CN101108200A - Composition of starwort sulphonic acid or vitriolic acid polyoses ester total phenolic glycoside and method of preparing the same and antiviral application - Google Patents

Abstract

The invention relates to a kind of natural medicine of broad spectrum antibiotic. At present, the broad spectrum antibiotic medicine with high effect and safety is at shortage all round the world. The invention is intended to extract laminarinsulphate or sulphonic acid sugar ester or sulphosalts from plant chickweed or other chickweed plant with two resin adsorption methods or a water extraction and alcohol precipition method. The spectrum antibiotic in the invention is distributed under 50,000 in the formula weight formed by carbon glycosidic bond and/or oxide glycosidic bond with phenol, especially the total flavones comprising apigenin. However, the invention mainly acts as total phenolic glycoside with the formula weight under 4,000. Besides, the invention can form brownish compound with the total flavones comprising apigenin and the glycosidic ingredients without sulfur element, so as to be applied as broad spectrum antibiotic drug. Therefore, the compound in the invention can be applied to cure ADIS virus, hepatitis virus, influenza virus and parainfluenza virus comprising SARS, adenovirus, verruca acuminate virus, enterovirus, mumps virus, herpes simplex virus, herpes zoster virus and varicella. No toxic effect has been found in the application. What is more, the invention can be made into 10 sorts of formulation, disinfector and health-improving products.

Description

Herba stellariae mediae sulfonic acid or sulfated polysaccharide ester total phenols glycoside composition and preparation method thereof are used with antiviral

One, technical field:

The present invention relates to the sulfated polysaccharide ester or sulfonic acid polysaccharide ester and its esters that from plant Herba stellariae mediae or other a kind of Stellaria plant, extract, with phenols especially with the total flavones that comprises apigenin with the carbon glycosidic bond or/and the molecular weight distribution that the oxygen glycosidic bond forms 50, below 000, but be mainly molecular weight distribution 4, the total phenolic glycoside composition of a class below 000 is with the total flavones that comprises apigenin and do not contain the pale brown colour cell compound that the glucosides class composition of element sulphur forms and use as broad-spectrum antiviral medicament.

Wherein the total phenols glycoside composition of the total phenols glycoside composition of Herba stellariae mediae sulfated polysaccharide ester or Herba stellariae mediae sulfonic acid polysaccharide ester and the total flavones that comprises apigenin and the ratio that do not contain the glucosides class composition of element sulphur thereof are 9.0～9.8 to 1.0～0.2.

Two, background technology:

By retrieval U.S.'s " chemical abstracts " (Chemical Abstracts) till the 134th volume, the chemical constituent of the Stellaria plant of being reported mainly is flavone and the former class of flavonoid glycosides, Saponin and Saponin, ring peptide class, ferulic acid and esters, chlorogenic acid, neochlorogenic acid, caffeic acid, quininic acid, ascorbic acid class, oxalic acid and calcium oxalate, monoacyl galactose lipoid, alkaloids, galactopyranose-SN-glycero class, chondrillasterol, stigmastenol, sitosterol class or the like from nineteen twenty to calendar year 2001.

The inventor was to disclose the application as antiviral drugs of the total organic phenolic acid that contains more element sulphur and calcium constituent from Stellaria plant Herba stellariae mediae or other a kind of Stellaria plant in the molecular structure that extracts and glucoside compound and high polarity compound compositions such as total flavones and glucosides class thereof thereof in CN 1377680A and two parts of patents of CN 1498630A at publication number once.

Other the patent disclosure of publication number CN1521193A is arranged and claim with hot rare alcohol from the Stellaria plant, extract molecular weight distribution 4000～2000000 and the canescence polysaccharide composition that contains peptide have antivirus action.

But do not see as yet that so far extraction separation is to sulfated polysaccharide ester or sulfonic acid polysaccharide ester and its esters from the Stellaria plant, with phenols especially with the total flavones that comprises apigenin with the carbon glycosidic bond or/and the molecular weight distribution that the oxygen glycosidic bond forms 50, below 000, but be mainly molecular weight distribution 4, the total phenolic glycoside composition of a class below 000 is as the report of broad-spectrum antiviral medicament application.

Three, summary of the invention:

1, the technical problem to be solved in the present invention: provide a kind of from Herba stellariae mediae or the isolating sulfated polysaccharide ester of other a kind of Stellaria plant extract or sulfonic acid polysaccharide ester and its esters, with phenols especially with the total flavones that comprises apigenin with the carbon glycosidic bond or/and the molecular weight distribution that the oxygen glycosidic bond forms 50, below 000, but be mainly molecular weight distribution 4, the total flavones that comprises apigenin of the total phenolic glycoside composition of class Herba stellariae mediae sulfated polysaccharide ester below 000 or total phenolic glycoside composition of Herba stellariae mediae sulfonic acid polysaccharide ester and 2%～10% and do not contain the pale brown colour cell compound that the glucosides class composition of element sulphur is formed, use as broad-spectrum antiviral medicament, and have better broad-spectrum disease resistance toxic action, also provide a kind of yield higher preparation method.

2, the technical solution used in the present invention: on the disclosed CN 1377680A of the inventor and two parts of patent bases of CN1498630A, after further investigation, according to relevant spectral data and drug effect, result of the tests such as toxicity, a kind of extraction separation obtains from plant Herba stellariae mediae Stellaria media (L.) Cyr. and other a kind of Stellaria plant sulfated polysaccharide ester or sulfonic acid polysaccharide ester and its esters and phenols further are provided, especially with the total flavones that comprises apigenin with the carbon glycosidic bond or/and the molecular weight distribution that the oxygen glycosidic bond forms 50, below 000, but be mainly molecular weight distribution 4, Herba stellariae mediae sulfated polysaccharide ester total phenols glycoside composition below 000, or the total flavones that comprises apigenin of the total phenols glycoside composition of Herba stellariae mediae sulfonic acid polysaccharide ester and 2%～10% and do not contain the pale brown colour cell compound (to call " compositions " in the following text) that the glucosides class composition of element sulphur is formed, use as broad-spectrum antiviral medicament, and have better antivirus action.

Also provide simultaneously to improve on the resin column and improve the compositions yield behind the elution requirement and with the preparation method of aqueous extraction-alcohol precipitation technology.

