CN104524284A - Medicine for preventing and treating flu - Google Patents

Medicine for preventing and treating flu Download PDF

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Publication number
CN104524284A
CN104524284A CN201410807420.0A CN201410807420A CN104524284A CN 104524284 A CN104524284 A CN 104524284A CN 201410807420 A CN201410807420 A CN 201410807420A CN 104524284 A CN104524284 A CN 104524284A
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herba
medicine
folium
rhizoma
taenia
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顾�卓
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    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/32Burseraceae (Frankincense family)
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    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284Atractylodes
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    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/532Agastache, e.g. giant hyssop
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    • A61K36/60Moraceae (Mulberry family), e.g. breadfruit or fig
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Abstract

The invention provides a medicine for preventing and treating flu. The medicine consists of the following crude medicines: frankincense, bamboo shavings, rhizoma atractylodes, radix pseudostellariae, agastache rugosus, rhizoma dryopteris crassirhizomae, ephedra, cordate houttuynia, dindygulen peperomia herb, arundina graminifolia, eleusine indica, Suchow mosla herb, radix paeoniae alba, loranthus parasiticus, aster ageratoides, cypress fruit, nakedflower beautyberry branchlet and leaf, and folium mori. The medicine for preventing and treating flu disclosed by the invention has the characteristics of low side effect, rich medicine source, low cost and action targets, and the medicine is unique in advantage and broad in development prospect.

Description

Prevent and treat the medicine of influenza
Technical field
The present invention relates to technical field of Chinese medicine, particularly relating to the medicine for preventing and treating influenza.
Background technology
Influenza is the Acute respiratory infectious disease because influenza virus causes, and being called for short " influenza ", is one of current serious important diseases affecting human health.Have the advantages that sickness rate is high, infectiousness is high, death toll is many.Be no matter the propagation of popular, the bird flu virus of SARS in 2003, or the whole world of swine flu epidemic situation in 2009 is popular on a large scale, all causes huge harm to the mankind and society.
Because influenza virus easily morphs, chemicals and influenza virus vaccine is made to be difficult to play optimal treatment and preventive effect.To constantly bring forth new ideas in the practice that the traditional Chinese medical science is prevented and treated in influenza method, accumulate experience, played advantage.Influenza, the traditional Chinese medical science, also known as influenza, belongs to the category such as motherland's medical science " epidemic disease ", " pestilence ", " pathogenic wind-warm ", be by time row pathogenic factor and a kind of fever caused by exogenous pathogenic factors of causing of epidemic pathogenic factor.It shows as fear of cold heating, pharyngalgia, systemic pain, weak, the few expectorant of cough, or companion's nausea and vomiting, abdominal distention or constipation, red tongue or tongue tip side of red, yellow and thin fur, floating and rapid pulse or stringy and rapid pulse.Severe one General Symptoms weight, high heat, tachypnea of panting is obvious.Influenza early just has the description of " heterogeneous dye is easy " in ancient times, from B.C. Huangdi's Internal Classics to Eastern Han Dynasty's Zhang Zhongjing " Treatise on Febrile and Miscellaneous Disease ", Ming Dynasty Wu again can " pestilence opinion " to arrive Qing Dynasty's Wu Ju Tong " Wenbing Tiaobian, Detailed Analysis of Epidemic Warm Diseases " more all on the books.
Motherland's medical science is early on the books in the preventing and treating of influenza, and have accumulated rich experience, and advantage is comparatively obvious, is mainly manifested in: 1, resources of Chinese medicinal herb is in the Nature, and medicine source is extensive, to human non-toxic or toxicity and untoward reaction less, and cheap.2, resisting pathogenic microbes spectrum is wide, and particularly a part of Chinese herbal medicine wherein not only has broad-spectrum disease resistance toxic action, and has broad-spectrum antibacterial action.This with only have the Western medicine of antivirus action and only have the antibiotic of antibacterial action far different.3, in antiviral and antibacterial action, pathogenic microorganism to Chinese herbal medicine particularly compound recipe not easily produce drug resistance.And also show synergism between some Chinese herbal medicine.4, there is most of Chinese herbal medicine of antiviral, antibacterial action, also have the effect of conditioner body immunity function.
Adopt herbal control influenza virus to have few side effects, medicine source is enriched, cheap, the feature that action target spot is many, and have unique advantage and vast potential for future development, the present invention proposes a kind of medicine for preventing and treating influenza on the basis of theory of Chinese medical science.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of medicine for preventing and treating influenza, its few side effects, and medicine source is enriched, cheap, the feature that action target spot is many, has unique advantage and vast potential for future development.
For solving the problems of the technologies described above, the invention provides a kind of medicine for preventing and treating influenza, its crude drug comprises Olibanum, Caulis Bambusae In Taenia, Rhizoma Atractylodis, Radix Pseudostellariae, Herba Pogostemonis, Rhizoma Dryopteris Crassirhizomatis, Herba Ephedrae, Herba Houttuyniae, Herba Peperomiae Dindygulensis, Herba Murdanniae Divergentis, Herba Eleusines Indicae, Herba Moslae Soochowensis, the Radix Paeoniae Alba, Herba Taxilli, Herba Asteris Ageratoidis, Strobilus Cupressi, Folium et Ramulus Callicarpae nudiflorae and Folium Mori.
In described medicine, the weight of each crude drug is respectively Olibanum 10g ~ 30g, Caulis Bambusae In Taenia 20g ~ 40g, Rhizoma Atractylodis 10g ~ 30g, Radix Pseudostellariae 30g ~ 50g, Herba Pogostemonis 10g ~ 30g, Rhizoma Dryopteris Crassirhizomatis 10g ~ 30g, Herba Ephedrae 20g ~ 40g, Herba Houttuyniae 10g ~ 30g, Herba Peperomiae Dindygulensis 10g ~ 30g, Herba Murdanniae Divergentis 20g ~ 40g, Herba Eleusines Indicae 10g ~ 30g, Herba Moslae Soochowensis 10g ~ 30g, Radix Paeoniae Alba 20g ~ 40g, Herba Taxilli 10g ~ 30g, Herba Asteris Ageratoidis 20g ~ 40g, Strobilus Cupressi 10g ~ 30g, Folium et Ramulus Callicarpae nudiflorae 10g ~ 30g and Folium Mori 10g ~ 30g.
In described medicine, the weight of each crude drug also can be respectively Olibanum 10g ~ 20g, Caulis Bambusae In Taenia 20g ~ 30g, Rhizoma Atractylodis 10g ~ 20g, Radix Pseudostellariae 30g ~ 40g, Herba Pogostemonis 10g ~ 20g, Rhizoma Dryopteris Crassirhizomatis 10g ~ 20g, Herba Ephedrae 20g ~ 30g, Herba Houttuyniae 10g ~ 20g, Herba Peperomiae Dindygulensis 10g ~ 20g, Herba Murdanniae Divergentis 20g ~ 40g, Herba Eleusines Indicae 10g ~ 30g, Herba Moslae Soochowensis 10g ~ 30g, Radix Paeoniae Alba 20g ~ 40g, Herba Taxilli 10g ~ 30g, Herba Asteris Ageratoidis 20g ~ 40g, Strobilus Cupressi 10g ~ 30g, Folium et Ramulus Callicarpae nudiflorae 10g ~ 30g and Folium Mori 10g ~ 30g.
