CN101361891B - Traditional Chinese medicine combination for treating grippe and preparation method thereof - Google Patents
Traditional Chinese medicine combination for treating grippe and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a traditional Chinese medicine combination for curing influenza and a preparation method thereof. The combination is prepared from rhizome paridis and hypericum perforatum or from the extract products of rhizome paridis and hypericum perforatum. The traditional Chinese medicine combination is a medicine for resisting H1N1 virus and H3N2 virus with high efficacy and low toxin, and has excellent effect in curing influenza.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition and preparation method thereof, particularly grippal Chinese medicine composition of treatment and preparation method thereof.
Background technology
Influenza is the acute respiratory infectious disease that is caused by influenza virus, is one of main public health problem of facing of the mankind.According to statistics, the sickness rate in influenza every year is 10%～30%, and the outstanding feature of its epidemiology is: outburst suddenly, and rapid spread is broadcast and wide; Influenza pandemic has certain seasonality, and northern China often betides winter, and mostly occurs in two seasons of summer in winter in south; The sickness rate height of influenza, the general susceptible of crowd.The influenza clinical symptoms is heavier, and onset is rapid, the complication rate height, and can cause death, dead person mostly is old asthenia, young many diseases greatly or chronic underlying diseases person is arranged.1918 of 20th century, nineteen fifty-seven and nineteen sixty-eight break out in the whole world 3 times, have the tens of millions of people to be seized life by influenza.According to the report of U.S. Science and Technology Commission, in recent years the U.S. to die from the number of influenza every year be 2～40,000, influenza becomes the highest viral infectious of fatality rate.China is the district occurred frequently of influenza, and 20th century 4 times are global has been very popular 3 times to originate from China.
The doctor trained in Western medicine aspect is in the problem of grippal present situation of clinical treatment and existence: influenza belongs to self-limited disease, and the purpose of Drug therapy is relief of symptoms, shortens the course of disease, prevents and treats complication.Its nosetiology treatment at present mainly contains following two class medicines: neuraminidase inhibitor (Oseltamir; Zanamivir) and ion channel M2 inhibitor (Am-antadine; Rimantadine).Treatment should be used in morbidity 48h, and early stage application can stop PD, alleviates the state of an illness, improve prognosis.Two kinds of glycoprotein projections are arranged, i.e. hemagglutinin (HA) and neuraminidase (NA) on the influenza virus.According to the antigenicity difference, influenza virus is divided into first, second, the third 3 types.Influenza A virus often occurs with popular form, can cause worldwide being very popular; The B-mode influenza part that often causes is broken out; Third type mainly occurs to distribute form.The crowd can produce immunity by infecting or inoculating, but new variant viral strain be there is no protective effect.Because the influenza antigen variation is very fast, so the mankind can't obtain persistent immunity.Think that at present influenza vaccinations are the most effective means of flu-prevention.But the influenza antigen mutability, and be difficult to control, so often cause poor effect, this also is the popular one of the main reasons of not controlling fully as yet so far of influenza.Real epidemic strain vaccine can't be produced and lay in advance, only after the generation of being very popular, just can be separated to real epidemic strain, prepares according to this then and simulates the antigenic vaccine of epidemic strain as far as possible.The effectiveness of influenza vaccines depends on vaccine receptor's the immune functional state and the dna homolog of Strain in the vaccine and epidemic diseases strain.Therefore, although existing influenza vaccines have been a kind of sophisticated commercialized vaccine, still be worth further research and discussion.The resisiting influenza virus treatment is the important means of influenza control, but the clinical shortage that is in substantially is at the direct acting active drug of virus.Raising reduces influenza to the significant damage that society causes to the early diagnosis level of influenza, carry out treatment in early days, has the important clinical realistic meaning.Therefore, the seek treatment active drug of influenza is pressing for of clinical practice.
The traditional Chinese medical science thinks that the gas when influenza is non-holds six climate exopathogens seasonal pathogen invasion and attack human body under the arm and cause a disease, and genus " influenza ", " epidemic febrile disease caused by exogenous pathogens ", " pathogenic wind-warm " reach the category of " pestilence "; The traditional Chinese medical science can chase after north remote to the understanding of influenza.The sick position of the morbidity of influenza is defended at lung, that is alleged " influenza " of the traditional Chinese medical science, is by due to epidemic disease due to heat pathogen, the cold eqpidemic disease poison intrusion human body.The evil convict of six climate exopathogens must be pressed from both sides epidemic disease virus, prolongs blessing as the Qingxu and says: " the nontoxic not convict of the heresy of six climate exopathogens " (" the trivial speech of doctor doctor ").Three approach of epidemic disease convict: the one heresy by on be subjected to, invade the criminal's of defending lung; Its two straight criminals nutrient blood, the pathogen attacking the pericardium adversely, gods are got involved, and brains are unfavorable, and the machine key is obstructed; Though three heresies by on be subjected to, the middle road that directly becomes lies prostrate in pleurodiaphragmatic in terspace, in see that taste are dull, see that outward to defend gas stranded.Epidemic disease is many is gone into by respiratory tract, and its evil visitor of institute starts from and defends gas.Defend gas and be the evil Shu Buneng of institute drive evil in outside, epidemic disease is evil to be satisfied to be invaded by air flue and hinders in lung, is involved in stomach by the channels of lung.Heavy then by battalion and blood, battalion defends to lose withers, and can not refuse heresy, overtaxes one's nerves bright by the blood road.And the attacking the people and whether fall ill of heresy lain in power few more than the prosperity and decline, epidemic disease poison of healthy energy, poison entirely.Chinese medicine preparation is many to be target with the treatment common cold, the traditional compound recipe of the many genus of prescription compatibility, and how not fully aware of targeting and target spot be; Aspects such as function mainly concentrates on relieving the exterior syndrome with drugs of pungent in flavor and warm in nature, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature, the dehumidifying of inducing sweat.