Compositions of the present invention, be from a following kind of plant, to extract, these plants have comprised Stellaria plant Stellaria L. and cattle Stellaria plant Malachium Fries following 79 kinds, i.e. Herba stellariae mediae Stellariamedia (L.) Cyr., Stellaria alsine Grim. Stellaria alsine Grimm., brown lobe Stellaria alsine Grim. Stellaria alsinevar.phaeuspetala Hand.-Mazz., Anhui Herba stellariae mediae Stellaria anhwiensis Migo., blunt calyx Herba stellariae mediae Stellaria amblyosepala Schrenk., apicule Herba stellariae mediae Stellaria apiculata Wils., Herba malachii aquatici Stellariaaquatica (L) Scop., the husky Herba stellariae mediae Stellaria arenaria Maxim that gives birth to, Alishan Herba stellariae mediae Stellariaarisanensis Hayata., slender lobule Alishan Herba stellariae mediae Stellaria arisanensis var.leptophylla Hayata., north Herba stellariae mediae Stellaria borealis Bigel., short lobe Herba stellariae mediae Stellaria brachypetala Bge., long lobe Herba stellariae mediae Stellaria bungeana Fenzl., northeast Herba stellariae mediae Stellaria cherleriae (Fisch.) Will., China Herba stellariae mediae Stellaria chinensis Regel, Taiwan Herba stellariae mediae Stellaria cicrantha Hayata, thick leaf Herba stellariae mediae Stellariacrassifolia Ehrh., wrinkle leaf Herba stellariae mediae Stellaria crispate Wall., David's Herba stellariae mediae Stellaria davidiiHemsl., the Herba stellariae mediae Stellaria decumbens Edgew. that crouches lays down, the needle-like Herba stellariae mediae Stellaria decunbensvar.acicularia Edgew.et Hook.f. that crouches that lays down, southwest Herba stellariae mediae Stellaria delavayi Franch., Stellaria dianthifolia Williams Stellaria dianthifolia Williams, forked cyme Herba stellariae mediae Stellaria dichasioides Williams, bifid Herba stellariae mediae Stellaria dichotoma L., narrow leaf bifid Herba stellariae mediae Stellaria dichotoma var.lanceolataBge., line leaf bifid Herba stellariae mediae Stellaria dichotoma var.stepheniana Willd., Herba stellariae mediae Stellariadiffusa Wills. looses in the shop, turn over white Herba stellariae mediae Stellaria discolor Turcz., Stellaria diversiflora Maxim. Stellaria diversifloraMaxim., the different colored Herba stellariae mediae Stellaria diversiflora var.gymnandra Franch. of naked stamen, concave veins Herba stellariae mediae Stellaria depressa Schnid., Du Shi Herba stellariae mediae Stellaria duthiei Gandoger, line stem Herba stellariae mediae Stellariafilicaulis Mak., line handle Herba stellariae mediae Stellaria filipes Komar., spend more Herba stellariae mediae Stellaria florida Fisch., standing grain leaf Herba stellariae mediae Stellaria graminea L., dredge pubescence standing grain leaf Herba stellariae mediae Stellaria graminea var.pilosulaMaxim., turn green standing grain leaf Herba stellariae mediae Stellaria graminea var.viridescens Maxim., Jiangzi's Herba stellariae mediae Stellaria gyantsensis Williams, XIACAO Herba stellariae mediae Stellaria gypsophiloides Fenzl., Stellaria henryi williams Stellaria henryi Williams, the Herba stellariae mediae Stellaria hsinganensis Kitagawa of Xingan, introversion Herba stellariae mediae Stellaria infracta Maxim., slender lobule Herba stellariae mediae Stellaria leptophylla Hance, Stellaria maximowixziana Franch. Stellariamaximowixziana Franch., Herba stellariae mediae Stellaria media (L.) Cyr., Stellaria micrantha Hayata Stellariamicrantha Hayata, gentle Herba stellariae mediae Stellaria mitans Williams, goose intestinal Herba stellariae mediae Stellaria neglectaWeihe, Herba stellariae mediae Stellaria neo-palustris Kitagawa is given birth in new natural pond, eight stamen Herba stellariae mediae Stellaria octandraFobedim., raspberry Herba stellariae mediae Stellaria oxycoccoides Komar., Herba stellariae mediae Stellaria palustris L. is given birth in the natural pond, exhibition leaf Herba stellariae mediae Stellaria patentifolia Kitagawa, handle flower Herba stellariae mediae Stellaria peduncularis Bge., handle leaf Herba stellariae mediae Stellaria petiolaris Hand-Mazz., Herba stellariae mediae Stellaria pilosa Franch. becomes mildewed, imitation stone is given birth to Herba stellariae mediae Stellaria pseudosaxatilis Hand.-Mass., blinks Stellaria pusilla Schmid., flint lobe Herba stellariae mediae Stellaria radians L., net arteries and veins Herba stellariae mediae Stellaria reticulivena Hayata, rock Herba stellariae mediae Stellariarupestris Hemsl., stone is given birth to Herba stellariae mediae Stellaria saxatilis Buch.-Ham., embrace stem stone and give birth to Herba stellariae mediae Stellariasaxatilis var.amplexicaulis Hand.-Mazz., accurate Ge Er Herba stellariae mediae Stellaria soongorica Roshev., Su Shi Herba stellariae mediae Stellaria souliei Williams, star hair Herba stellariae mediae Stellaria stellato-pilosa Hayata, garden calyx Herba stellariae mediae Stellaria strongylosepala Hand.-Mazz., intend umbrella flower Herba stellariae mediae Stellaria subumbellataEdgew., little fine hair Herba stellariae mediae Stellaria tomentella Ohwi, three type Herba stellariae mediae Stellaria trimorpha Nakai, Turkestan Herba stellariae mediae Stellaria turkestanica Schischk., wetland Herba stellariae mediae Stellaria uda Williams, umbrella flower Herba stellariae mediae Stellaria umbellata Turcz., LVHUA Herba stellariae mediae Stellaria virdiflora Pax et O.Hoffm., Stellaria wushanensis Williams Stellaria wushanensis Williams, five Herba stellariae mediae Stellaria wutaicaHand.-Mazz., Yunnan Herba stellariae mediae Stellaria yunnanensis franch.j or cattle Stellaria plant cattle Herba stellariae mediae Malachium aquaticum (L.) Fries etc.

Further investigation find this from Herba stellariae mediae and other a kind of Stellaria plant extraction separation to compositions use as broad-spectrum antiviral medicament and have following characteristics:

1), I once disclosed in CN 1377680A and two parts of patents of CN 1498630A and had contained more element sulphur and calcium constituent in the said composition, now find it is to have formed Herba stellariae mediae sulfated polysaccharide esters or sulfonic acid polysaccharide esters structure and calcium salt thereof, and can be formed other metallic salt by replacement calcium such as other metal such as potassium, sodium, copper, ferrum by it through further investigation.

2), since the phenolic glycoside class of above-mentioned sulfated polysaccharide ester or sulfonic acid polysaccharide ester on its NMR (Nuclear Magnetic Resonance) spectrum except that the phenolic hydroxyl group signal is arranged, also occur saturated or/and undersaturated sugared hydroxyl signal shows that this is to have formed saturated or/and the total phenolic glycoside composition of a class of undersaturated sulfated polysaccharide ester or sulfonic acid polysaccharide ester.

3), Herba stellariae mediae sulfated polysaccharide ester or sulfonic acid polysaccharide ester and its esters especially with the total flavonoid that comprises apigenin with the carbon glycosidic bond or/and the oxygen glycosidic bond has formed the total phenolic glycoside composition of a class.

4), compositions records its molecular weight distribution through polydextran gel should be below 50,000, but are mainly the total phenols glycoside composition of molecular weight distribution at Herba stellariae mediae sulfated polysaccharide ester total phenols glycoside composition below 4,000 or Herba stellariae mediae sulfonic acid polysaccharide ester

5), compositions can obtain 2%～10% the total flavones that comprises apigenin and not contain the glucosides class composition of element sulphur after Sephadex LH20 separates, so in the compositions total phenols glycoside composition of the total phenols glycoside composition of Herba stellariae mediae sulfated polysaccharide ester or Herba stellariae mediae sulfonic acid polysaccharide ester with total flavones and the ratio that does not contain the glucosides class composition of element sulphur be 9.0～9.8 to 1.0～0.2.

6), the intensity of compositions antivirus action, with sulfated polysaccharide ester in its compound structure or sulfonic acid polysaccharide ester partly proportion be directly proportional, with phenols partly proportion be inverse ratio; Therefore, along with molecular weight progressively increases, when the glucosides of sulfated polysaccharide ester in its structure or sulfonic acid polysaccharide ester partly proportion by 50%～55% increase to 80%～90%, phenol partly proportion by 50%～45% be reduced to only account for about 20%～10% the time, its solution colour also progressively becomes brownish red to dark brown red by foresythia, its antivirus action also progressively strengthens, and total flavones and not contain the antivirus action of glucosides class composition of element sulphur the most weak in the compositions.