In described medicine, the weight of each crude drug also can be respectively Olibanum 10g ~ 30g, Caulis Bambusae In Taenia 20g ~ 40g, Rhizoma Atractylodis 10g ~ 30g, Radix Pseudostellariae 30g ~ 50g, Herba Pogostemonis 10g ~ 30g, Rhizoma Dryopteris Crassirhizomatis 10g ~ 30g, Herba Ephedrae 20g ~ 40g, Herba Houttuyniae 10g ~ 30g, Herba Peperomiae Dindygulensis 10g ~ 30g, Herba Murdanniae Divergentis 30g ~ 40g, Herba Eleusines Indicae 20g ~ 30g, Herba Moslae Soochowensis 20g ~ 30g, Radix Paeoniae Alba 30g ~ 40g, Herba Taxilli 20g ~ 30g, Herba Asteris Ageratoidis 30g ~ 40g, Strobilus Cupressi 20g ~ 30g, Folium et Ramulus Callicarpae nudiflorae 20g ~ 30g and Folium Mori 20g ~ 30g.
In described medicine, the weight of each crude drug also can be respectively Olibanum 20g, Caulis Bambusae In Taenia 30g, Rhizoma Atractylodis 20g, Radix Pseudostellariae 40g, Herba Pogostemonis 20g, Rhizoma Dryopteris Crassirhizomatis 20g, Herba Ephedrae 30g, Herba Houttuyniae 20g, Herba Peperomiae Dindygulensis 20g, Herba Murdanniae Divergentis 30g, Herba Eleusines Indicae 20g, Herba Moslae Soochowensis 20g, Radix Paeoniae Alba 30g, Herba Taxilli 20g, Herba Asteris Ageratoidis 30g, Strobilus Cupressi 20g, Folium et Ramulus Callicarpae nudiflorae 20g and Folium Mori 20g.
The medicine preventing and treating influenza provided by the invention can be prepared into any dosage form for oral administration, as tablet, granule, capsule, oral liquid, syrup etc., is preferably prepared into granule and capsule.
Present invention also offers the preparation method of said medicine, it comprises:
The first step, first by Olibanum, Rhizoma Atractylodis, Radix Pseudostellariae, Herba Ephedrae, Herba Houttuyniae, Herba Eleusines Indicae, Herba Moslae Soochowensis, Herba Taxilli is cut into coarse granule respectively, mix, then the ethanol that determining alcohol is 70% ~ 80% is put into, ethanol did not have above-mentioned raw materials medicine mixture, soak more than 2 hours, the determining alcohol adding 8 times amount accounting for above-mentioned raw materials medicine mixture gross mass be subsequently 70% ~ 80% alcohol heating reflux extract 2 hours, cooling, filter, the determining alcohol again adding 6 times amount accounting for above-mentioned raw materials medicine mixture gross mass in filtering residue be 70% ~ 80% alcohol heating reflux extract 2 hours, filter, the filtrate of twice filtration is mixed, obtain the first filtrate,
Second step, Caulis Bambusae In Taenia, Herba Pogostemonis, Rhizoma Dryopteris Crassirhizomatis, Herba Peperomiae Dindygulensis, Herba Murdanniae Divergentis, the Radix Paeoniae Alba, Herba Asteris Ageratoidis, Strobilus Cupressi, Folium et Ramulus Callicarpae nudiflorae and Folium Mori are cut into coarse granule respectively, mix, to account for above-mentioned raw materials medicine mixture gross mass 8 ~ 12 times amount 70% ~ 80% alcohol dipping, slowly percolation is complete, obtains percolate;
3rd step, by the first filtrate and percolate mixing, carry out coarse filtration and fine straining with filter press, it is 1.15 that fine straining liquid Three-effect energy-saving concentrator is concentrated into relative density, temperature 60 C; Concentrated solution spray drying method, feed liquor speed 6000ml/min, centrifugal speed 6000r/min, inlet temperature 120 DEG C, prepares extract powder;
4th step, adds adjuvant according to the dosage form of various needs, prepares corresponding dosage form product in extract powder prepared by the 3rd step.
When dosage form prepared by described medicine is granule; described 4th step is specially further and adds dextrin and sucrose in extract powder; the extract powder of every 100g; the addition of dextrin is 100g ~ 120g; the addition of sucrose is 120g ~ 150g; be placed in wet granulator; mix 3 ~ 8 minutes, make granule, send in vacuum drier and carry out vacuum drying; temperature of charge is 40 ~ 70 DEG C; vacuum is-0.08Mpa ~-0.12Mpa, and charging rate is 15 ~ 20L/h, and material strip transfer rate is 20 ~ 30cm/min; subpackage after dry, 5g mono-bag.
When dosage form prepared by described medicine is capsule, described 4th step is specially further and adds microcrystalline Cellulose 98g and micropowder silica gel 2g in extract powder described in every 100g, and cross 80 mesh sieve 3 times, mix homogeneously, is sub-packed in capsule, obtains final product.
Beneficial effect of the present invention:
Medicine for preventing and treating influenza provided by the invention, its few side effects, medicine source is enriched, cheap, the feature that action target spot is many, has unique advantage and vast potential for future development.
Detailed description of the invention
The invention provides a kind of medicine for preventing and treating influenza, its crude drug comprises Olibanum, Caulis Bambusae In Taenia, Rhizoma Atractylodis, Radix Pseudostellariae, Herba Pogostemonis, Rhizoma Dryopteris Crassirhizomatis, Herba Ephedrae, Herba Houttuyniae, Herba Peperomiae Dindygulensis, Herba Murdanniae Divergentis, Herba Eleusines Indicae, Herba Moslae Soochowensis, the Radix Paeoniae Alba, Herba Taxilli, Herba Asteris Ageratoidis, Strobilus Cupressi, Folium et Ramulus Callicarpae nudiflorae and Folium Mori.
Described medicine is only made up of above-mentioned raw materials medicine further.
In described medicine, the weight of each crude drug is respectively Olibanum 10g ~ 30g, Caulis Bambusae In Taenia 20g ~ 40g, Rhizoma Atractylodis 10g ~ 30g, Radix Pseudostellariae 30g ~ 50g, Herba Pogostemonis 10g ~ 30g, Rhizoma Dryopteris Crassirhizomatis 10g ~ 30g, Herba Ephedrae 20g ~ 40g, Herba Houttuyniae 10g ~ 30g, Herba Peperomiae Dindygulensis 10g ~ 30g, Herba Murdanniae Divergentis 20g ~ 40g, Herba Eleusines Indicae 10g ~ 30g, Herba Moslae Soochowensis 10g ~ 30g, Radix Paeoniae Alba 20g ~ 40g, Herba Taxilli 10g ~ 30g, Herba Asteris Ageratoidis 20g ~ 40g, Strobilus Cupressi 10g ~ 30g, Folium et Ramulus Callicarpae nudiflorae 10g ~ 30g and Folium Mori 10g ~ 30g.