Summary of the invention
First purpose of the present invention is to disclose the grippal Chinese medicine composition of a kind of treatment.
Second purpose of the present invention is to disclose a kind of preparation method for the treatment of grippal Chinese medicine composition.
The 3rd purpose of the present invention is the open grippal Chinese medicine composition of being made up of Rhizoma Paridis, Herba Hyperici perforati effective site of treatment, and said composition has realized that targeting, the target spot of treatment is clearer and more definite.
The 4th purpose of the present invention is to disclose the method for preparing drop pills of the grippal Chinese medicine composition of being made up of Rhizoma Paridis, Herba Hyperici perforati effective site of treatment.
The 5th purpose of the present invention is to disclose a kind of extracting method of Rhizoma Paridis, and the content of the total saponins that this method is extracted can reach more than 70%.
The 6th purpose of the present invention is to disclose a kind of extracting method of Herba Hyperici perforati, and the general flavone content that this method is extracted can reach more than 60%.
First purpose of the present invention is achieved by the following technical solution:
The grippal Chinese medicine composition of a kind of treatment, make by the raw material of following weight ratio:
Rhizoma Paridis 3-15 weight portion, Herba Hyperici perforati 3-9 weight portion.
The grippal Chinese medicine composition of described treatment, preferably make by the raw material of following weight ratio:
Rhizoma Paridis 8-10 weight portion, Herba Hyperici perforati 5-8 weight portion.
The grippal Chinese medicine composition of described treatment, preferably make by the raw material of following weight ratio:
Rhizoma Paridis 9 weight portions, Herba Hyperici perforati 6 weight portions.
Above-mentioned a kind of preparation method for the treatment of grippal Chinese medicine composition can be selected any one in the following method for use:
1, get Rhizoma Paridis 3-15 weight portion, Herba Hyperici perforati 3-9 weight portion adds ethanol extraction 2-3 time of 60-80%, and the 4-8 that each ethanol consumption is the medical material amount is (weight ratio) doubly, extracts 1-2 hour at every turn, and merge extractive liquid, reclaims ethanol to there not being the alcohol flavor, promptly gets extracting solution;
2, get Rhizoma Paridis 3-15 weight portion, Herba Hyperici perforati 3-9 weight portion adds ethanol extraction 2-3 time of 60-80%, and the 4-8 that each ethanol consumption is the medical material amount is (weight ratio) doubly, extracts 1-2 hour at every turn, and merge extractive liquid, reclaims ethanol to there not being the alcohol flavor, promptly gets extracting solution; Said extracted liquid is filtered, and filtrate is by macroporous resin, and with the ethanol elution of 4-6 times of water gaging or 20% following concentration, eluent is abandoned or adopted earlier, and reuse adds 1-10 times of eluting of 50-80% ethanol, the collection eluent, and decompression recycling ethanol gets the purification extracting solution to there not being the alcohol flavor.
3, get Rhizoma Paridis 3-15 weight portion, Herba Hyperici perforati 3-9 weight portion decocts with water 2-3 time, and the 6-12 that each water consumption is the medical material amount is (weight ratio) doubly, extracts 1-2 hour at every turn, and merge extractive liquid, filters, and promptly gets extracting solution; Said extracted liquid is filtered, and filtrate is by macroporous resin, and with the ethanol elution of 4-6 times of water gaging or 20% following concentration, eluent is abandoned or adopted earlier, and reuse adds 1-10 times of eluting of 50-80% ethanol, the collection eluent, and decompression recycling ethanol gets the purification extracting solution to there not being the alcohol flavor.
Above-mentioned a kind of preparation method for the treatment of grippal Chinese medicine composition can be made through the extraction process of routine [as model Bi Ting " pharmacy of Chinese materia medica " (Shanghai Science Press 1997 December the 1st edition)] by the above-mentioned raw materials medicine.
Above-mentioned Rhizoma Paridis, Herba Hyperici perforati can be made the acceptable any conventional dosage form of pharmaceutics by preparation process routinely after extracting, comprise capsule, tablet, granule, gel, slow releasing agent, oral liquid.
For above-mentioned dosage form can be realized, need when these dosage forms of preparation, to add the pharmacy acceptable auxiliary, for example: filler, disintegrating agent, lubricant, suspending agent, binding agent, sweeting agent, correctives, antiseptic, substrate etc.Filler comprises: starch, pregelatinized Starch, lactose, mannitol, chitin, microcrystalline Cellulose, sucrose etc.; Disintegrating agent comprises: starch, pregelatinized Starch, microcrystalline Cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose etc.; Lubricant comprises: magnesium stearate, sodium lauryl sulphate, Pulvis Talci, silicon dioxide etc.; Suspending agent comprises: polyvinylpyrrolidone, microcrystalline Cellulose, sucrose, agar, hydroxypropyl emthylcellulose etc.; Binding agent comprises, starch slurry, polyvinylpyrrolidone, hydroxypropyl emthylcellulose etc.; Sweeting agent comprises: saccharin sodium, Aspartane, sucrose, cyclamate, enoxolone etc.; Correctives comprises: sweeting agent and various essence; Antiseptic comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its esters, benzalkonium bromide, fixed, the Folium eucalypti globueli (Eucalyptus globulus Labill.) wet goods of acetic acid chloroethene; Substrate comprises: PEG6000, PEG4000, insect wax etc.For making above-mentioned dosage form can realize pharmacy of Chinese materia medica, need when these dosage forms of preparation, to add acceptable other adjuvant of pharmacy (adjuvant of each dosage form record among the Fan Biting " pharmacy of Chinese materia medica ", Shanghai Science Press December in 1997 the 1st edition).
