proliferation to the toxic action of mdck cell, granule is more, form changes, part cell breakage comes off, toxic action to mdck cell alleviates along with the reduction of drug level, illustrate influenza that the above embodiment of the present invention obtains emit medicine and ribavirin effective equally to mdck cell; Average T C to MDCK cultured cell
0
with average TC
50
in Table 1.
the influenza that test example 2, the above embodiment of the present invention obtain emits the impact of medicine on pathological changes caused by virus (CPE)
get the culture plate of inoculating mdck cell and growing up to monolayer, inhale and abandon culture fluid, inoculate respectively the tissue culture infective dose (100TCID of 100 times
50
) different virus liquid 50 μ l, put 37
o
c, 5% CO
2
in incubator, adsorb after 1 hour, inhale and abandon virus liquid, use Eagle
,
s maintenance medium is washed cell surface 2 times, establishes cell matched group, virus control group, ribavirin variable concentrations and (gets TC
0
and three following 4 times of dilution factors totally four concentration), the influenza that the above embodiment of the present invention obtains emits medicine variable concentrations (to get TC
0
and three following 2 times of dilution factors totally four concentration) administration group, 4 holes/group; Administration group adds different dilution medicinal liquids, and matched group adds maintenance medium, 100 μ l/ holes.Culture plate puts 37
o
c, 5% CO
2
in incubator, cultivate, observation of cell pathological changes situation under every day inverted microscope records experimental result when virus control group cytopathy reaches 4 grades.Cytopathy judges by six grade standards, and presses Reed-Muench method and calculate 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 below 25% of whole cell monolayer;
2: cytopathy accounts for below 50% of whole cell monolayer;
3: cytopathy accounts for below 75% of whole cell monolayer;
4: cytopathy accounts for the more than 75% of whole cell monolayer.
the influenza that the above embodiment of the present invention obtains emits medicine to have 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 impact that the influenza that the above embodiment of the present invention obtains emits medicine and ribavirin to cause mdck cell pathological changes to virus is shown in Table 2; The influenza that the above embodiment of the present invention obtains emits medicine and ribavirin to the results are shown in Table shown in 3 antiviral study in vitro.
the influenza that test example 3, the above embodiment of the present invention obtain emits the impact of medicine on infecting mouse mortality rate and life span
healthy kunming mice is divided into 6 groups at random by sex body weight, be that the influenza that model control group, ribavirin group, antiviral granule group, the above embodiment of the present invention obtain emits three dosed administration groups of medicine, every group 12, the continuous gastric infusion of each administration group 10 days, once-a-day, matched group is to distilled water, 2h after administration on the 3rd, and except Normal group, all the other respectively organize mice respectively with 10LD
50
virus liquid collunarium infect, observe day by day animal incidence and record death toll, after infecting, within the 14th day, calculate dead protective rate and increase in life span.
dead protective 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; It is respectively 41.7 and 33.3 that the influenza that the above embodiment of the present invention obtains emits the average mortality of medicine 0.1g/kg, 0.2g/kg dosage group; compare with model control group and there is significant difference (P<0.01); the influenza that the above embodiment of the present invention obtains emits the protective effect of medicine influenza virus infected suitable with the effect of positive control drug antiviral granule, on the impact of infecting mouse mortality rate in Table 4.
the mean survival time of model control group is compared obvious shortening with matched group, there is significant difference (P<0.01), it is 12.00 ± 2.66 that the influenza that the above embodiment of the present invention obtains emits the medicine 0.2g/kg dosage group mean survival time, compare obvious prolongation with model control group and have notable difference (P<0.01), its effect is better than antiviral granule; The influenza that the above embodiment of the present invention obtains emits medicine 0.05g/kg, 0.1g/kg dosage group mean survival time to compare also obviously prolongation with model control group, be respectively 9.25 ± 3.11 and 10.33 ± 3.55, but compare there was no significant difference with model control group; On the impact of infecting mouse life span in Table 5.