In described medicine, the weight of each crude drug also can be respectively Olibanum 10g ~ 20g, Caulis Bambusae In Taenia 20g ~ 30g, Rhizoma Atractylodis 10g ~ 20g, Radix Pseudostellariae 30g ~ 40g, Herba Pogostemonis 10g ~ 20g, Rhizoma Dryopteris Crassirhizomatis 10g ~ 20g, Herba Ephedrae 20g ~ 30g, Herba Houttuyniae 10g ~ 20g, Herba Peperomiae Dindygulensis 10g ~ 20g, Herba Murdanniae Divergentis 20g ~ 40g, Herba Eleusines Indicae 10g ~ 30g, Herba Moslae Soochowensis 10g ~ 30g, Radix Paeoniae Alba 20g ~ 40g, Herba Taxilli 10g ~ 30g, Herba Asteris Ageratoidis 20g ~ 40g, Strobilus Cupressi 10g ~ 30g, Folium et Ramulus Callicarpae nudiflorae 10g ~ 30g and Folium Mori 10g ~ 30g.
In described medicine, the weight of each crude drug also can be respectively Olibanum 10g ~ 30g, Caulis Bambusae In Taenia 20g ~ 40g, Rhizoma Atractylodis 10g ~ 30g, Radix Pseudostellariae 30g ~ 50g, Herba Pogostemonis 10g ~ 30g, Rhizoma Dryopteris Crassirhizomatis 10g ~ 30g, Herba Ephedrae 20g ~ 40g, Herba Houttuyniae 10g ~ 30g, Herba Peperomiae Dindygulensis 10g ~ 30g, Herba Murdanniae Divergentis 30g ~ 40g, Herba Eleusines Indicae 20g ~ 30g, Herba Moslae Soochowensis 20g ~ 30g, Radix Paeoniae Alba 30g ~ 40g, Herba Taxilli 20g ~ 30g, Herba Asteris Ageratoidis 30g ~ 40g, Strobilus Cupressi 20g ~ 30g, Folium et Ramulus Callicarpae nudiflorae 20g ~ 30g and Folium Mori 20g ~ 30g.
In described medicine, the weight of each crude drug also can be respectively Olibanum 20g, Caulis Bambusae In Taenia 30g, Rhizoma Atractylodis 20g, Radix Pseudostellariae 40g, Herba Pogostemonis 20g, Rhizoma Dryopteris Crassirhizomatis 20g, Herba Ephedrae 30g, Herba Houttuyniae 20g, Herba Peperomiae Dindygulensis 20g, Herba Murdanniae Divergentis 30g, Herba Eleusines Indicae 20g, Herba Moslae Soochowensis 20g, Radix Paeoniae Alba 30g, Herba Taxilli 20g, Herba Asteris Ageratoidis 30g, Strobilus Cupressi 20g, Folium et Ramulus Callicarpae nudiflorae 20g and Folium Mori 20g.
Olibanum: acrid in the mouth, bitter, warm in nature, enter the heart, liver, spleen channel, there is regulating qi and activating blood, analgesic therapy, chase after effect of poison, cure mainly coagulation of QI-blood, trusted subordinate's pain, carbuncle pyogenic infections from tumour or sore, traumatic injury, dysmenorrhea, the cards such as postnatal blood stasis twinge.
Caulis Bambusae In Taenia: cold nature, sweet in the mouth, attaches to the lung and stomach meridians, and has removing heat-phlegm, the effect relieved restlessness and prevented vomiting, and holds the card such as expectorant, dysphoria with smothery sensation vomiting, palpitation with fear insomnia, middle wind-phlegm fan, aphasia with stiff tongue, gastropyretic vomiting, pregnancy reactions, frequent fetal movement under the arm for phlegm-heat cough, gallbladder fire.
Rhizoma Atractylodis: acrid in the mouth, hardship, warm in nature, enter spleen, stomach, Liver Channel, have drying damp and strengthening spleen, expelling wind and dampness, the effect of improving eyesight, be mainly used in the stomachache dysentery of retention of dampness in middle-JIAO, the abdominal distention pain of incoordination between the spleen and stomach, vomits indigestion and loss of appetite; The abdomen side of body distending pain, the vomiting with acid regurgitation of incoordination between the liver and stomach; And the card such as the anemofrigid-damp arthralgia of the outer strongly fragrant meridians of cold-damp.
Radix Pseudostellariae: sweet in the mouth, micro-hardship, property is put down, and enters spleen, lung meridian, has air making-up and spleen enlivening, the effect of the lung moistening and production of body fluid promoting, for the lack of appetite asthenia of deficiency-weakness of spleen-QI, deficiency of stomach-Yin, energy strengthening the spleen gas, nourishing stomach-YIN, for deficiency of the lung cough caused by dryness and cardiopalmus sleeplessness, the deficiency-heat hyperhidrosis of deficiency of vital energy Tianjin wound, energy supplementing QI for promoting the production of body fluid, controls deficiency of vital energy xeropulmonary cough, the card such as cardiopalmus sleeplessness, hyperhidrosis of deficiency of both QI and YIN.
Herba Pogostemonis: acrid in the mouth, slightly warm in nature, returns lung, spleen, stomach warp, has dispelling summer-heat from superficies of the body, effect of removing dampness to restore normal function of the stomach.For summertime flu, cold and heat are had a headache, and breast gastral cavity painful abdominal mass is vexed, and vomiting is had loose bowels, vomiting during pregnancy, nasal sinusitis, the card such as hands, tinea pedis.
Rhizoma Dryopteris Crassirhizomatis: cold nature, bitter in the mouth, returns liver, stomach warp, has heat-clearing and toxic substances removing, anthelmintic, effect of hemostasis, cures mainly and prevents the card such as influenza, abdominal pain due to worm stagnation, metrorrhagia.
Herba Ephedrae: acrid in the mouth, micro-hardship, warm in nature, enter lung, urinary bladder channel, have and send out cold inducing sweat, depressed lung-energy dispersing, the effect of inducing diuresis to remove edema, is mainly used in the exterior excess syndromes such as the fever without perspiration of affection of exogenous wind-cold; Rheumatic arthralgia pain; Pathogenic cold attacking the lung or accumulation of heat in the lung to cough with asthma QI rising in reverse order, edema, the cards such as dysuria.
Herba Houttuyniae: latin name houttuyniae herba, acrid in the mouth, cold nature, enters lung, urinary bladder channel, has heat-clearing and toxic substances removing, removing pus and relieving carbuncle, effect of inducing diuresis for treating stranguria syndrome, and for lung abscess vomiting pus, expectorant heat syndrome cough is breathed heavily, toxic-heat and blood stasis, damp-heat gonorrhoea, pyretic toxicity carbuncle sore, and snakeworm wants first-class card.
Herba Peperomiae Dindygulensis: be the herb of Piperaceae peperomia plant Herba Peperomiae Dindygulensis, acrid in the mouth, cool in nature, there is heat-clearing and toxic substances removing, blood stasis-eliminating and stagnation-dissipating, effect of diuretic, cure mainly lung-heat cough with asthma, measles, sore, malignant tumor, burn, traumatic injury, the cards such as oedema due to nephritis.