7), compositions is when the polyamide thin layer chromatography, the chromatography speckle very clearly manifests dark brown red, sepia, brown, pale brown color, and fluorescence speckle such as yellow under the 365nm ultraviolet light, the fluorescence speckle that under the 254nm ultraviolet light, also can manifest same color, just a little less than.

8), having partly in the compositions, chemical compound has polymerism, polymerizable also obtains a kind of component that is the fluorescence speckle of " brownish black " under the 365nm ultraviolet light, this component often rests on initial point or Rf value below 0.15 during thin layer chromatography, this is a special color fluorescence speckle not seen before, shows that this compounds has bigger molecular weight and its antivirus action is also the strongest; But reach 50,000 even present the block or Powdered thing of a kind of nearly black when bigger when it is aggregated to molecular weight, its dissolubility also reduces.

9), brown, brownish red of compositions formation soluble in water or dark brown brown clear solution.

10), from compositions, separate the monomeric compound aqueous solution that obtains and two ultraviolet absorption peaks are arranged at 260nm～273nm and 327～335nm, show that it is the flavone compound with benzoyl and cinnamyl structure, further research wherein comprises apigenin as can be known at least, and with carbon glycosidic bond or oxygen glycosidic bond and saccharide formation total flavonoid glycoside compounds.

11), the monomeric compound that obtains both can manifest the not good merchantable of phenols with the reaction of ferric chloride test solution or tea is brown deeply because of separating in the compositions, and new absworption peak appears about 405nm～430nm, can present the pale brown color of sugar and new absworption peak about 480nm, occur with phenol-strong sulfuric acid response again simultaneously, so compositions is made up of a kind of total phenols glycosides compound.

3, compositions has following beneficial effect:

But the compositions antiviral comprises: Respirovirus and papovavirus, enterovirus, mumps virus, herpes simplex virus, varicella zoster virus and varicella zoster viruss etc. such as HIV (human immunodeficiency virus), hepatitis virus, the influenza virus that comprises high pathogenic avian influenza virus, parainfluenza virus, adenovirus.

Four, the specific embodiment:

One), the preparation of compositions method comprises following three kinds:

1, its first kind of preparation method: the bright grass of plant Herba stellariae mediae or other a kind of Stellaria plant or fresh and dried grass are cleaned silt, are pulverized the back and extract aqueous solution, with this aqueous solution through precipitation, centrifugal or filter after obtain liquid A; With liquid A by the macroporous resin column handled well in advance to adsorb the composition of described compositions, wash post with water, with macroporous resin column heat the back with thermal distillation washing post to clean impurity, collect effusive dark brown distilled water liquid, reuse is heated back concentration at the eluting from the resin column of the lower alcohol below 59%, and collect brownish red or the dark brown-red solution that eluting obtains, to merge with the dark brown water liquid of collecting behind this brownish red or the dark brown-red solution recovery ethanol, be concentrated into than weigh about 0.8 leave standstill after centrifugal again removal precipitate, continue to be concentrated into proportion 1.00 to 1.20 and afterwards pass through spray drying or vacuum drying promptly, compositions character and character are: the pale brown toner powder that a kind of tool Chinese medicine dry extract is common, common Chinese medicine dry extract abnormal smells from the patient is arranged, its stable in properties, soluble in water, bitterness slightly;

Wherein column temperature is 40 ℃～59 ℃, and lower alcohol comprises methanol, ethanol, propanol, n-butyl alcohol, the isobutanol below 59%; Preferred 50 ℃～55 ℃ column temperature and 50%～55% ethanol of uniform temp.

2, its second kind of preparation method: the back is cleaned, pulverized to the bright grass of plant Herba stellariae mediae or other a kind of Stellaria plant or bright Radix Glycyrrhizae extract aqueous solution, with this aqueous solution through precipitation, centrifugal or filter after obtain liquid A; With this liquid A through the anionite post, described compositions composition is adsorbed on the post, with sodium chloride solution the post of described compositions composition after heat eluted, again through desalting processing, leave standstill after being concentrated into proportion about 0.8, centrifugal removal precipitate, continue again to be concentrated into than weighing the spray-dried or vacuum drying in 1.00 to 1.20 backs promptly, compositions character and character are: a kind of have the common pale brown toner of a Chinese medicine dry extract end, common Chinese medicine dry extract abnormal smells from the patient is arranged, its stable in properties, soluble in water, slightly bitterness;

Wherein the anionite post comprises weak anion exchange resin post and cellulose anion exchanger post; Column temperature is 40 ℃～59 ℃, preferred 50 ℃～55 ℃.

3, its the third preparation method: bright grass or the bright Radix Glycyrrhizae of plant Herba stellariae mediae or other a kind of Stellaria plant are cleaned, pulverize the back and extract aqueous solution, with this aqueous solution through the precipitation, centrifugal or filter after be evaporated to proportion about about 0.8, add lower alcohol and make concentration of lower alcohols reach 75%, a large amount of muddinesses promptly appear in solution, leave standstill about 12 hours, the sucking-off supernatant, precipitate through centrifugal or filter the compositions crude product, this crude product reuse pure water dissolving back is added lower alcohol to be made and reaches 85% concentration and carry out the secondary precipitate with ethanol, leave standstill the sucking-off supernatant about 12 hours, precipitate is added an amount of dehydrated alcohol and washing with acetone through decompress filter and timely priority, sucking filtration is extremely done, and promptly gets powdered composition through the proper temperature vacuum drying immediately.

4, compositions is used as antiviral drugs and can be made following dosage form at least:

1). injection can be used for treating the various viral diseases such as viral pneumonia that acquired immune deficiency syndrome (AIDS), hepatitis, the viral atypical pneumonia that causes of SAS, highly pathogenic bird flu virus H 5 N 1 type etc. cause.

2). injectable powder can be used for treating the atypical pneumonia of acquired immune deficiency syndrome (AIDS), hepatitis, the initiation of SAS virus, the various viral diseases such as viral pneumonia that the highly pathogenic bird flu virus H 5 N 1 type causes.

3). aerosol is used for children's and treats influenza, parotitis etc., and can be used as the antiviral disinfectant of air and oral cavity, health product or antiviral functional food.

4). buccal tablet or chewable tablet, be used for the treatment of parotitis etc., can be used as the antiviral disinfectant in air and oral cavity, health product or antiviral functional food.

5). capsule, the oral various viral diseases such as acquired immune deficiency syndrome (AIDS), hepatitis, influenza that are used for the treatment of.

6). microcapsule, in order to slow releasing pharmaceutical treatment chronic viral diseases.

7). nasal drop, be used for the treatment of influenza etc., also can be used as the antiviral disinfectant of nasal cavity, health product etc.

Nasal drop also can be by the nebulizer inhalation that atomizes, in order to treatment treatment viral pneumonia, and the atypical pneumonia that causes as SAS virus, the viral pneumonia that the highly pathogenic bird flu virus H 5 N 1 type causes etc.

8). membrane or liniment etc. are used for treating for skin disease such as herpes, condyloma acuminatum.

9). mucilage is used for the treatment of dermatosiss such as herpes.

10). water preparation is used for the clinical dermatosiss such as treatment herpes, condyloma acuminatum of directly smearing.

11). the liquid chewing gum can be used as oral cavity antiviral disinfectant, antiviral health product or functional food.

12). chewing gum can be used as oral cavity antiviral disinfectant, antiviral health product or functional food etc.