the influenza that test example 4, the above embodiment of the present invention obtain emits the impact of medicine on Lung Index of mice infected by Influenza virus
healthy kunming mice is divided into 6 groups at random by sex body weight, be that the influenza that Normal group, model control group, antiviral granule group, the above embodiment of the present invention obtain emits three dosed administration groups of medicine, every group 12, the continuous gastric infusion of each administration group 9 days, once-a-day, matched group is to distilled water, 2h after administration on the 3rd, except Normal group, each organize mice all under the slight anesthesia of ether respectively with 15LD
50
virus liquid 50ul collunarium infect, Normal group is with method collunarium normal saline 50ul.24h after last administration, each is organized, and after mice is weighed, to pluck eyeball blood-letting lethal, takes out full lung after mice is soaked in to 75% ethanol on aseptic operating platform, with normal saline washed twice, with filter paper, blot surperficial moisture content, claim lung weight, the lungs of observing animal change, and calculate lung exponential sum lung suppression ratio.
lung index=lung weight/body weight * 100
lung index=(the average lung index of the average lung index-experimental group of model control group) the average lung of/model control group index * 100
result, model control group is compared with Normal group has significant difference (P<0.01), the influenza that the above embodiment of the present invention obtains emits the lung exponential sum lung suppression ratio of medicine 0.2g/kg dosage group to be respectively 1.34 ± 0.44 and 28.0%, compare with model control group and have significant difference (P<0.01), its effect is suitable with antiviral granule; The influenza that the above embodiment of the present invention obtains emits the lung exponential sum lung suppression ratio of medicine 0.1g/kg dosage group to be respectively 1.50 ± 0.41 and 19.4%, compare with model control group and there is notable difference (P<0.05), and the influenza that the above embodiment of the present invention obtains emits medicine 0.05g/kg dosage group lung index to compare also obviously reduction with model control group, but without significant difference; On the impact of Lung Index of mice infected by Influenza virus in Table 6.
influenza of the present invention emits medicine to be respectively 115.86 μ g/ml, 132.28 μ g/ml to the average IC50 of first, Influenza B virus, and average T I is respectively 8.8,7.7; Influenza of the present invention emits medicine 0.2g/kg dosage group can obviously extend influenza a virus infection mouse survival natural law, reduces mortality rate; Influenza of the present invention emits medicine 0.1g/kg, 0.2g/kg dosage group can obviously suppress lung exponential quantity, and suppression ratio is respectively 19.4%, 28.0%.Result of study by pharmacodynamic experiment is known, influenza of the present invention emits that medicine has in certain body, the effect of In Vitro Anti influenza virus, in its body, resisiting influenza virus effect is better than antiviral granule, for it is used for the treatment of influenza, provides pharmacology foundation.
above technical characterictic has formed embodiments of the invention, and it has stronger adaptability and implementation result, can increase and decrease according to actual needs non-essential technical characterictic, meets the demand of different situations.
Claims (9)
1. influenza emits a medicine, it is characterized in that raw materials by weight portion consists of 1 part to 3 parts of Herba Achilleae, 1 part to 3 parts of Radix Isatidis, 1 part to 3 parts of Flos Trollii.
2. influenza according to claim 1 emits medicine, it is characterized in that obtaining as follows, the first step, the Radix Isatidis powder of aequum is broken into Radix Isatidis coarse powder, the water soaking 24h to 48h that adds 6 times to 10 times Radix Isatidis coarse powder weight in Radix Isatidis coarse powder, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 ℃ to 110 ℃, each reflux extracting time is 0.5h to 1.5h, after each reflux, extract,, filter and obtain aqueous extract and medicinal residues, then in the medicinal residues after filtration, add the water of 6 times to 10 times Radix Isatidis coarse powder weight once to extract on carrying out, after reflux, extract, like this 2 times to 4 times, the aqueous extract at every turn obtaining is combined and obtains water extraction mixed liquor, it is that density at 60 ℃ is 1.22 to 1.25 clear paste that water extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then will after clear paste vacuum drying, obtain Radix Isatidis extract, the quality single-detector of Radix Isatidis extract is less than or equal to 6%,
Second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtain mixing medical material, in mixing medical material, add and mix 8 times of ethanol waters to 12 times of weight of medical material, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 ℃ to 100 ℃, each reflux extracting time is 1h to 3h, after each reflux, extract,, filter and obtain alcohol extract and medicinal residues, then in the medicinal residues after filtration, add mix 8 times of ethanol waters to 12 times of weight of medical material carry out on reflux, extract, once, after reflux, extract, like this 2 times to 4 times, the alcohol extract at every turn obtaining is combined and obtains alcohol extraction mixed liquor, it is that density at 60 ℃ is 1.22 to 1.25 clear paste that alcohol extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the quality single-detector of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
The 3rd step, after Radix Isatidis extract is mixed homogeneously with the mixed extract of Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains influenza and emit medicine.