Herba Murdanniae Divergentis: be root or the herb of Commeline communis section water leaf spp plant purple back of the body Herba Pyrolae, sweet in the mouth, micro-hardship, property is put down, and have clearing away lung-heat to relieve cough, invigorating the lung and the kidney, effect of regulating menstruation, hemostasis, cures mainly cough due to lung-heat, and the deficiency of vital energy is breathed with cough, dizziness and tinnitus, fracture, spits blood.
Herba Eleusines Indicae: be root or the herb of grass family yard grass platymiscium Herba Eleusines Indicae, sweet in the mouth, light, cool in nature, there is heat-clearing and toxic substances removing, dampness removing, effect of cool the blood dissipate blood stasis, cure mainly Sunstroke heating, infantile convulsion, encephalitis b, epidemic encephalitis, jaundice, stranguria; dysuria, dysentery, has blood in stool, urticaria, the cards such as traumatic injury.
Herba Moslae Soochowensis: warm in nature, acrid in the mouth, has dispelling summer-heat from superficies of the body, and effect of regulating QI to relieve pain, cures mainly flu, heatstroke, eruptive disease, peratodynia, the cards such as laryngopharynx swelling and pain.
The Radix Paeoniae Alba: latin name paeoniae Radix Alba, bitter in the mouth, acid, cool in nature, enter liver, spleen channel, there is nourishing blood to suppress the hyperactive liver; pain relieving in slow, yin fluid astringing receives effect of antiperspirant, cures mainly the breast abdomen pain over the hypochondriac region, and dysentery is suffered from abdominal pain, spontaneous sweating; fever due to yin deficiency, menoxenia, metrorrhagia, is with inferior card, and the Radix Paeoniae Alba has good liver-protective effect.
Herba Taxilli: bitter in the mouth, sweet, property is put down, and enters liver, kidney channel, have the effect of invigorating the liver and kidney, bone and muscle strengthening, wind-damp dispelling, antiabortive unit, for the soreness of waist pain caused by deficiency of the liver and kindey, muscles and bones flaccidity is soft, the foot and knee being feeble, deficiency of the liver and kindey, essence and blood void is lost, the frequent fetal movement of liability to abortion, the cards such as waist abdomen pain.
Herba Asteris Ageratoidis: bitter in the mouth, pungent, cool in nature, have heat-clearing and toxic substances removing, the effect of the removing heat from blood that eliminates the phlegm, cures mainly cold, fever, tonsillitis, bronchitis, hepatitis, enteritis, pyretic stranguria, carbuncle furunculosis, the cards such as snake bite and insect sting.
Strobilus Cupressi: be the cone of Cupressaceae cypress Cupressus funebris Endl., bitter in the mouth, sweet, property is put down, and has and dispels the wind, and in, calm the nerves, effect of hemostasis, cures mainly cold, fever, gastralgic vomitting, irritated, insomnia, the cards such as over-strained hemoptysis.
Folium et Ramulus Callicarpae nudiflorae: be the leaf of Verenaceae Callicarpa plant Callicarpa nudiflora, puckery, micro-pungent, micro-hardship, property is put down, and have dissipating blood stasis hemostasis, effect of removing toxic substances and promoting subsidence of swelling, cures mainly hemoptysis, spits blood, has blood in stool, traumatic injury congestive edema, traumatic hemorrhage, burn due to hot liquid or fire, and sore such as to fester at the card.
Folium Mori: sweet in the mouth, bitter, cold in nature, return lung, Liver Channel, there is dispelling wind and heat pathogens, clearing away lung-heat and moistening for dryness, suppressing liver-YANG, liver heat removing and eyesight improving, effect of cooling blood for hemostasis, cure mainly anemopyretic cold, conjunctival congestion and swelling pain, wind-fire order disease, lung-heat type cough, the cards such as haematemesis warm blood.
The medicine preventing and treating influenza provided by the invention can be prepared into any dosage form for oral administration, as tablet, granule, capsule, oral liquid, syrup etc., is preferably prepared into granule and capsule.
Present invention also offers the preparation method of said medicine, it comprises:
The first step, first by Olibanum, Rhizoma Atractylodis, Radix Pseudostellariae, Herba Ephedrae, Herba Houttuyniae, Herba Eleusines Indicae, Herba Moslae Soochowensis, Herba Taxilli is cut into coarse granule respectively, mix, then the ethanol that determining alcohol is 70% ~ 80% is put into, ethanol did not have above-mentioned raw materials medicine mixture, soak more than 2 hours, the determining alcohol adding 8 times amount accounting for above-mentioned raw materials medicine mixture gross mass be subsequently 70% ~ 80% alcohol heating reflux extract 2 hours, cooling, filter, the determining alcohol again adding 6 times amount accounting for above-mentioned raw materials medicine mixture gross mass in filtering residue be 70% ~ 80% alcohol heating reflux extract 2 hours, filter, the filtrate of twice filtration is mixed, obtain the first filtrate,
Second step, Caulis Bambusae In Taenia, Herba Pogostemonis, Rhizoma Dryopteris Crassirhizomatis, Herba Peperomiae Dindygulensis, Herba Murdanniae Divergentis, the Radix Paeoniae Alba, Herba Asteris Ageratoidis, Strobilus Cupressi, Folium et Ramulus Callicarpae nudiflorae and Folium Mori are cut into coarse granule respectively, mix, to account for above-mentioned raw materials medicine mixture gross mass 8 ~ 12 times amount 70% ~ 80% alcohol dipping, slowly percolation is complete, obtains percolate;
3rd step, by the first filtrate and percolate mixing, carry out coarse filtration and fine straining with filter press, it is 1.15 that fine straining liquid Three-effect energy-saving concentrator is concentrated into relative density, temperature 60 C; Concentrated solution spray drying method, feed liquor speed 6000ml/min, centrifugal speed 6000r/min, inlet temperature 120 DEG C, prepares extract powder;
4th step, adds adjuvant according to the dosage form of various needs, prepares corresponding dosage form product in extract powder prepared by the 3rd step.
When dosage form prepared by described medicine is granule; described 4th step is specially further and adds dextrin and sucrose in extract powder; the extract powder of every 100g; the addition of dextrin is 100g ~ 120g; the addition of sucrose is 120g ~ 150g; be placed in wet granulator; mix 3 ~ 8 minutes, make granule, send in vacuum drier and carry out vacuum drying; temperature of charge is 40 ~ 70 DEG C; vacuum is-0.08Mpa ~-0.12Mpa, and charging rate is 15 ~ 20L/h, and material strip transfer rate is 20 ~ 30cm/min; subpackage after dry, 5g mono-bag.
When dosage form prepared by described medicine is capsule, described 4th step is specially further and adds microcrystalline Cellulose 98g and micropowder silica gel 2g in extract powder described in every 100g, and cross 80 mesh sieve 3 times, mix homogeneously, is sub-packed in capsule, obtains final product.
Below adopt embodiment to describe embodiments of the present invention in detail, to the present invention, how application technology means solve technical problem whereby, and the implementation procedure reaching technique effect can fully understand and implement according to this.