Two), the embodiment of compositions:

1, with the embodiment 1 of first method: after getting the bright careless 30kg of the Herba stellariae mediae of choosing clean impurity and cleaning earth, pulverize with tap water, centrifugal, filter, extract medicinal liquid, residue discards and can be made into greenfeed or resigns from office and return home and make fertilizer; With medicinal liquid through precipitation, centrifugal or filter after promptly obtain liquid A, constantly by the commercially available macroporous resin column of id30cm * 120cm, the control flow velocity is at 3ml/min to 6ml/min with this liquid A.As seen macroporous resin column from top to bottom becomes a kind of brownish red or dark brown brown is filled medicine until pillar gradually.Discard effusive liquid in the pillar, and earlier with the residual liquid in the clean post of tap water.With 55 ℃ of distilled water wash macroporous resin column of about 2 times of column volumes, discard effusive at first colourless and water liquid that color and luster is more light, collect effusive subsequently dark brown water liquid.This moment, macroporous resin column was heated to 45 ℃～50 ℃, and continuing is about 50% ethanol elution of 3 times of amounts of column volume and collects the brownish red alcoholic solution with 55 ℃, and this routine consumption is about the ethanol of 300L 50%.Alcoholic solution is reclaimed ethanol through vacuum drying apparatus, the gained concentrated solution is concentrated into proportion 0.85 with the dark brown water liquid merging of collecting, be about about 1010ml, standing over night, centrifugal 5 minutes then with 4000r/min, discard precipitate, supernatant through 0.5 μ m membrane filtration in sterilized clean container, becoming proportion through concentrating under reduced pressure again under aseptic condition is 1.1 thick paste shape, and spray-dried or vacuum drying promptly gets compositions; Compositions is pale brown color loose powder, and the common abnormal smells from the patient of Chinese medicine is arranged, count 80.38g, yield is calculated as 2.68 ‰ by bright grass, makes compositions 606g altogether with this method repeatedly.

2, with the embodiment 2 of second method: get the dried herb 5kg of fresh Herba stellariae mediae, clean earth with tap water after, pulverize, centrifugal, extract medicinal liquid; Residue discards, and can provide and make greenfeed or resign from office and return home and make fertilizer.With medicinal liquid through precipitation, centrifugal or filter after promptly obtain liquid A, with the commercially available anion-exchange resin column of this liquid A by id 10cm * 120cm, after adsorbing described compositions composition, clean the weak-base anion-exchange resin post with water recently distilled that is about 3 times of column volumes or deionized water, discard from post effusively by light yellow thin out gradually until the almost colourless post liquid of washing, this routine consumption is about 30 L water; Then resin column is heated to 45 ℃～50 ℃ continue with 2 times to column volume and to be heated to about 55 ℃ concentration be that the NaCl solution of 2N will be adsorbed on the rapid eluting of described compositions composition on the post and collect this dark brown red eluent, this routine consumption is 20 L saline solution.This saline solns suitably is concentrated into is placed on about 750ml in the semipermeable membrane bag, successively tap water and distilled water are dialysed until solution to AgNO ₃Solution reaction is very weak or do not have till the saline taste; The back gained dark brown red solution of will dialysing is transferred to that drying under reduced pressure to proportion 0.82 is thick in the vacuum drying apparatus, is about 400ml, and standing over night discarded precipitate in centrifugal 5 minutes with 4000r/min then; Supernatant again through 0.5 μ m membrane filtration in sterilized clean container, under aseptic condition, reach proportion 1.05 through concentrating under reduced pressure, get pale brown toner end through vacuum drying or spray drying again, general Chinese medicine abnormal smells from the patient is arranged, altogether 71.65g, yield is calculated by Radix Glycyrrhizae and is about 1.433%, makes highly finished product 512.73g altogether with this method.

3, with the embodiment 3 of the third method: after getting the bright Radix Glycyrrhizae 5kg of plant Herba stellariae mediae and cleaning, pulverize, water 15kg, 15kg extract twice, merge obtained aqueous solution, with this aqueous solution through precipitation, centrifugal or filter after obtain liquid; Is about 0.8 with this liquid through being evaporated to proportion, add 95% ethanol, make concentration of ethanol reach 75%, a large amount of muddinesses promptly appear in solution, leave standstill and spent the night in 12 hours, the sucking-off supernatant discards, with the lower sediment thing through centrifugal or filter the compositions crude product, this crude product reuse 400ml pure water dissolving back is added lower alcohol to be made and reaches 85% concentration and carry out the secondary precipitate with ethanol, leave standstill the sucking-off supernatant about 12 hours, precipitate is in time successively added an amount of dehydrated alcohol 350ml and acetone 350ml washing through the decompress filter dry doubling, sucking filtration is to doing, and promptly get powdered composition 74.29g through 55 ℃ of vacuum dryings, make 465g altogether with this method.

After repeatedly getting 10g composition powder usefulness 30ml water dissolution, separate, all can obtain opalescent dark-brown solution at first through the Sephadex of id4.5 * 55cm LH20 post water chromatography eluting, be the some of molecular weight distribution maximum, about 4,000～50,000, account for 0.5%～2% of compositions; Thereafter obtain the dark-brown clear solution, obtain the block or Powdered dry extract of nearly brownish black behind concentrating under reduced pressure and the vacuum drying, its molecular weight distribution is about 2,000～4,000, account for 10%～20% of compositions, more than two partly be the strongest part of antivirus action; Thereafter obtain brown-red solution, concentrating under reduced pressure also obtains dark brown yellow bulk or Powdered dry extract behind vacuum drying, and its molecular weight distribution is about 900～2, and 000 and have strong antivirus action, account for 65%～75% of compositions; More than three all be partly by sulfated polysaccharide ester or sulfonic acid polysaccharide ester and its esters, with phenols especially with flavonoid for example apigenin etc., with the carbon glycosidic bond or/and the class total phenols glycoside that the oxygen glycosidic bond forms.Obtain fresh yellow solution at last, obtain yellow dry extract behind concentrating under reduced pressure and vacuum drying, it is the molecular weight distribution minimum, about below 900, be the glucosides class composition that comprises the total flavones of apigenin and do not contain element sulphur, its antivirus action is the most weak, accounts for 2%～10% of compositions.

When table 1. provided on macroporous resin column the eluting compositions, variations in temperature was to the influence of yield:

Among table 1. embodiment 1 from post during the eluting compositions variations in temperature to the influence of yield

Numbering	Temperature	The medicine color and luster	Yield (bright grass meter)	Remarks
					1 2 3 4 5	30 ℃ 40 ℃ 50 ℃ 59 ℃ of about 15 ℃ room temperatures	The obfuscation of reddish brown light yellow complexion dark brown red dark brown red dark brown red obfuscation dark brown red	2.19‰ 2.47‰ 2.53‰ 2.68‰ 2.54‰	Usually adopt

Concentration of alcohol changed the influence to yield when table 2. was given on macroporous resin column eluting compositions:

Among table 2. embodiment 1 from post during the eluting compositions concentration of alcohol change influence to yield

Numbering	Concentration of alcohol %	The medicine color and luster	Yield (bright grass meter)	Remarks
					1 2 3 4 5 6	20％ 30％ 40％ 50％ 60％ 70％	The reddish brown light yellow complexion dark brown red dark brown red dark brown red dark dark brown red dark brown red blackout that shades	2.25‰ 2.31‰ 2.34‰ 2.68‰ 2.45‰ 2.35‰	Usually adopt impurity more

Table 3. provides with Stellaria 14 kind of plant and extracts the compositions yield relatively:

Among table 3. embodiment 1 from Stellaria not kindred plant extract compositions yield relatively

Numbering	Plant variety	The medicine color and luster	Yield (bright grass meter)	Remarks
					1 2 3 4 5 6 7 8 9 10 11 12	Herba stellariae mediae Herba stellariae mediae north, Anhui Herba stellariae mediae China Herba stellariae mediae southwest Herba stellariae mediae Stellaria dianthifolia Williams Stellaria diversiflora Maxim. Stellaria henryi williams Stellaria maximowixziana Franch. Stellaria micrantha Hayata goose intestinal Herba stellariae mediae Stellaria wushanensis Williams	The dark-brown dark-brown, dark red dark-brown, the brown dark-brown dark-brown of blackout brownish black, the brown little yellowish-brown red dark-brown of obfuscation burgundy, it is brown to turn black	2.19‰ 2.68‰ 2.12‰ 2.30‰ 2.16‰ 2.35‰ 2.08‰ 2.19‰ 2.60‰ 2.43‰ 2.37‰ 1.99‰	Quality is better

3, the preparation embodiment of various dosage forms is as follows:

3.1. injection: the medicine highly finished product 200g that the embodiment extraction separation is obtained dissolves back centrifugal 5 minutes of centrifuge (4000r/min) with 0.9% sodium chloride injection 2000ml, the gained supernatant of centrifugal back is filtered in sterilized clean container through the sealing of 0.5 μ m filter membrane, use in the ampoule in injection through the filling and sealing machine fill, be distributed into respectively optionally that 1ml/ props up 1000,0.1g/ prop up, 450 of propping up of 2ml/, 0.2g/ prop up, and promptly get injection through cobalt 60 radiation sterilizations again.

3.2. injectable powder: the medicine highly finished product 200g that the embodiment extraction separation is obtained dissolves after centrifugal 5 minutes of centrifuge (4000r/min) with distilled water 50ml, the gained supernatant of centrifugal back is filtered in sterilized clean container through the sealing of 0.5 μ m filter membrane, the spray of spray-dried machine is dried to become medicated powder, be potted in the ampoule through filling and sealing machine again, promptly can be made into the injectable powder of 2ml again through cobalt 60 radiation sterilizations, amount to 2000,100mg/ props up.Use with sterilized water for injection dissolving back during use.

3.3. aerosol: get 4g medicine highly finished product add 0.9% sodium chloride injection 100ml dissolving, centrifugal, filter in the 10ml of cleaning dress aerosol bottle, promptly make 10 aerosols, 200mg/ props up.Can be used as the antiviral disinfectant in oral cavity.

3.4. contain tablet: the dressing, spice, correctives etc. one of getting the medicine highly finished product 100g that makes by embodiment 1 and tablet is reinstated tablet machine and is made 2000 of buccal tablets, the 50mg/ sheet.Can be used as the antiviral disinfectant in oral cavity, health food or antiviral functional food.

3.5. capsule: be ground into powdered highly finished product 100g under aseptic condition after getting the medicine vacuum drying that makes by embodiment 1, fill becomes 1000 capsules, the 100mg/ capsule.Can be used for treating various virosiss, also can be used as the antiviral disinfectant in oral cavity, health food or antiviral functional food.

3.6. microcapsule: the medicine dry powder 3g that gets the process refinement treatment that makes by embodiment 1 makes and is suspended in the 3.6g liquid Paraffin; Get I hundred glue 10g more in addition and add distilled water 200ml, boil half an hour with disruptive oxidation enzyme after waiting to dissolve, warm liquid Paraffin is injected my hundred glues, emulsifying is 1～2 minute in tissue mashing machine, makes oil in water emulsion.Get gelatin 10g again and add distilled water 200ml, place in 60 ℃ of water-baths and dissolve, and be mixed in the 1000ml beaker, keep glue, stir at a slow speed at 45 ℃～50 ℃ with above-mentioned my hundred glues.Add in the glue with freshly prepared 5% acetum 5ml, the pH value of regulator solution produces cohesion to being about 4.1.Inject distilled water 750ml behind the encystation, move in the ice bath again and cool off, be cooled to 5～10 ℃, the gelatin cyst membrane is congealed.At this moment microcapsule is spherical.Adding 37% formaldehyde 7ml again is cured.Stirred 15 minutes, and made the microcapsule typing.Regulate capsule liquid to the PH8.0 with 20% sodium hydroxide solution then.After low temperature stirs 1 hour, filter with centrifuge, washing is to neutral formaldehydeless flavor.Add capsule again and weigh 3% magnesium stearate and make diluent, cross 16 mesh sieves behind the mix homogeneously, 50 ℃ of vacuum dryings again, the microcapsule of this medicine, yield 72.2%, meter 16.6g microcapsule, 180mg/g.

3.7. nasal drop: will dissolve back centrifugal 5 minutes of centrifuge (4000r/min) with 0.9% sodium chloride injection 100ml by the medicine highly finished product 2g that embodiment 1 extraction separation obtains, the gained supernatant of centrifugal back filtered in sterilized clean plastics eyedrops bottle through the sealing of 0.5 μ m filter membrane be distributed into 10 nasal drop, 200mg/ props up.

3.8. membrane: get the medicine highly finished product 30g, the azone 0.3ml that make by embodiment 1 add water 100ml dissolving back centrifugal, through 0.5 μ m membrane filtration in clean container, add the suitable heated and stirred of PVA (05-88) 19.5g and make its dissolving, on plate glass, paint wide 100mm under the cleaning condition, be about the medicine film of 100mm, thick about 0.1mm.Lucifuge coating film with wide about 100mm, long 100mm, thick about 0.05mm respectively covers one deck as coating membrane at medicine film upper and lower surface again, is packaged into membrane then.Its dosage is 0.3g/cm ², face the time spent on demand and dosage shear to use.

3.9. mucilage: get Pseudobulbus Bletillae (Rhizoma Bletillae) colloid (medium powder) 2g and be sub-packed in the dry glass bottle of 10 15ml, each adds glycerol 2ml and makes dispersant, after jolting is uniformly dispersed, other gets the stirring of chloroform water 100ml adding 3g medicine highly finished product and makes its dissolving, centrifugal after 0.5 μ m filter membrane filters respectively in finely dispersed Pseudobulbus Bletillae (Rhizoma Bletillae) Plexiglas's bottle, fierce jolting gets the medicine mucilage, the 200mg/ bottle.

3.10. water preparation or nasal drop: the medicine dry powder 10g that gets the refinement treatment that makes by embodiment 1 makes and is dissolved in the 250ml water, can be distributed into 25 bottles of water preparations, the 400mg/ bottle.

3.11. liquid chewing gum: in water preparation, add spice, correctives etc. and make the liquid chewing gum, can be used as oral cavity antiviral disinfectant, antiviral health food or functional food etc.

3.12. chewing gum: 100g chewing gum glue, 0.1ml Oleum menthae spice, pentose 1g make chewing gum as correctives etc. and can be used as oral cavity antiviral disinfectant, antiviral health food or functional food etc.

4, compositions is as the safety of medicinal application

4.1, the acute toxicity testing of compositions mice oral administration:

Summary: the experimental result of mice oral administration shows in one day that it is 32g (dry powder)/kg that double filling stomach gives mice compositions maximum dosage-feeding, is equivalent to 1916.17 times of clinical consumption per day; Observed 7 days continuously, do not find that the toxic reaction and the phenomena of mortality appear in animal.Showing that compositions toxicity is very low, is safe by drafting that clinical dosage takes.