The 3rd purpose of the present invention is the open grippal Chinese medicine composition of being made up of Rhizoma Paridis, Herba Hyperici perforati effective site of treatment, and said composition is made by the crude drug of following weight ratio:
Rhizoma Paridis extract 3-15 weight portion, Herba Hyperici perforati extract 3-9 weight portion.
The grippal Chinese medicine composition of described treatment, preferably make by the crude drug of following weight ratio:
Rhizoma Paridis extract 8-10 weight portion, Herba Hyperici perforati extract 5-8 weight portion.
The grippal Chinese medicine composition of described treatment, preferably make by the crude drug group of following weight ratio:
Rhizoma Paridis extract 9 weight portions, Herba Hyperici perforati extract 6 weight portions.
The preparation method of the described grippal Chinese medicine composition of forming by Rhizoma Paridis, Herba Hyperici perforati effective site of treatment, wherein Rhizoma Paridis extract, Herba Hyperici perforati extract can be by commercially available purchase, make the acceptable any conventional dosage form of pharmaceutics according to above-mentioned prescription ratio and preparation process routinely, comprise drop pill, capsule, tablet, granule, gel, slow releasing agent, oral liquid;
Rhizoma Paridis extract of the present invention can be but be not limited to that the refining thing of post is crossed in alcohol extraction, water was carried post refining thing, ethanol extract or water extract; The total amount of Rhizoma Paridis saponin I, II is greater than 15% in the above-mentioned Rhizoma Paridis extract; Total saponin content is greater than 50%.
Herba Hyperici perforati extract of the present invention (effective site) can be but be not limited to that the refining thing of post is crossed in alcohol extraction, water was carried post refining thing, ethanol extract or water extract; The content of hypericin is greater than 0.3% in the above-mentioned Herba Hyperici perforati extract, and general flavone content is greater than 15%.
Rhizoma Paridis of the present invention, Herba Hyperici perforati alcohol extraction cross the refining thing of post, water carried the refining thing of post, ethanol extract or water extract can but be not limited to by following method preparation:
The preparation method of a, Rhizoma Paridis extract:
Get the ethanol that Rhizoma Paridis adds 60-80%, reflux, extract, 3-4 time, each 1-2 hour, the solvent consumption was 4-6 a times of medical material amount, merge extractive liquid, gets the Rhizoma Paridis extracting solution; Or
Get Rhizoma Paridis water extraction 2-3 times, each 1-2 hours, the solvent consumption was 4-6 a times of medical material amount.Merge extractive liquid,, being concentrated into 50-60 ℃ of relative density is 1.1-1.3, adds ethanol and makes concentration of alcohol reach 75%, cold preservation 10-48 hour, filtration added ethanol and makes concentration of alcohol reach 85%, and cold preservation 24-36 hour, filter to clarification, get the Rhizoma Paridis extracting solution.
The preparation method of b, Herba Hyperici perforati extract:
Get Fructus Forsythiae and decoct with water extraction 3-4 time, each 1-2 hour, the solvent consumption was 4-6 a times of medical material amount, merge extractive liquid,, being concentrated into 50-60 ℃ of relative density is 1.1-1.3, adds ethanol and makes concentration of alcohol reach 70%, cold preservation 24-36 hour, filter, reclaim ethanol, add ethanol and make concentration of alcohol reach 80% to there not being the alcohol flavor, cold preservation 24-36 hour, filtration is reclaimed ethanol to there being the ethanol flavor to clarification, gets the Fructus Forsythiae extracting solution;
Get the ethanol that Fructus Forsythiae adds 60-80%, reflux, extract, 3-4 times, each 1-2 hour, the solvent consumption was 4-6 a times of medical material amount, merge extractive liquid, gets the Fructus Forsythiae extracting solution.
C, Rhizoma Paridis, Fructus Forsythiae are crossed the method that post extracts
Above-mentioned Rhizoma Paridis extracting solution, Fructus Forsythiae extracting solution are filtered respectively, filtrate is passed through macroporous resin respectively, first ethanol elution with 4-6 times of water gaging or 20% following concentration, eluent is abandoned or adopted, reuse adds 1-10 times of eluting of 60-90% ethanol, the collection eluent, decompression recycling ethanol gets purification Rhizoma Paridis extracting solution, purification Fructus Forsythiae extracting solution to there not being the alcohol flavor.
The present invention further discloses a kind of extraction Rhizoma Paridis method, this extracting method can make the content of total saponins reach more than 70%, and this method comprises the steps:
Step 1: the Rhizoma Paridis medical material is doubly measured (with the medical material weight ratio) with 7-12 at every turn and was extracted 1-3 hour with 60-80% ethanol extraction 1-4 time; Extracting solution filters, merge extracting solution A;
Step 2: the centrifugal 20-40 of extracting solution A minute, get supernatant B, and collect residue C;
Step 3: supernatant B crosses post, adopt AB-8 resin or D-101 resin, absorption flow velocity 1.5-3.5BV/h, wash with water earlier, volume 4-6BV, reuse 20-40% ethanol elution 4-6BV adopts the 60-80% ethanol elution at last, the eluant consumption is 4-7BV (BV is meant several times column volume), and elution flow rate is 2-4BV/h;
Step 4: the 60-80% ethanol elution is merged with residue C, reclaim ethanol, vacuum drying.