Granule 1
First by Olibanum 20g, Rhizoma Atractylodis 20g, Radix Pseudostellariae 40g, Herba Ephedrae 30g, Herba Houttuyniae 20g, Herba Eleusines Indicae 20g, Herba Moslae Soochowensis 20g, Herba Taxilli 20g is cut into coarse granule respectively, mix, then the ethanol that determining alcohol is 80% is put into, ethanol did not have above-mentioned raw materials medicine mixture, soak more than 2 hours, the determining alcohol adding 8 times amount accounting for above-mentioned raw materials medicine mixture gross mass be subsequently 80% alcohol heating reflux extract 2 hours, cooling, filter, the determining alcohol again adding 6 times amount accounting for above-mentioned raw materials medicine mixture gross mass in filtering residue be 80% alcohol heating reflux extract 2 hours, filter, the filtrate of twice filtration mixed, obtain the first filtrate, by Caulis Bambusae In Taenia 30g, Herba Pogostemonis 20g, Rhizoma Dryopteris Crassirhizomatis 20g, Herba Peperomiae Dindygulensis 20g, Herba Murdanniae Divergentis 30g, Radix Paeoniae Alba 30g, Herba Asteris Ageratoidis 30g, Strobilus Cupressi 20g, Folium et Ramulus Callicarpae nudiflorae 20g and Folium Mori 20g is cut into coarse granule respectively, mix, to account for above-mentioned raw materials medicine mixture gross mass 10 times amount 70% ~ 80% alcohol dipping, slowly percolation is complete, obtain percolate, by the first filtrate and percolate mixing, carry out coarse filtration and fine straining with filter press, it is 1.15 that fine straining liquid Three-effect energy-saving concentrator is concentrated into relative density, temperature 60 C, concentrated solution spray drying method, feed liquor speed 6000ml/min, centrifugal speed 6000r/min, inlet temperature 120 DEG C, prepares extract powder, dextrin and sucrose is added in extract powder, the extract powder of every 100g, the addition of dextrin is 100g, and the addition of sucrose is 120g, be placed in wet granulator, mix 5 minutes, make granule, send in vacuum drier and carry out vacuum drying, temperature of charge is 50 DEG C, vacuum is-0.1Mpa, and charging rate is 15L/h, and material strip transfer rate is 20 ~ 30cm/min, subpackage after dry, 5g mono-bag.
Granule 2
First by Olibanum 10g, Rhizoma Atractylodis 10g, Radix Pseudostellariae 30g, Herba Ephedrae 20g, Herba Houttuyniae 10g, Herba Eleusines Indicae 30g, Herba Moslae Soochowensis 30g, Herba Taxilli 30g is cut into coarse granule respectively, mix, then the ethanol that determining alcohol is 80% is put into, ethanol did not have above-mentioned raw materials medicine mixture, soak more than 2 hours, the determining alcohol adding 8 times amount accounting for above-mentioned raw materials medicine mixture gross mass be subsequently 80% alcohol heating reflux extract 2 hours, cooling, filter, the determining alcohol again adding 6 times amount accounting for above-mentioned raw materials medicine mixture gross mass in filtering residue be 80% alcohol heating reflux extract 2 hours, filter, the filtrate of twice filtration mixed, obtain the first filtrate, by Caulis Bambusae In Taenia 20g, Herba Pogostemonis 10g, Rhizoma Dryopteris Crassirhizomatis 20g, Herba Peperomiae Dindygulensis 10g, Herba Murdanniae Divergentis 40g, Radix Paeoniae Alba 40g, Herba Asteris Ageratoidis 40g, Strobilus Cupressi 30g, Folium et Ramulus Callicarpae nudiflorae 30g and Folium Mori 30g is cut into coarse granule respectively, mix, to account for above-mentioned raw materials medicine mixture gross mass 10 times amount 70% ~ 80% alcohol dipping, slowly percolation is complete, obtain percolate, by the first filtrate and percolate mixing, carry out coarse filtration and fine straining with filter press, it is 1.15 that fine straining liquid Three-effect energy-saving concentrator is concentrated into relative density, temperature 60 C, concentrated solution spray drying method, feed liquor speed 6000ml/min, centrifugal speed 6000r/min, inlet temperature 120 DEG C, prepares extract powder, dextrin and sucrose is added in extract powder, the extract powder of every 100g, the addition of dextrin is 100g, and the addition of sucrose is 120g, be placed in wet granulator, mix 5 minutes, make granule, send in vacuum drier and carry out vacuum drying, temperature of charge is 50 DEG C, vacuum is-0.1Mpa, and charging rate is 15L/h, and material strip transfer rate is 20 ~ 30cm/min, subpackage after dry, 5g mono-bag.
Capsule 1
First by Olibanum 10g, Rhizoma Atractylodis 10g, Radix Pseudostellariae 30g, Herba Ephedrae 20g, Herba Houttuyniae 10g, Herba Eleusines Indicae 30g, Herba Moslae Soochowensis 30g, Herba Taxilli 30g is cut into coarse granule respectively, mix, then the ethanol that determining alcohol is 80% is put into, ethanol did not have above-mentioned raw materials medicine mixture, soak more than 2 hours, the determining alcohol adding 8 times amount accounting for above-mentioned raw materials medicine mixture gross mass be subsequently 80% alcohol heating reflux extract 2 hours, cooling, filter, the determining alcohol again adding 6 times amount accounting for above-mentioned raw materials medicine mixture gross mass in filtering residue be 80% alcohol heating reflux extract 2 hours, filter, the filtrate of twice filtration mixed, obtain the first filtrate, by Caulis Bambusae In Taenia 20g, Herba Pogostemonis 10g, Rhizoma Dryopteris Crassirhizomatis 20g, Herba Peperomiae Dindygulensis 10g, Herba Murdanniae Divergentis 40g, Radix Paeoniae Alba 40g, , Herba Asteris Ageratoidis 40g, Strobilus Cupressi 30g, Folium et Ramulus Callicarpae nudiflorae 30g and Folium Mori 30g is cut into coarse granule respectively, mix, to account for above-mentioned raw materials medicine mixture gross mass 10 times amount 70% ~ 80% alcohol dipping, slowly percolation is complete, obtain percolate, by the first filtrate and percolate mixing, carry out coarse filtration and fine straining with filter press, it is 1.15 that fine straining liquid Three-effect energy-saving concentrator is concentrated into relative density, temperature 60 C, concentrated solution spray drying method, feed liquor speed 6000ml/min, centrifugal speed 6000r/min, inlet temperature 120 DEG C, prepare extract powder, every 100g extract powder adds microcrystalline Cellulose 98g and micropowder silica gel 2g, crosses 80 mesh sieve 3 times, mix homogeneously, is sub-packed in capsule, obtains final product.