4.1.1, test objective:

Observation once or after giving mice compositions saturated solution for several times, acute toxic reaction that experimental animal produced and death condition are for clinical consumption provides reference frame.

4.1.2, test material:

4.1.2.1, animal: healthy regular grade Kunming mouse, body weight 18～22g, male and female half and half are provided by Anhui Prov. Medical Science Inst.'s laboratory animal laboratory.The quality certification: No. 01, the real moving accurate word of Anhui doctor.

4.1.2.2, medicine: composition powder, lot number: 050224; Provide by Mr. Zhu Gengxin, be mixed with desired concn with distilled water before using.

4.1.3, test method:

4.1.3.1, trial test:

The saturated solution of composition powder (400mg/ml): get 12 of white mice, fasting 14～16 hours, body weight 19-21 gram, male and female half and half.Look sex and body weight animal is divided into 3 groups at random, 4 every group, the agent distance was than 1: 0.5 between group.Each treated animal is irritated the solution (400mg/ml, 200mg/ml, 100mg/ml) that stomach gives composition powder with the 0.4ml/10g body weight respectively, observes oral being subjected in one week of reagent, causes the fatal dose of laboratory animal 0% and 100% death and the symptom that animal is showed.Result: after 3 treated animals are taken medicine, all find no animal poisoning symptom and death condition take place, so adopt the maximum dosage-feeding test.

4.1.3.2, maximum dosage-feeding test (MTD):

Composition powder: get 20 of mices, male and female half and half, body weight 18～20g.In 24 hours, be administered twice (twice dosing interval is 6 hours) for respectively each Mus continuous irrigation stomach, irritate stomach at every turn and give composition powder saturated solution (400mg/ml) 0.8ml/20g, accumulative total gavages 1.6ml, instant rising observed mice poisoning and death condition, observes continuously 7 days.

4.1.3.3, result of the test:

(1). test mice body weight change situation:

In the week, all do not have the death of appearance behind the sample sets animals administer, the activity of animal, the mental status, diet, defecation etc. there is no unusually.The mice body weight change sees Table 4. respectively when testing preceding and off-test:

Table 4. composition powder acute toxicity test mice body weight change (X ± S)

Sex	Body weight (g) before the experiment	Body weight (g) after one week
			Female male	18.7±0.82 18.9±0.74	24.3±1.11 25.8±1.01

(2). the maximum dosage-feeding of composition powder calculates:

The mice maximum tolerated dose: the compositions saturated solution contains 400 milligrams of composition powders for every milliliter, and the mice average weight is 20g, irritates stomach volume 0.8ml at every turn, amounts to 2 times.Mice day oral compositions powder maximum tolerated dose=1.6ml * 0.4g/ml/0.02kg=32g/kg

Margin of safety: 60kg is a standard with adult's average weight, and the consumption per day of composition powder is 1g.The mice average weight is 20g, and a day maximum dosage is 1.6ml * 0.4g/ml.

Margin of safety=0.64g/20g ÷ 1g/60000g=1916.17 (doubly)

4.1.3.4, conclusion:

Above-mentioned data show that acute toxicity test does not see that overt toxicity etc. is arranged in the animal body of composition oral administration, so compositions is a kind of very safe natural drug.

Composition powder mice oral administration, maximum tolerated dose is 32g/kg, than the inventor once in CN1377680A and two parts of patents of CN 1498630A disclosed oral administration maximum tolerated dose be better about 3 times of 11.25g/kg, be equivalent to 1916.17 times of clinical administration daily dose.The experimental result explanation: composition powder does not produce the overt toxicity reaction under animal oral administration condition, sample sets laboratory animal body weight natural increase during the laboratory observation, activity, the mental status, diet and defecation etc. are not seen obvious change yet, showing that compositions toxicity is lower, is safe by drafting that clinical dosage takes.

5, experiment of the general pharmacology of compositions nasal drop and result thereof:

5.1, to the neural influence of mice and rat spirit,

5.1.1, the compositions nasal drop is to the neural influence of mice and rat spirit,

5.1.1.1, to the influence of the sleeping number of mice:

Get 100 of KM mices, body weight 18-22g, male and female half and half are divided into 5 groups at random, i.e. (1) normal control group: the equal-volume distilled water; (2) pentobarbital sodium+distilled water group: 1ml/kg; (3) pentobarbital sodium+compositions nasal drop I group: 0.16g/kg; (4) pentobarbital sodium+compositions nasal drop II group: 0.33g/kg; (5) pentobarbital sodium+compositions nasal drop III group: 0.67g/kg.Each group is all distinguished intranasal administration by the volume of 1ml/kg.Except that the normal control group, respectively organize under the lumbar injection threshold pentobarbital sodium 25mg/kg of sleep dosage behind the 15min, observe and record injection pentobarbital sodium 30min in the number (reach with the mice righting reflex loss person reacts as sleeping more than 1 minute) of every group of sleeping mice.The results are shown in Table 5:

Table 5 compositions nasal drop is to the influence of the sleeping number of elements of mice

Group	Dosage g/kg	Number of animals	Sleeping number of elements	Sleeping rate (%)
					Normal control group pentobarbital sodium group compositions nasal drop I group compositions nasal drop II group compositions nasal drop III group	1ml/kg 1ml/kg 0.16 0.33 0.67	20 20 20 20 20	0 1 1 2 2	0 5 5 10 10

Experimental result shows that three dosage groups of compositions nasal drop do not have synergism to sleep dosage under the mice pentobarbital sodium threshold, compares with the pentobarbital sodium group, and there was no significant difference (P＞0.05), prompting compositions nasal drop does not have syngignoscism to mice.

5.1.1.2, the compositions nasal drop is to the influence of spontaneous activity in mice:

Get 40 of the Kunming mouses of body weight 18～22g, male and female half and half are divided into 4 groups at random: i.e. (1) matched group: the equal-volume distilled water; (2) compositions nasal drop I group: 0.16g/kg; (3) compositions nasal drop II group: 0.33g/kg; (4) compositions nasal drop III group: 0.67g/kg.Each group is all distinguished intranasal administration by the volume of 1ml/kg.With 15min, 30min, 45min, 60min, 90min spontaneous activity situation after the administration of toy analyzer observation mice, movable number of times in the record mice 5min.The results are shown in Table 6:

Table 6 compositions nasal drop to the influence of mice activity count (

N=10)

Group	Dosage (g/kg)	Activity count (number of times/5min)
								Before the medicine	15min	30min	45min	60min	90min
		Matched group compositions nasal drop I group compositions nasal drop II group compositions nasal drop III group	---- 0.16 0.33 0.67	25.1±7.3 24.8±8.4 22.6±8.8 24.4±7.6	20.6±10.3 19.5±8.8 21.5±9.8 25.7±6.2	18.6±8.2 23.8±7.9 18.9±9.8 24.3±9.6	17.5±7.0 20.1±13.5 20.5±8.4 23.3±5.0							18.6±9.7 16.5±9.3 18.6±9.4 20.3±6.0	26.1±10.0 23.0±8.5 22.6±12.3 24.8±9.0

Experimental result shows, the mice activity count of each dosage group of compositions nasal drop 15min, 30min, 45min, 60min, 90min after administration, compare there was no significant difference (P＞0.05) with matched group, prompting compositions nasal drop does not have influence to the central nervous system of mice.