Said extracted Rhizoma Paridis method preferably includes following steps:
Step 1: the Rhizoma Paridis medical material was measured reflux, extract, 2 hours with 10 times for the first time with 70% ethanol extraction twice, extracted 1.5h with 8 times of amounts (weight ratio) for the second time; Extracting solution filters, merge extracting solution A;
Step 2: extracting solution A gets supernatant B with the centrifugal 30min of the speed of 2500rpm, and collects residue C;
Step 3: supernatant B crosses post, adopts the AB-8 resin, last sample concentration (concentration of supernatant) 0.2g/ml, absorption flow velocity 2BV/h, washing volume 5BV, 30% ethanol elution 5BV, eluant is 70% ethanol, and the eluant consumption is 5.5BV (BV is meant several times column volume), and elution flow rate is 3BV/h;
Step 4: 70% ethanol elution is merged with residue, reclaim ethanol, vacuum drying.
The present invention further discloses a kind of extracting method of Herba Hyperici perforati, this method comprises the steps:
Step I: Herba Hyperici perforati is with 70-90% ethanol extraction 2-4 time, and each 1.5-3 hour, the ethanol consumption was that 8-12 doubly measures; Extracting solution filters, and merges, and gets extracting solution a;
Step I i: get the centrifugal 20-40min of extracting solution a, get supernatant b, and collect residue c;
Step I ii: supernatant b adopts HPD-100 resin or D-101 resin, last sample concentration 0.15g/ml, absorption flow velocity 1.5-3BV/h, wash with water earlier, volume is 3-5BV, and reuse 15-25% ethanol elution 4-6BV is the 50-70% ethanol elution with eluant at last, the eluant consumption is 4-6BV, and elution flow rate is 2-4BV/h;
Step I v: the 50-70% eluent is merged with residue, reclaim ethanol, vacuum drying.
The extracting method of described Herba Hyperici perforati is preferably as follows step:
Step I: Herba Hyperici perforati is with 80% ethanol extraction 2 times, each 2.0 hours, 10 times of amounts; Extracting solution filters, and merges;
Step I i: with the centrifugal 30min of the speed of 2500rpm, get supernatant, and collect residue;
Step I ii: adopt HPD-100 resin and D-101 resin, last sample concentration 0.15g/ml, absorption flow velocity 2BV/h, elder generation's water eluting, volume is 4BV, reuse 20% ethanol elution 5BV, be 60% ethanol elution with eluant at last, the eluant consumption is 5BV, and elution flow rate is 3BV/h;
Step I v: 60% ethanol elution is merged with residue, reclaim ethanol, vacuum drying.
The extracting method of above-mentioned Herba Hyperici perforati can make general flavone content reach more than 60%.
The present invention further discloses the method for optimizing of the drop pill preparation of the Chinese medicine composition of being made up of Rhizoma Paridis, Herba Hyperici perforati effective site:
More than or equal to 0.8, substrate is PEG4000:6000=2-4:1 to substrate than the weight ratio of medicine; Wherein PEG4000:6000 is preferably 3:1;
Melt temperature 65-75 ℃, preferred 70 ℃; Condensing agent is a methyl-silicone oil-50; Drip 65～75 ℃ of system temperature, drip, cooling column length 50cm, condensation temperature: ice-water bath apart from 6cm.
From influenza pandemic in the past, how by the viral acute infectious disease that causes of H1N1, H3N2.This sick infectiousness is strong, fatality rate is high, and the mankind are constituted a serious threat.The present invention is a kind of efficient, anti-H1N1 of low toxicity, the medicine of H3N2 virus by directly the feed intake compositions of preparation and Rhizoma Paridis, Herba Hyperici perforati of Rhizoma Paridis, Herba Hyperici perforati crude drug with the feed intake Chinese medicine composition of preparation of form of extract.
The composite preparation that method by experiment in vitro detects two kinds of forms of the present invention is very low to the toxicity of mdck cell.The inhibitory action and the virus control group that mdck cell are infected H1N1, H3N2 virus compare, notable difference is arranged, mdck cell is infected the inhibitory action and the amantadine group of H1N1, H3N2 virus and relatively do not have significant difference, show H1N1, H3N2 virus are had than the obvious suppression effect, half-inhibition concentration IC50 is respectively (5..34mg/l, 7.48mg/l), therapeutic index TI is respectively (14.46,10.32), apparently higher than the TI (7.95,7.44) of positive control amantadine.The experiment in vitro result shows has the obvious suppression effect to H1N1, H3N2 influenza virus, and its toxicity is lower than amantadine.
Adopt the Chinese medicine composition of Rhizoma Paridis, Herba Hyperici perforati extract preparation, make targeting, target spot clearer and more definite, outstanding effect is concentrated one's efforts grand.The treatment influenza belongs to the disease combination, invades the criminal's of defending lung at epidemic disease due to heat pathogen virus, and the heat-clearing and toxic substances removing expelling pathogenic factors from the exterior protects lung and defends, both in emergency, also for getting cause of disease Zhi Qiben.
Following experimental example and embodiment do further explanation to the present invention, but do not constitute restriction of the present invention.
The gram of Rhizoma Paridis described in following experimental example sense drop pill is the prepared product of embodiment 1 method.
Experimental example 1 clinical experiment
The case history source:
The outpatient service prescription on individual diagnosis person who generates heat in 48 hours is divided into treatment group and matched group at random.
136 examples are organized in treatment, male 64 examples, women 72 examples; Minimum 11 years old of age, maximum 70 years old; 37.5～38 ℃ of body temperature, 58 examples; 38.1～39 ℃, 64 examples; 39.1～40 ℃; 14 examples.
Matched group 136 examples, male 67 examples, women 69 examples; Minimum 13 years old of age, maximum 69 years old; 37.5～38 ℃ of body temperature, 56 examples; 39.1～40 ℃, 12 examples.