Capsule 2
First by Olibanum 10g, Rhizoma Atractylodis 10g, Radix Pseudostellariae 30g, Herba Ephedrae 20g, Herba Houttuyniae 10g, Herba Eleusines Indicae 20g, Herba Moslae Soochowensis 20g, Herba Taxilli 20g is cut into coarse granule respectively, mix, then the ethanol that determining alcohol is 80% is put into, ethanol did not have above-mentioned raw materials medicine mixture, soak more than 2 hours, the determining alcohol adding 8 times amount accounting for above-mentioned raw materials medicine mixture gross mass be subsequently 80% alcohol heating reflux extract 2 hours, cooling, filter, the determining alcohol again adding 6 times amount accounting for above-mentioned raw materials medicine mixture gross mass in filtering residue be 80% alcohol heating reflux extract 2 hours, filter, the filtrate of twice filtration mixed, obtain the first filtrate, by Caulis Bambusae In Taenia 20g, Herba Pogostemonis 10g, Rhizoma Dryopteris Crassirhizomatis 20g, Herba Peperomiae Dindygulensis 10g, Herba Murdanniae Divergentis 30g, Radix Paeoniae Alba 30g, , Herba Asteris Ageratoidis 30g, Strobilus Cupressi 20g, Folium et Ramulus Callicarpae nudiflorae 20g and Folium Mori 20g is cut into coarse granule respectively, mix, to account for above-mentioned raw materials medicine mixture gross mass 10 times amount 70% ~ 80% alcohol dipping, slowly percolation is complete, obtain percolate, by the first filtrate and percolate mixing, carry out coarse filtration and fine straining with filter press, it is 1.15 that fine straining liquid Three-effect energy-saving concentrator is concentrated into relative density, temperature 60 C, concentrated solution spray drying method, feed liquor speed 6000ml/min, centrifugal speed 6000r/min, inlet temperature 120 DEG C, prepare extract powder, every 100g extract powder adds microcrystalline Cellulose 98g and micropowder silica gel 2g, crosses 80 mesh sieve 3 times, mix homogeneously, is sub-packed in capsule, obtains final product.
Toxicology test
Test example 1: acute toxicity test of the present invention
One, test material:
Animal: Kunming mouse, body weight 21-24g, male and female half and half, Shandong University's biology laboratory breeding.Medicine: granule 1 of the present invention.
Two, method:
1, LD50 calculates: adopt improvement karber's method, mice is divided into 5 groups at random, often organize 10, male and female half and half, dissolved by granule adding distil water, be made into Cmax, by the administration of mice maximum permission capacity, institute is followed successively by 18 to dosage by crude drug amount, 14.4,11.5,9.2,7.4 (g.kg -1), in animal fasting (can't help water) after 18 hours, administration at twice in a day (interval half an hour), each 0.5ml, observes animal dead situation.
2, maximum tolerated dose measures (MTD value): get mice 20, each 10 of male and female.Granule 1 adding distil water is dissolved, is made into maximum concentration, by the maximum tolerated dose of animal, feed device and can twitch to inject to fill with and be as the criterion.In animal fasting (can't help water) after 18 hours, administration at twice in one day (interval half an hour), each 0.5ml (every ml containing crude drug 0.36g), total dose is 18g crude drug/kg.d, 300 times of quite clinical adult 50Kg body weight consumption.Continuous Observation 7 days after administration.
Three, result of the test:
In LD50 calculates when giving mice with maximum acceptable concentration and maximum permission capacity (18g/Kg.d), have no dead mouse, namely LD50 is not measured, ask maximum tolerated dose only, in 7 day observation period, its appetite of animal, activity, hair color, the mental status etc. are all normal, grow normal, there are no death.Namely select the 300 times of doses being equivalent to clinical dosage, and have no adverse reaction, show that acute toxicity is minimum, MTD > 18g/Kg.d.
Experimental example 2: aggregate toxicity is tested:
Capsule of the present invention 1 pair of mice is by 7.69,19.18 and 43.21g crude drug/kg continuous use 15 weeks (1.0ml/100g body weight, every day 2 times) and drug withdrawal after 3 weeks, result shows: the index such as hair, behavior, defecation, body weight, organ weights, hemogram, hepatic and renal function, blood glucose, blood fat of Chinese medicine preparation of the present invention to rat all has no significant effect, internal organs naked eyes do not find that difference change and histological indications show, medication 15 weeks and drug withdrawal are after 3 weeks, and each internal organs of rat are all without obviously changing.After Traditional Chinese medicine preparation capsule agent of the present invention 1 pair of rat long-term prescription is described, toxicity is little, does not also have difference reaction, application safety after drug withdrawal.
Prophylactic tria
Experimental animal
Juvenile Wistar rat 80, cleaning grade, body weight 180 ~ 200 g, is regardless of male and female, is provided by Shandong University's Experimental Animal Center; Influenza A virus A3 strain and dog kidney passage cell strain (MDCK), provided by antiviral drugs research department of study of pharmacy institute of Shandong University.
Medicine and reagent:
Phosphate buffer (PBS), 12 %1640 culture fluid, NaHCO 3solution (7 % tri-distilled water preparation), 0. 1 % trypsin, 10 % chloral hydrate provide by medical college microbial room of Shandong University; Import GIBCO hyclone is provided by Shanghai Yu Sen Bioisystech Co., Ltd; Ribavirin tablet is provided by the large pharmacy of Jinan Fahrenheit; Granule 1 provided by the invention.
Main equipment: TN type table pan torsion bal, superclean bench, ultra cold storage freezer, high speed centrifuge, 37 DEG C of 5 %CO 2incubator, 96 hole few cells plates, GDHP281 type water isolation type electro-heating standing-temperature cultivator.
Experimental technique
The preparation of serum
60 rats are divided into 3 groups (every 20) according to random digits table: granule group provided by the invention, ribavirin western medicine group, blank group.Blank group distilled water gavage.Dilution factor in dosage=clinical usual amounts × animal dose,equivalent coefficient (by body surface area) × culture medium, successive administration 3d, daily 2 times.Before last administration, 12 h are can't help in fasting, 1 h abdominal aortic blood (anaesthetizing with 10 % chloral hydrate 400 mg/ kg before getting blood) after last administration, 2 000 r/ min (radius=10 cm), centrifugal 20 min, separation of serum, then 56 DEG C, 30 min water-bath deactivations, subpackage degerming with the filtering with microporous membrane of 0. 2 μm on super-clean bench, is placed in-20 DEG C of refrigerators for subsequent use.
The mensuration of rat immunity index
Adopt EL ISA test kit, strict by specification operation; Data handling utility specialty statistic software SPSS 12. 0 carries out Data Analysis Services, and Cytokine data adopts one factor analysis of variance, and group difference adopts t inspection.
Contained Serum is to the inhibitory action of CPE caused by influenza virus
Be 10 % with serum-free medium by each Contained Serum diluted sample, 5 %, 2. 5 %, 1. 25 %, tetra-concentration, add MDCK cell monolayer, 37 DEG C hatch 2 h after, suck Contained Serum sample, with 100 × TCID 50virus liquid infects MDCK cell monolayer, puts 37 DEG C, 5 %CO 2continue to cultivate, every day, observation of cell metamorphosis, after cultivating 72 h, with the dyeing of MTT method, surveyed OD value at 490 nm.Be calculated as follows the suppression ratio of sample to CPE caused by influenza virus:
CPE (%)=(experimental port OD value-virus control wells OD value)/normal cell controls hole OD value-virus control wells OD value × 100 %
The experimental result of resisiting influenza virus
The CPE suppression ratio of ribavirin western medicine group is 28%, and adopts granule provided by the invention to be 12% to the suppression ratio of CPE, and comparatively western medicine group more can influenza virus always to adopt medicine provided by the invention.