5.1.1.3, on transfer rod, the drop influence of number of times of rat

Screen 40 of qualified SD rats (after 1 adaptation, rat stops 3 minutes persons at least as qualified rat on transfer rod), male and female half and half are divided into 4 groups at random, i.e. (1) matched group: isopyknic distilled water; (2) compositions nasal drop I group: 0.08g/kg; (3) compositions nasal drop II group: 0.16g/kg; (4) compositions nasal drop III group: 0.33g/kg.Each group is all by the volume intranasal administration of 1ml/kg.Respectively after administration 15,30,45,60, during 90min, observe the number of times that drops in the rat 5min.The results are shown in Table 7:

Table 7 compositions nasal drop to rat on transfer rod, drop times influence (

N=10)

Group	Dosage (g/kg)	Drop number of times (inferior/5min)
								Before the medicine	15min	30min	45min	60min	90min
		Matched group compositions nasal drop I group compositions nasal drop II group compositions nasal drop III group	-- 0.08 0.16 0.33	0 0 0 0	0.2±0.4 0.2±0.4 0.5±0.5 0.4±0.5	0.4±0.5 0.3±0.5 0.3±0.5 0.1±0.3	0.3±0.7 0.1±0.3 0.2±0.4 0.1±0.3							0.3±0.5 0.1±0.3 0.4±0.5 0.3±0.5	0.5±0.5 0.2±0.4 0.2±0.4 0.3±0.5

The result shows, three dosage groups of compositions nasal drop 30min, 45min, 60min, 90min, 120min different time sections rat transfer rod after the administration number of times that drops, compare there was no significant difference (P＞0.05) with matched group, prompting compositions nasal drop is to the not influence of behavior of rat.

5.1.1.4, conclusion

(1) compositions nasal drop 0.67g/kg, 0.33g/kg, 0.16g/kg three dosage groups do not have synergism to sleep dosage under the mice pentobarbital sodium threshold, relatively do not have significant difference (P＞0.05) with the pentobarbital sodium group, prompting compositions nasal drop does not have syngignoscism to mice.

(2) compositions nasal drop 0.67g/kg, 0.33g/kg, 0.16g/kg each dosage group different time sections after administration compares there was no significant difference (P＞0.05) to the spontaneous activity counting of mice with matched group, prompting compositions nasal drop does not have influence to the central nervous system of mice.

(3) compositions nasal drop 0.33g/kg, 0.16g/kg, each dosage group of 0.08g/kg different time sections rat transfer rod after the administration number of times that drops does not relatively have significant difference (P＞0.05) with matched group, and prompting compositions nasal drop is to the not influence of behavior of rat.

In sum, the compositions nasal drop is to the movable not influence of the normal behaviour of rat, mice, with threshold down the pentobarbital sodium of sleep dosage do not have synergism, showing that the compositions nasal drop does not have obviously the spiritual nervous system of animal in being subjected to the amount of reagent scope influences.

5.2, the compositions nasal drop is to the influence of anesthetized dog cardiovascular and respiratory system

5.2.1, method and observation index, observing time and statistical disposition:

Tried hybrid dog fasting 24 hours, freely drunk water.Pentobarbital sodium (30mg/kg, iv) after the anesthesia, femoral arteriography links to each other with eight road physiology monitors through pressure transducer, remembers blood pressure (systolic pressure, diastolic pressure, mean arterial pressure), heart rate fully; Breathing zone is surveyed breathing at the xiphoid-process place through transducer; Needle electrode penetrates into the accurate II lead electrocardiogram of subcutaneous mark.Operation is finished, and treats intranasal administration behind each parameter stability, observes every index.

1. observation index: cardiovascular system: observe systolic pressure, diastolic pressure, mean arterial pressure, heart rate, the rhythm of the heart etc.Respiratory system: observe respiratory frequency and amplitude of respiration.

2. grouping, dosage and observing time: laboratory animal is divided into 4 groups at random, several 5 of every treated animal, and male and female are regardless of.

(1) matched group: give the isometric(al) distilled water;

(2) compositions nasal drop low dose group gives: 0.16g/kg;

(3) the dosage group gives in the compositions nasal drop: 0.33g/kg;

(4) compositions nasal drop high dose group gives: 0.67g/kg.

Each group all by 0.4ml/ once through intranasal administration.

Observing time be before the administration and administration after 5,15,30,45,60,90,120min.

3. statistical disposition

All data informations adopt Student ' s-t check.

Measured value before Δ %=(after the administration not phase measured value-administration simultaneously before measured value)/administration * 100%

5.2.2, result of the test

The result shows: the basic, normal, high dosage group of compositions nasal drop does not have obviously the blood pressure that is tried anesthetized dog to be influenced, and does not relatively have significance statistical significance (P＞0.05) with matched group.Three dosage groups to the heart rate that tried anesthetized dog, electrocardiogram does not have obviously influences, and does not relatively have significance statistical significance (P＞0.05) with matched group.

Three dosage groups of compositions nasal drop do not have obviously the respiratory frequency of being tried anesthetized dog and amplitude to be influenced, and does not relatively have significance statistical significance (P＞0.05) with matched group.

6, compositions is as the enforcement of antiviral drugs application

6.1, compositions has better wide spectrum preventing respiratory viruses usefulness

6.1.1, the experimentation of resisiting influenza virus in the mice Orally administered composition body

6.1.1.1, the pure Chinese medicine extract of combination of compositions system, for studying the effect of its resisiting influenza virus, adopt influenza infection mice viral pneumonia model, resisiting influenza virus effect in the Orally administered composition body is studied.

The inventor discloses the application as antiviral drugs of the total organic phenolic acid that contains element sulphur from Stellaria plant Herba stellariae mediae or other a kind of Stellaria plant in the molecular structure that extracts and glucosides class or high polarity compound compositions such as total flavones and glucosides class thereof thereof in CN 1377680A and two parts of patents of CN 1498630A, comprise that test cell line proof compositions can be to adhering to the influenza virus of RNA class separately, parainfluenza virus, rhinovirus, Echovirus, herpesvirus has stronger inhibitory action with the two big class Respiroviruses such as adenovirus that belong to the DNA class, particularly to influenza virus, parainfluenza virus and adenovirus 3 have powerful inhibition, therefore have unique broad-spectrum antiviral performance.Its nasal drop is resisiting influenza virus FM in the mice animal body ₁Result of the test show 50% mice protective rate (ED ₅₀) be 0.51mg/kg, the interior therapeutic index has powerful resisiting influenza virus effect up to proof compositions more than 4500.

This open composition oral administration resisiting influenza virus FM in the mice animal body ₁Result of the test because medicine is subjected to the influence etc. of digestive tract and liver first-pass effect behind the oral administration, so its therapeutic index ought to be lower than the therapeutic index of nasal drop administration, but it reaches when keeping clinical effectiveness and uses purpose more easily.

6.1.1.2, material and medicine

6.1.1.2.1, the animal Kunming mouse, body weight 18～22g, male and female half and half, female unpregnancy.

6.1.1.2.2, medicine is subjected to reagent: compositions dry powder, lot number: 050224, provide by Mr. Zhu Gengxin.Each administration group dosage of sampling test animal is 128mg/kg, 64mg/kg, 32mg/kg and 16mg/kg (pressing body surface area calculates), is equivalent to 6 times, 3 times, 2 times and 1 times of the clinical consumption per day of people respectively.Positive control drug: SHUANGHUANGLIAN KOUFUYE, Harbin Pharmaceutical Group's three smart pharmaceutcal corporation, Ltd products, specification: 10ml/ props up, lot number: 03051841, the experimental animal dosage is 9ml/kg (pressing body surface area calculates), is equivalent to 9 times of clinical day use amount of people.Ribavirin, Sichuan Mei Dakang pharmaceutcal corporation, Ltd product, specification: 100mg/ sheet, lot number: 030212.The experimental animal dosage is 106mg/kg (pressing body surface area calculates), is equivalent to 9 times of clinical day use amount of people.Above medicine all is mixed with desired concn with distilled water before use.