Two groups of case baseline data are learned processing by statistics, there was no significant difference, (P〉0.05).
1, clinical manifestation
1.1 epidemiological history
A large amount of heat generation upper respiratory tract infection patients or fever clinic appear season in influenza, emergency treatment heat generation upper respiratory tract infection patient obviously increases.
1.2 clinical primary symptom and lab testing
Primary symptom: acute onset, symptoms such as heating, fear of cold, pharyngalgia, dizziness, headache, systemic pain, cough, red tongue, yellow fur, floating and rapid pulse.
Lab testing: the not high or attenuating of peripheral hemogram total white blood cells, lymphocyte increases relatively.
Except other febrile diseases.
Western medicine diagnose is an influenza; Chinese medical discrimination belongs to epidemic disease due to heat pathogen virus and invades the criminal's of defending lung person.
1.3 criterion of therapeutical effect
Curative effect judging standard is formulated with reference to " new Chinese medicine treatment clinical research guideline ".
Clinical recovery: treat 3 days normal with interior temperature recovery, clinical symptoms, sign disappear;
Produce effects: treat in 3 days, body temperature is normal substantially, and clinical symptoms, sign are obviously improved;
Effectively: treated 2 days, body temperature descends, and clinical symptoms, sign all take a favorable turn;
Invalid: treated 3 days, body temperature does not fall or raises, and clinical symptoms does not have obvious improvement, even increase the weight of.
1.4 data processing method
Measurement data adopts the t check, and ranked data adopt Ridit to analyze.
1.5 Therapeutic Method
Treatment group: adopt the treatment of Rhizoma Paridis gram sense drop pill.Drop pill, every
50mg, each
0.5g, every day 3 times, buccal or warm water delivery service after meal.The 15g/ crude drug/everyone/day.
Matched group: give the amantadine hydrochloride sheet, (the accurate word of traditional Chinese medicines: H21020714, manufacturer: Dongbei Pharmaceutical General Factory, main component are amantadine hydrochloride) 0.1g/ sheet, 1 0.3g, 1 day 3 times.
Annotate: treatment group, matched group body temperature suitably give Physical temperature-lowering 39.1～40 ℃ of persons.
2, therapeutic outcome
Relatively there were significant differences for treatment group and matched group curative effect, and treatment group curative effect is better than matched group.See two groups of curative effect comparision tables 1.
Table 1 liang group Comparison of therapeutic table [n (%)]
Annotate: two groups of Comparison of therapeutic, analyze u=5.545, P＜0.01 through Ridit.
The result: 136 routine influenza patients use Rhizoma Paridis gram sense prescription and exempted to fry in shallow oil granule therapy 3 days, cure 82 examples, produce effects 27 examples, and 23 examples that take a turn for the better, invalid 4 examples, total effective rate is 96.7%.
Conclusion: it is evident in efficacy that Rhizoma Paridis gram sense prescription exempts to fry in shallow oil the granule therapy influenza.
Experimental example 2 acute toxicity tests
Give mice Rhizoma Paridis gram sense drop pill 5g/kg and irritate stomach, mice does not occur poisoning and is dead, so can't measure LD50.
Animal activity reacts as usual freely behind the Rhizoma Paridis gram sense drop pill gastric infusion, and viewing duration mice hair growth is normal, eupnea, and the skin glossiness is good, ingests, to take the photograph water normal, large and small just normal.Mice body constitution amount increases in the 14d, is increased to (32.72 ± 1.62) g by (20.13 ± 0.67) g before the test, and the 48h animal does not have death, all healthy survival of 2 week back all animals.Mice was put to death in the cervical vertebra dislocation when experiment finished, and dissected back perusal main organs color and morphological change, and main organs such as the heart, liver, spleen, lung, kidney, stomach, intestinal there is no abnormal change as a result.
Experimental result shows: give mice Rhizoma Paridis gram sense drop pill 16g/kg (being equivalent to crude drug amount 125g/kg) (40% suspension 0.4ml/10gig by the maximum tolerated dose method, administration in one day 2 times), mice there is not the overt toxicity effect, behave approximately 583 times of clinical usual amounts of its maximum dosage-feeding show that this medicine is safe and reliable.
Experimental example 3 external resisiting influenza virus tests
1, Rhizoma Paridis gram sense drop pill is to the toxic action of mdck cell
Adopt the cytopathy political reform to detect the toxicity of Rhizoma Paridis gram sense drop pill to mdck cell in conjunction with mtt assay, experimental result sees Table 2.The maximal non-toxic concentration of Rhizoma Paridis gram sense drop pill is (28.33mg/l), and median lethal concentration is (77.25mg/l); The maximal non-toxic concentration of amantadine is (11.34mg/l), and median lethal concentration is (34.53mg/l).The toxicity of Rhizoma Paridis gram sense drop pill is starkly lower than the toxicity of positive control medicine amantadine.
(table 2 Rhizoma Paridis gram sense drop pill is to the toxic action of mdck cell)
| Group | TC50 | TC0 |
| Rhizoma Paridis gram sense drop pill | 77.25mg/l | 28.33mg/l |
| Amantadine | 34.53mg/l | 11.34mg/l |
2, the Rhizoma Paridis gram is felt drop pill inhibitory action to H1N1 in MDCK
Adopt the CPE method to detect the inhibitory action of Rhizoma Paridis gram sense drop pill to H1N1 in conjunction with mtt assay, experimental result sees Table 3.According to absorbance 0D value, calculate each dosage suppression ratio to influenza virus H1N1 in mdck cell, adopt Reed-Muench method calculation of half inhibitory concentration IC50, and feel the TC50 value of drop pill according to the Rhizoma Paridis gram of previous calculations gained, calculate therapeutic index TI, the results are shown in Table 4.