Improve immunologic function effect
Patient suffers from influenza often because body immune function is deteriorated, and causes poisoning intrusion, and the raising of immunologic function can well the generation of flu-prevention.
In rat blood serum, the impact of IL-2 and IFN-r level, the results are shown in Table 1.
The impact of IL-2 and IFN-r level in table 1 rat blood serum
Group Number of cases/only IL-2 IFN-r
Granule group 20 46.572 +2.939 53.511 +4.098
Western medicine group 20 38.725 +3.660 47.229 +3.090
Blank group 20 32.193 +3.602 36.776 +2.996
As can be seen from Table 1, adopt granule provided by the invention can significantly improve IL-2 and IFN-r level in rat blood serum, improve immune function.
Clinical data
Diagnostic criteria
Clinical diagnosis is with reference to the diagnostic criteria of the People's Republic of China's health industry standard WS28522008 influenza.
Inclusive criteria
1) Chinese medical discrimination meet pyretic toxicity attack lung card, primary symptom: heating, body temperature>=38.5 DEG C; Secondary disease: general pain, pharyngalgia, cough, coughs up phlegm; Simultaneous phenomenon: headache, weak, nasal obstruction; Tongue arteries and veins: red tongue, yellow and greasy fur, or ash is greasy, slippery and rapid pulse; 2) routine blood test: WBC 4.0 ~ 10.0 × 10 9/ L, N % < 75 %; 3) 18 ~ 65 years old age; 4) course of disease is within 48 h.
Exclusion standard
1) above-mentioned inclusive criteria person is not met; 2) there is chronic respiratory tract disease medical history; 3) serious diseases such as cardiovascular, lung, liver, kidney, hemopoietic system are associated with; 4) psychosis patient; 5) to known drug composition allergy sufferers.
Patient data
Case is chosen in January, 2013 in December ,-2013 and is carried out 200 medical routine influenzas of my institute's emergency treatment (pyretic toxicity attacks lung card) patient, be divided into 2 groups at random, treatment group 100 example, man 56 example, female 44 example, 25 ~ 62 years old age, average 45.39 years old, mean body temperature (39.1 ± 0.6) DEG C; Matched group 100 example, man 57 example, female 43 example, 30 ~ 62 years old age, average 43.84 years old, mean body temperature (39.2 ± 0.7) DEG C.2 groups of patients comparing difference not statistically significant (P > 0.05) in sex, age, body temperature etc., has comparability.
Therapeutic Method
General treatment
Two groups of patients all advise have a rest more, drink more water, close observation change of illness state.
Drug therapy
Matched group: oral oseltamivir phosphate, 1 tablet/time, every day 2 times, the course for the treatment of 3 d.Treatment group: the embodiment of the present invention 1 prepare granule 1, every day 2 times, each 5g, the course for the treatment of 3d.
Observational technique
2 groups was all 1 course for the treatment of with 3 d, at viewing duration, and stop using other antiviral, antibiotic medicine.Observe symptom and sign after 2 groups of medication 72h.
Criterion of therapeutical effect
Clinical cure: through controlling in 3 d, heat is castrated cool, body temperature is lower than 37.0 DEG C, and nothing is repeatedly, transference cure; Effective: through controlling 3 d, large heat is moved back, body temperature is close to 37.0 DEG C, and cardinal symptom major part disappears; Effective: through controlling 3 d, large heat is moved back, but body temperature still has repeatedly, cardinal symptom partial disappearance; Invalid: through controlling 3 d, hyperpyrexia, symptom is not improved.
Statistical procedures
Data handling utility specialty statistic software SPSS 12. 0 carries out Data Analysis Services, and Cytokine data adopts one factor analysis of variance, and group difference adopts t inspection.
Two groups of comparitive study, the results are shown in Table 2.
Table 2 liang group treatment 72 as a child efficacy result is compared
Group Cure Effective Effectively Invalid Total effective rate
Treatment group 89 9 2 0 100%
Matched group 73 16 6 5 73%
All above-mentioned this intellectual properties of primary enforcement, not setting restriction this new product of other forms of enforcement and/or new method.Those skilled in the art will utilize this important information, and foregoing is revised, to realize similar implementation status.But all modifications or transformation belong to the right of reservation based on new product of the present invention.
The above is only preferred embodiment of the present invention, and be not restriction the present invention being made to other form, any those skilled in the art may utilize the technology contents of above-mentioned announcement to be changed or be modified as the Equivalent embodiments of equivalent variations.But everyly do not depart from technical solution of the present invention content, any simple modification, equivalent variations and the remodeling done above embodiment according to technical spirit of the present invention, still belong to the protection domain of technical solution of the present invention.

Claims (9)

1. for preventing and treating a medicine for influenza, it is characterized in that: crude drug comprises Olibanum, Caulis Bambusae In Taenia, Rhizoma Atractylodis, Radix Pseudostellariae, Herba Pogostemonis, Rhizoma Dryopteris Crassirhizomatis, Herba Ephedrae, Herba Houttuyniae, Herba Peperomiae Dindygulensis, Herba Murdanniae Divergentis, Herba Eleusines Indicae, Herba Moslae Soochowensis, the Radix Paeoniae Alba, Herba Taxilli, Herba Asteris Ageratoidis, Strobilus Cupressi, Folium et Ramulus Callicarpae nudiflorae and Folium Mori.
2. medicine as claimed in claim 1, is characterized in that: the weight of each crude drug is respectively Olibanum 10g ~ 30g, Caulis Bambusae In Taenia 20g ~ 40g, Rhizoma Atractylodis 10g ~ 30g, Radix Pseudostellariae 30g ~ 50g, Herba Pogostemonis 10g ~ 30g, Rhizoma Dryopteris Crassirhizomatis 10g ~ 30g, Herba Ephedrae 20g ~ 40g, Herba Houttuyniae 10g ~ 30g, Herba Peperomiae Dindygulensis 10g ~ 30g, Herba Murdanniae Divergentis 20g ~ 40g, Herba Eleusines Indicae 10g ~ 30g, Herba Moslae Soochowensis 10g ~ 30g, Radix Paeoniae Alba 20g ~ 40g, Herba Taxilli 10g ~ 30g, Herba Asteris Ageratoidis 20g ~ 40g, Strobilus Cupressi 10g ~ 30g, Folium et Ramulus Callicarpae nudiflorae 10g ~ 30g and Folium Mori 10g ~ 30g.