3. influenza according to claim 1 and 2 emits medicine, and the quality percentage composition that it is characterized in that (R, S) in Radix Isatidis-goitrin is 0.055% to 0.075%.
4. according to the influenza described in claim 1 or 2 or 3, emit medicine, the quality percentage composition that it is characterized in that Rupestonic Acid in Artemisia Rupestris L. Growing is 0.30% to 0.45%.
5. according to the influenza described in claim 2 or 3 or 4, emit the preparation method of medicine, it is characterized in that in the 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 ℃ to 65 ℃; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, vacuum drying temperature is 55 ℃ to 65 ℃; Or/and Radix Isatidis coarse powder is all to sieve by No. 1, but be mixed with, can be no more than 20% powder by No. three sieves; Or/and in second step, ethanol water is that concentration of volume percent is 60% to 80% ethanol water.
6. an influenza according to claim 1 emits the preparation method of medicine, 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 that adds 6 times to 10 times Radix Isatidis coarse powder weight in Radix Isatidis coarse powder, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 ℃ to 110 ℃, each reflux extracting time is 0.5h to 1.5h, after each reflux, extract,, filter and obtain aqueous extract and medicinal residues, then in the medicinal residues after filtration, add the water of 6 times to 10 times Radix Isatidis coarse powder weight once to extract on carrying out, after reflux, extract, like this 2 times to 4 times, the aqueous extract at every turn obtaining is combined and obtains water extraction mixed liquor, it is that density at 60 ℃ is 1.22 to 1.25 clear paste that water extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then will after clear paste vacuum drying, obtain Radix Isatidis extract, the quality single-detector of Radix Isatidis extract is less than or equal to 6%,
Second step, the Herba Achilleae of aequum and Flos Trollii are mixed and obtain mixing medical material, in mixing medical material, add and mix 8 times of ethanol waters to 12 times of weight of medical material, reflux, extract, 2 times to 4 times, the temperature of each reflux, extract, is 80 ℃ to 100 ℃, each reflux extracting time is 1h to 3h, after each reflux, extract,, filter and obtain alcohol extract and medicinal residues, then in the medicinal residues after filtration, add mix 8 times of ethanol waters to 12 times of weight of medical material carry out on reflux, extract, once, after reflux, extract, like this 2 times to 4 times, the alcohol extract at every turn obtaining is combined and obtains alcohol extraction mixed liquor, it is that density at 60 ℃ is 1.22 to 1.25 clear paste that alcohol extraction mixed liquor concentrating under reduced pressure is obtained in temperature, then the mixed extract of Herba Achilleae and Flos Trollii will be obtained after clear paste vacuum drying, the quality single-detector of the mixed extract of Herba Achilleae and Flos Trollii is less than or equal to 6%,
The 3rd step, after Radix Isatidis extract is mixed homogeneously with the mixed extract of Herba Achilleae and Flos Trollii, makes tablet or capsule or granule or micropill by conventional method and obtains influenza and emit medicine.
7. influenza according to claim 6 emits the preparation method of medicine, and the quality percentage composition that it is characterized in that (R, S) in Radix Isatidis-goitrin is 0.055% to 0.075%.
8. according to the influenza described in claim 6 or 7, emit the preparation method of medicine, the quality percentage composition that it is characterized in that Rupestonic Acid in Artemisia Rupestris L. Growing is 0.30% to 0.45%.
9. according to the influenza described in claim 6 or 7 or 8, emit the preparation method of medicine, it is characterized in that in the 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 ℃ to 65 ℃; Or/and in the first step and second step, vacuum drying pressure is 0.08Mpa, vacuum drying temperature is 55 ℃ to 65 ℃; Or/and Radix Isatidis coarse powder is all by No. 1 sieve, but be mixed with can be no more than 20% powder by No. three sieves or/and, in second step, ethanol water is that concentration of volume percent is 60% to 80% ethanol water.
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| CN106039277A (en) * | 2016-08-05 | 2016-10-26 | 王豪鹏 | Compound Neelubar cold-treating granules and production method thereof |
| CN109010538A (en) * | 2018-10-11 | 2018-12-18 | 田国荣 | Compound Artemisia rupestris piece |
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