(table 3 Rhizoma Paridis gram sense drop pill is to the inhibitory action of H1N1)
| Grouping | The A value |
| The cell contrast | 2.34±0.03 |
| Virus control | 0.51±0.03 |
| Rhizoma Paridis single medicinal material drop pill 0.125g/L | 0.74±0.20*，* |
| Herba Hyperici perforati single medicinal material drop pill 0.125g/L | 0.93±0.24*，* |
| Rhizoma Paridis gram sense drop pill 0.125g/L | 1.68±0.07*，*，# |
| Rhizoma Paridis gram sense drop pill 0.25g/L | 1.91±0.01*，*，# |
| Amantadine 0.0125g/L | 1.43±0.13*，* |
| Amantadine 0.025g/L | 1.83±0.01*，* |
| Amantadine 0.05g/L | 1.97±0.05*，* |
| Amantadine 0.1g/L | 2.15±0.045*，* |
Compare * P＜0.05 with sick with cell matched group, virus control group, amantadine group respectively; #P〉0.05
(table 4 Rhizoma Paridis gram sense drop pill is to the inhibitory action of H1N1)
| Grouping | TC50 | IC50 | TI |
| Rhizoma Paridis gram sense drop pill | 77.25mg/l | 5..34mg/l | 14.46 |
| Amantadine | 34.53mg/l | 4.34mg/l | 7.95 |
3, the Rhizoma Paridis gram is felt drop pill inhibitory action to H3N2 in MDCK
Adopt the CPE method to detect the inhibitory action of Rhizoma Paridis gram sense drop pill to H3N2 in conjunction with mtt assay, experimental result sees Table 5.According to absorbance 0D value, calculate each dosage suppression ratio to influenza virus H3N2 in mdck cell, adopt Reed-Muench method calculation of half inhibitory concentration IC50, and restrain the TC50 value of feeling drop pill according to the building of previous calculations gained, calculate therapeutic index TI.
(table 5 Rhizoma Paridis gram sense drop pill is to the inhibitory action of H3N2)
| Grouping | A |
| The cell contrast | 2.56±0.01 |
| Virus control | 0.39±0.03 |
| Rhizoma Paridis single medicinal material drop pill 0.125g/L | 0.74±0.04*，*，* |
| Herba Hyperici perforati single medicinal material drop pill 0.125g/L | 1.11±0.10*，*，* |
| Rhizoma Paridis gram sense drop pill 0.125g/L | 1.57±0.03*，*，* |
| Rhizoma Paridis gram sense drop pill 0.25g/L | 1.84±0.05*，*，# |
| Amantadine 0.0125g/L | 1.65±0.03*，* |
| Amantadine 0.025g/L | 1.73±0.08*，* |
| Amantadine 0.05g/L | 1.78±0.16*，* |
| Amantadine 0.1g/L | 1.97±0.09*，* |
Compare * with sick with cell matched group, virus control group, amantadine group respectively
Resisiting influenza virus in experimental example 4 bodies
Each organizes the observation of experiment mice behavior: normal control group mice spirit is good, physical agility, and hair is glossy, breathes normally, and diet is normal, body weight natural increase.
After FM1 infection model group, Chinese drug-treated group, the amantadine group, mouse infection virus obvious abnormal symptom do not occur in back two days, the 3rd day begins to occur rapid breathing based on ventral breathing, it is unable to be slow in action, unite roll up, fear of cold is afraid of cold, the hair tarnish, diet performance such as obviously reduce, become thin.Virus control group, Rhizoma Paridis gram sense drop pill group began to occur dead in low dose of the 7th day, and the death time concentrates on the 7th, eight, the Ninth Heaven; Rhizoma Paridis gram sense drop pill group heavy dose, the large and small dosage of amantadine group began to occur dead on the 8th day, and the death time concentrates on the 8th, nine, ten day; In the Rhizoma Paridis gram sense drop pill group in dosage, the amantadine group dosage began to occur dead on the 9th day, the death time concentrates and appears at the 9th, ten, 11 day.After the 11 day, each is organized mice and no longer includes death, and state begins to take a turn for the better, movable increasing, and diet begins to recover, but still normal matched group is low.
Following embodiment all can realize the described effect of above-mentioned experimental example
The specific embodiment
Embodiment 1: drop pill
Prescription: Rhizoma Paridis 900g, Herba Hyperici perforati 600g
The Rhizoma Paridis medical material was measured reflux, extract, 2 hours with 10 times for the first time with 70% ethanol extraction twice, extracted 1.5h with 8 times of amounts (being weight ratio) for the second time; Extracting solution filters, and merges.With the centrifugal 30min of the speed of 2500rpm, get supernatant, and collect residue; Supernatant adopts the AB-8 resin, last sample concentration 0.2g/ml, and absorption flow velocity 2BV/h, washing volume 5BV, 30% ethanol elution 5BV, eluant are 70% ethanol, the eluant consumption is 3BV/h for the 5.5BV elution flow rate; 70% eluent is merged with residue, reclaim ethanol, vacuum drying.
Herba Hyperici perforati is with 80% ethanol extraction 2 times, each 2.0 hours, 10 times of amounts; Extracting solution filters, and merges.With the centrifugal 30min of the speed of 2500rpm, get supernatant, and collect residue; Supernatant adopts HPD-100 resin and D-101 resin, last sample concentration 0.15g/ml, and absorption flow velocity 2BV/h, washing volume 4BV, 20% ethanol elution 5BV, eluant are 60% ethanol, and the eluant consumption is 5BV, and elution flow rate is 3BV/h; 60% eluent is merged with residue, reclaim ethanol, vacuum drying.