3. medicine as claimed in claim 1 or 2, is characterized in that: the weight of each crude drug also can be respectively Olibanum 10g ~ 20g, Caulis Bambusae In Taenia 20g ~ 30g, Rhizoma Atractylodis 10g ~ 20g, Radix Pseudostellariae 30g ~ 40g, Herba Pogostemonis 10g ~ 20g, Rhizoma Dryopteris Crassirhizomatis 10g ~ 20g, Herba Ephedrae 20g ~ 30g, Herba Houttuyniae 10g ~ 20g, Herba Peperomiae Dindygulensis 10g ~ 20g, Herba Murdanniae Divergentis 20g ~ 40g, Herba Eleusines Indicae 10g ~ 30g, Herba Moslae Soochowensis 10g ~ 30g, Radix Paeoniae Alba 20g ~ 40g, Herba Taxilli 10g ~ 30g, Herba Asteris Ageratoidis 20g ~ 40g, Strobilus Cupressi 10g ~ 30g, Folium et Ramulus Callicarpae nudiflorae 10g ~ 30g and Folium Mori 10g ~ 30g.
4. the medicine as described in claims 1 to 3, is characterized in that: the weight of each crude drug also can be respectively Olibanum 10g ~ 30g, Caulis Bambusae In Taenia 20g ~ 40g, Rhizoma Atractylodis 10g ~ 30g, Radix Pseudostellariae 30g ~ 50g, Herba Pogostemonis 10g ~ 30g, Rhizoma Dryopteris Crassirhizomatis 10g ~ 30g, Herba Ephedrae 20g ~ 40g, Herba Houttuyniae 10g ~ 30g, Herba Peperomiae Dindygulensis 10g ~ 30g, Herba Murdanniae Divergentis 30g ~ 40g, Herba Eleusines Indicae 20g ~ 30g, Herba Moslae Soochowensis 20g ~ 30g, Radix Paeoniae Alba 30g ~ 40g, Herba Taxilli 20g ~ 30g, Herba Asteris Ageratoidis 30g ~ 40g, Strobilus Cupressi 20g ~ 30g, Folium et Ramulus Callicarpae nudiflorae 20g ~ 30g and Folium Mori 20g ~ 30g.
5. the medicine as described in Claims 1-4, is characterized in that: the weight of each crude drug also can be respectively Olibanum 20g, Caulis Bambusae In Taenia 30g, Rhizoma Atractylodis 20g, Radix Pseudostellariae 40g, Herba Pogostemonis 20g, Rhizoma Dryopteris Crassirhizomatis 20g, Herba Ephedrae 30g, Herba Houttuyniae 20g, Herba Peperomiae Dindygulensis 20g, Herba Murdanniae Divergentis 30g, Herba Eleusines Indicae 20g, Herba Moslae Soochowensis 20g, Radix Paeoniae Alba 30g, Herba Taxilli 20g, Herba Asteris Ageratoidis 30g, Strobilus Cupressi 20g, Folium et Ramulus Callicarpae nudiflorae 20g and Folium Mori 20g.
6. the medicine as described in claim 1 to 5, is characterized in that: described medicine can be prepared into tablet, granule, capsule, oral liquid, syrup.
7. the preparation method of medicine described in claim 1 to 6, is characterized in that, comprising:
The first step, first by Olibanum, Rhizoma Atractylodis, Radix Pseudostellariae, Herba Ephedrae, Herba Houttuyniae, Herba Eleusines Indicae, Herba Moslae Soochowensis, Herba Taxilli is cut into coarse granule respectively, mix, then the ethanol that determining alcohol is 70% ~ 80% is put into, ethanol did not have above-mentioned raw materials medicine mixture, soak more than 2 hours, the determining alcohol adding 8 times amount accounting for above-mentioned raw materials medicine mixture gross mass be subsequently 70% ~ 80% alcohol heating reflux extract 2 hours, cooling, filter, the determining alcohol again adding 6 times amount accounting for above-mentioned raw materials medicine mixture gross mass in filtering residue be 70% ~ 80% alcohol heating reflux extract 2 hours, filter, the filtrate of twice filtration is mixed, obtain the first filtrate,
Second step, Caulis Bambusae In Taenia, Herba Pogostemonis, Rhizoma Dryopteris Crassirhizomatis, Herba Peperomiae Dindygulensis, Herba Murdanniae Divergentis, the Radix Paeoniae Alba, Herba Asteris Ageratoidis, Strobilus Cupressi, Folium et Ramulus Callicarpae nudiflorae and Folium Mori are cut into coarse granule respectively, mix, to account for above-mentioned raw materials medicine mixture gross mass 8 ~ 12 times amount 70% ~ 80% alcohol dipping, slowly percolation is complete, obtains percolate;
3rd step, by the first filtrate and percolate mixing, carry out coarse filtration and fine straining with filter press, it is 1.15 that fine straining liquid Three-effect energy-saving concentrator is concentrated into relative density, temperature 60 C; Concentrated solution spray drying method, feed liquor speed 6000ml/min, centrifugal speed 6000r/min, inlet temperature 120 DEG C, prepares extract powder;
4th step, adds adjuvant according to the dosage form of various needs, prepares corresponding dosage form product in extract powder prepared by the 3rd step.
8. the preparation method of medicine as claimed in claim 7, it is characterized in that: when dosage form prepared by described medicine is granule, described 4th step is specially further and adds dextrin and sucrose in extract powder, the extract powder of every 100g, the addition of dextrin is 100g ~ 120g, the addition of sucrose is 120g ~ 150g, be placed in wet granulator, mix 3 ~ 8 minutes, make granule, send in vacuum drier and carry out vacuum drying, temperature of charge is 40 ~ 70 DEG C, vacuum is-0.08Mpa ~-0.12Mpa, charging rate is 15 ~ 20L/h, material strip transfer rate is 20 ~ 30cm/min, subpackage after dry, 5g mono-bag.
9. the preparation method of medicine as claimed in claim 7, it is characterized in that: when dosage form prepared by described medicine is capsule, described 4th step is specially further and adds microcrystalline Cellulose 98g and micropowder silica gel 2g in extract powder described in every 100g, cross 80 mesh sieve 3 times, mix homogeneously, be sub-packed in capsule, obtain final product.
CN201410807420.0A 2014-12-23 2014-12-23 Medicine for preventing and treating flu Pending CN104524284A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106377715A (en) * 2016-11-04 2017-02-08 覃忠强 Traditional Chinese medicine composite capable of preventing and curing flu, and preparation method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1446559A (en) * 2002-03-27 2003-10-08 曾宽生 Medicine for treating common cold and its preparation method
CN1526415A (en) * 2003-03-04 2004-09-08 云南省药物研究所 Medicine composition for treating cold
CN101564459A (en) * 2008-04-24 2009-10-28 北京以岭药业有限公司 Application of Chinese medicinal composition in preparing medicament for treating upper respiratory tract infection

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1446559A (en) * 2002-03-27 2003-10-08 曾宽生 Medicine for treating common cold and its preparation method
CN1526415A (en) * 2003-03-04 2004-09-08 云南省药物研究所 Medicine composition for treating cold
CN101564459A (en) * 2008-04-24 2009-10-28 北京以岭药业有限公司 Application of Chinese medicinal composition in preparing medicament for treating upper respiratory tract infection

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
刘道清: "《中药别名大辞典》", 31 January 2013, 中原农民出版社 *
孟靓靓: "《传染病防治手册》", 28 February 2014, 金盾出版社 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106377715A (en) * 2016-11-04 2017-02-08 覃忠强 Traditional Chinese medicine composite capable of preventing and curing flu, and preparation method thereof

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