Above-mentioned Rhizoma Paridis extract, Herba Hyperici perforati extract are merged, pulverize and be fine powder.Join among the molten matrix PEG4000:6000=3:1 (70 ℃ of melt temperatures), the ratio of its Chinese medicine and substrate is more than the 1:0.8.Condensing agent is a methyl-silicone oil-50; Drip system 65～75 ℃ of temperature (being 75 ℃), drip, cooling column length 50cm, condensation temperature: ice-water bath apart from 6cm.The drop pill of preparation is 3000.Drop pill, every
50mg, each.
0.5g, every day 3 times, buccal or warm water delivery service after meal.
Function: heat-clearing and toxic substances removing.Main syndrome (indication): be mainly used in by epidemic disease due to heat pathogen virus and invade the traditional Chinese medical science " influenza " due to the human body (clinically mainly showing as: anxious hyperpyrexia, the systemic pain, weak of rising, companion's symptom such as slightly cough, cough up phlegm); The influenza (influenza is called for short influenza) that modern medicine is alleged belongs to this category, can be by this disease Coryza Treated by Syndrome Differentiation.
Embodiment 2
Prescription: Rhizoma Paridis 1000g, Herba Hyperici perforati 600g
The Rhizoma Paridis medical material was measured reflux, extract, 2 hours with 11 times for the first time with 70% ethanol extraction twice, extracted 1.5h with 9 times of amounts (being weight ratio) for the second time; Extracting solution filters, and merges.With the centrifugal 30min of the speed of 2500rpm, get supernatant, and collect residue; Supernatant adopts the AB-8 resin, last sample concentration 0.2g/ml, and absorption flow velocity 2BV/h, washing volume 5BV, 30% ethanol elution 5BV, eluant are 70% ethanol, the eluant consumption is 3BV/h for the 5.5BV elution flow rate; 70% eluent is merged with residue, reclaim ethanol, vacuum drying.
Herba Hyperici perforati is with 80% ethanol extraction 2 times, each 2.0 hours, 10 times of amounts; Extracting solution filters, and merges.With the centrifugal 30min of the speed of 2500rpm, get supernatant, and collect residue; Supernatant adopts HPD-100 resin and D-101 resin, last sample concentration 0.15g/ml, and absorption flow velocity 2BV/h, washing volume 4BV, 20% ethanol elution 5BV, eluant are 60% ethanol, and the eluant consumption is 5BV, and elution flow rate is 3BV/h; 60% eluent is merged with residue, reclaim ethanol, vacuum drying.
Above-mentioned Rhizoma Paridis extract, Herba Hyperici perforati extract are merged, pulverize and be fine powder.Join among the molten matrix PEG4000:6000=4:1 (70 ℃ of melt temperatures), the ratio of its Chinese medicine and substrate is more than the 1:0.8.Condensing agent is a methyl-silicone oil-50; Drip system 65～75 ℃ of temperature (being 75 ℃), drip, cooling column length 50cm, condensation temperature: ice-water bath apart from 6cm.
Embodiment 3
Rhizoma Paridis 900g, Herba Hyperici perforati 600g;
Crude drug decocts with water 3 times, and each water consumption is 8 times (weight ratios) of medical material amount, extracts 1.5 hours at every turn, and merge extractive liquid, filters, and promptly gets extracting solution; Said extracted liquid is filtered, filtrate is by macroporous resin, and with the ethanol elution of 20% following concentration, eluent is abandoned or adopted earlier, reuse adds 5 times of eluting of 70% ethanol, the collection eluent, decompression recycling ethanol gets the purification extracting solution to there not being the alcohol flavor, dry, pulverize to fine powder, join among the molten matrix PEG4000:6000=3:1 (70 ℃ of melt temperatures), the ratio of its mesostroma and medicine is 1:1.Condensing agent is a methyl-silicone oil-50; Drip system 65～75 ℃ of temperature (being 75 ℃), drip, cooling column length 50cm, condensation temperature: ice-water bath apart from 6cm.
The present embodiment drop pill in MDCK to the inhibitory action of H1N1
Adopt the CPE method to detect the inhibitory action of drop pill to H1N1 in conjunction with mtt assay, experimental result sees the following form.
Drop pill is to the inhibitory action of H1N1
| Grouping | The A value |
| The cell contrast | 2.32±0.03 |
| Virus control | 0.50±0.03 |
| Embodiment drop pill 0.125g/L | 1.55±0.07*，*，# |
| Amantadine 0.0125g/L | 1.43±0.12*，* |
Compare * P＜0.05 with sick with cell matched group, virus control group, amantadine group respectively; #P〉0.05
Embodiment 4
Rhizoma Paridis extract 90g, Herba Hyperici perforati extract 60g; The total amount of Rhizoma Paridis saponin I, II is greater than 20% in the Rhizoma Paridis extract; Total saponin content is greater than 60%; The content of hypericin is greater than 0.4% in the Herba Hyperici perforati extract, and general flavone content is greater than 20%; Make tablet through conventional technology.
Embodiment 5
Rhizoma Paridis extract 80g, Herba Hyperici perforati extract 60g; The total amount of Rhizoma Paridis saponin I, II is greater than 15% in the Rhizoma Paridis extract; Total saponin content is greater than 50%; The content of hypericin is greater than 0.3% in the Herba Hyperici perforati extract, and general flavone content is greater than 15%; Make capsule through conventional technology.
Embodiment 6
Rhizoma Paridis extract 100g, Herba Hyperici perforati extract 60g; Above-mentioned Rhizoma Paridis extract, Herba Hyperici perforati extract are merged, pulverize and be fine powder.Join among the molten matrix PEG4000:6000=3:1 (70 ℃ of melt temperatures), the ratio of its Chinese medicine and substrate is more than the 1:0.8.Condensing agent is a methyl-silicone oil-50; Drip system 65～75 ℃ of temperature (being 75 ℃), drip, cooling column length 50cm, condensation temperature: ice-water bath apart from 6cm.
Embodiment 7
Rhizoma Paridis 1000g, Herba Hyperici perforati 600g.
Add 60% ethanol extraction 2 times, each ethanol consumption is 5 times (weight ratios) of medical material amount, extracts 1.5 hours at every turn, and merge extractive liquid, reclaims ethanol to there not being the alcohol flavor, promptly gets extracting solution, makes capsule through conventional technology.
Embodiment 8
Rhizoma Paridis water extract 100g, Herba Hyperici perforati alcohol extract 60g; Above-mentioned Rhizoma Paridis extract, Herba Hyperici perforati extract are merged, pulverize and be fine powder.Join among the molten matrix PEG4000:6000=3:1 (70 ℃ of melt temperatures), the ratio of its Chinese medicine and substrate is more than the 1:0.8.Condensing agent is a methyl-silicone oil-50; Drip system 65～75 ℃ of temperature (being 75 ℃), drip, cooling column length 50cm, condensation temperature: ice-water bath apart from 6cm.
Embodiment 9
Rhizoma Paridis water was carried the refining thing 90g of post, Herba Hyperici perforati alcohol extract 60g; Above-mentioned Rhizoma Paridis extract, Herba Hyperici perforati extract are merged, pulverize and be fine powder.Join molten matrix PEG4000: agent is a methyl-silicone oil-50; Drip system 65～75 ℃ of temperature (being 75 ℃), drip, cooling column length 50cm, condensation temperature: ice-water bath apart from 6cm.
Embodiment 10
Rhizoma Paridis water was carried the refining thing 90g of post, and the refining thing 60g of post is crossed in the Herba Hyperici perforati alcohol extraction; Above-mentioned Rhizoma Paridis extract, Herba Hyperici perforati extract are merged, pulverize and be fine powder, make tablet through conventional technology.
Claims (10)
1. treat grippal Chinese medicine composition for one kind, it is characterized in that making by the raw material of following weight ratio:
Rhizoma Paridis 3-15 weight portion, Herba Hyperici perforati 3-9 weight portion.
2. Chinese medicine composition as claimed in claim 1 is characterized in that being made by the raw material of following weight ratio:
Rhizoma Paridis 8-10 weight portion, Herba Hyperici perforati 5-8 weight portion.
3. Chinese medicine composition as claimed in claim 2 is characterized in that being made by the raw material of following weight ratio:
Rhizoma Paridis 9 weight portions, Herba Hyperici perforati 6 weight portions.
4. treat grippal Chinese medicine composition for one kind, it is characterized in that making by the raw material of following weight ratio:
Rhizoma Paridis extract 3-15 weight portion, Herba Hyperici perforati extract 3-9 weight portion;
Wherein in the Rhizoma Paridis extract total amount of Rhizoma Paridis saponin I, II greater than 15%; Total saponin content is greater than 50%;
Wherein the content of hypericin is greater than 0.3% in the Herba Hyperici perforati extract, and general flavone content is greater than 15%.
5. Chinese medicine composition as claimed in claim 4 is characterized in that being made by the raw material of following weight ratio:
Rhizoma Paridis extract 8-10 weight portion, Herba Hyperici perforati extract 5-8 weight portion.
6. Chinese medicine composition as claimed in claim 5 is characterized in that being made by the raw material of following weight ratio:
Rhizoma Paridis extract 9 weight portions, Herba Hyperici perforati extract 6 weight portions.
7. as described any one Chinese medicine composition of one of claim 4-6, it is characterized in that:
Rhizoma Paridis extract is that alcohol extraction is crossed the refining thing of post, water and carried in post refining thing, ethanol extract or the water extract any one;
Herba Hyperici perforati extract is that alcohol extraction is crossed the refining thing of post, water and carried in post refining thing, ethanol extract or the water extract any one.
8. as the preparation method of one of claim 4-6 described any one Chinese medicine composition, it is characterized in that the preparation method of drop pill is:
The weight ratio of substrate and medicine is more than or equal to 0.8, and substrate is PEG4000: 6000=2-4: 1; Melt temperature 65-75 ℃; Condensing agent is a methyl-silicone oil-50; Drip 65～75 ℃ of system temperature, drip, cooling column length 50cm, condensation temperature: ice-water bath apart from 6cm.
9. as the application of described any one Chinese medicine composition of one of claim 1-6 in the anti-H1N1 virus medicine of preparation.
10. as the application of described any one Chinese medicine composition of one of claim 1-6 in the anti-H3N2 virus drugs of preparation.
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| CN1813918A (en) * | 2005-12-08 | 2006-08-09 | 华南农业大学 | Chinese medicine composition for preventing avian flu |
| CN1857240A (en) * | 2006-04-06 | 2006-11-08 | 中国农业科学院兰州畜牧与兽药研究所 | Application of hypericin in preparing RNA virus resisting medicine |
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| CN1813918A (en) * | 2005-12-08 | 2006-08-09 | 华南农业大学 | Chinese medicine composition for preventing avian flu |
| CN1857240A (en) * | 2006-04-06 | 2006-11-08 | 中国农业科学院兰州畜牧与兽药研究所 | Application of hypericin in preparing RNA virus resisting medicine |
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