6.1.1.2.3, the suitable strain (FM of viral influenza virus A 1 type Mus lung ₁), draw from national influenza center, by this institute virus research chamber preservation strain that goes down to posterity.Hemagglutinative titer E=1: 1280.

6.1.1.3, method and result

6.1.1.3.1, FM ₁Increase poison and preserve

Get 9 age in days chick embryo allantoic cavities inoculation FM ₁Seed culture of viruses liquid, 34 ℃ of conventional cultivations, 48 hours collection allantoic fluids.Collect the allantoic fluid of hemagglutinative titer＞1: 1280 with the Microhemagglutination method, the tubule packing, it is standby to put-70 ℃ of refrigerators.

6.1.1.3.2 the mensuration (LD of influenza virus Mus lung adapted strain virulence ₅₀)

Get 30 of regular grade Kunming mouses, body weight 18～22g, male and female half and half, female unpregnancy.View volume is heavy to be divided into 5 groups with sex with the mice stratified random, and 6 every group, wherein male and female are each 3.Under the absolute ether light anaesthesia, use FM ₁50ul/ collunarium infecting mouse of the suitable influenzae strain virus liquid of Mus lung, each dilution factor of organizing mouse infection virus is respectively 1,10 ^-1, 10 ^-2, 10 ^-3, 10 ^-4After the mouse infection virus, observe and write down each treated animal death toll day by day, observed continuously 14 days.According to the dead sum of each treated animal, press the median lethal dose(LD 50) (LD that the Reed-Muench method is calculated mouse infection virus ₅₀).

The results are shown in Table 8. animal dead percentage rate computer charts

Table 8. animal dead percentage rate computer chart

The viral dilution degree	Mus lives	Dead Mus	The accumulation and		Dead ratio	Per cent death loss
							Mus lives	Dead Mus	Infect number/death toll
			1 10 -1 10 -2 10 -3 10 -4	0 3 4 6 6	6 3 2 0 0					0 3 7 13 19	11 5 2 0 0	▲11/11 * 5/8 2/9 0/13 0/19	100％ 62.5％ 22.22％ 0％ 0％

^*Denominator is infecting mouse sum (comprising dead, alive Mus) ^▲Molecule is dead number of mice

As seen from Table 8: the mortality rate of each dilution factor infecting mouse is respectively 100%, 62.5%, 22.22%, 0% and 0%., can make the dilution factor of half infecting mouse death should be 10 ^-1～10 ^-2Between.Calculate LD in view of the above ₅₀Value.

The first step: distance proportion=＞50% per cent death loss-50/＞50% per cent death loss-＜50% per cent death loss by formula, in will showing with LD ₅₀(55%) and following (22%) adjacent several substitution formula are tried to achieve distance proportion number=62.5-50/62.5-22.22=0.31 on the value

Second step: the logarithm with the viral dilution degree of＞50% animal dead, add the distance proportion number, multiply by the logarithm of the coefficient of dilution again, promptly try to achieve LD ₅₀Value.The logarithm of the viral dilution degree of＞50% animal dead is 10 ^-1

LD ₅₀=1+0.31 * 1 (logarithm of the coefficient of dilution 10)=1.31

According to result of calculation, try to achieve the mice collunarium and suck infection FM ₁LD ₅₀Be 10 ^-1.31

6.1.1.3.3, compositions is to the therapeutical effect of influenza infection induced mice viral pneumonia

Get 80 of regular grade Kunming mouses, body weight 18～22g, male and female half and half.Press dosage shown in the table 1, the apparent motion rerum natura not and body weight the mice stratified random is divided into 8 groups, 10 every group, male and female half and half.Under the absolute ether light anaesthesia, with 5 times of LD ₅₀Suck and infect 7 groups of mices with batch Embryo Gallus domesticus seed culture of viruses influenza virus liquid 50ul collunarium that goes down to posterity, the normal control group splashes into the equivalent normal saline solution.Each administration treated animal gives gastric infusion in the time of viral infection, every day 2 times, and each 0.4ml/20g body weight, successive administration 6 days, normal control group and virus control group are all irritated stomach and are given the isometric(al) distilled water.From the self-infection virus, observe and write down each experimental group dead animal number day by day, observed continuously 14 days.Sum with every treated animal death in 14 days calculates mortality rate (survival rate), dead protective rate and mean survival time by following formula.Mortality rate (survival rate)=survival (death) number/laboratory animal number * 100%; Dead protective rate (%)=(matched group mortality rate-experimental group mortality rate) * 100%; Every animal survival number of days addition/laboratory animal number in The average survival time day=on the same group; Prolong vital rates (%)=(experimental group on average survive natural law-matched group on average survive natural law)/matched group natural law * 100% of on average surviving.X ², t check comparable group differences.The results are shown in Table 9., table 10.:

Table 9. composition solution is to the influence of the dead protective rate of influenza virus infecting mouse

Number of times	Group	Dosage mg/kg * d	Death toll/number of animals	Mortality rate %	Dead protective rate %
						1	Normal control papova matched group SHUANGHUANGLIAN KOUFUYE ribavirin tablet composition liquid	- - 9ml×6 106×6 12.5×6 25.0×6 50.0×6 100×6	0/12 12/12 10/12 8/12 6/12 4/12 3/12 2/12	- 100 83.33 66.67 50.00 33.33 25.00 16.67	- - 16.67 33.33 50.00 66.67 75.00 83.33
2	Normal control papova matched group SHUANGHUANGLIAN KOUFUYE ribavirin tablet composition liquid	- - 9ml×6 106×6 16×6 32×6 64×6 128×6	0/12 12/12 8/12 7/12 7/12 5/12 3/12 2/12	- 100 66.67 58.33 58.33 41.67 25.00 16.67	- - 33.33 41.67 41.67 58.33 75.00 83.33

Table 10. composition solution is to the influence of influenza virus infecting mouse mean survival time

Number of times	Group	Dosage mg/kg * d	Survival number/animal number of elements	Survival rate %	The average survival time day X ± S	Prolong vital rates %
							1	Normal control papova matched group SHUANGHUANGLIAN KOUFUYE ribavirin tablet composition liquid	- - 9ml×6 106×6 16×6 32×6 64×6 128×6	12/12 0/12 2/12 4/12 6/12 8/12 9/12 10/12	- - 16.67 33.33 50.00 66.67 75.00 83.33	＞14.0±0 5.08±1.16 ▲▲ 8.5±3.03 ** 10.17±3.10 ** 9.08±3.15 ** 9.88±3.25 ** 10.39±3.15 ** 10.88±3.25 **	- - 67.32 100.20 78.74 100.23 100.43 100.65

2

Normal control papova matched group SHUANGHUANGLIAN KOUFUYE ribavirin tablet composition liquid

- - 9ml×6 106×6 16×6 32×6 64×6 128×6

10/12 0/12 2/12 5/12 5/12 7/12 9/12 10/12

- - 16.67 41.67 41.67 58.33 75.00 83.33

＞14.0±0 5.2±0.92 ▲▲ 8.6±3.34 * 10.2±2.94 ** 8.91±2.77 * 9.56±3.35 ** 10.39±3.15 ** 10.88±3.28 **

- - 65.38 96.15 96.15 100.15 100.43 100.65

Compare with normal group: ^{▲ ▲}P＜0.01; Compare with the virus group: ^*P＜0.05, ^*P＜0.01

Table 9 shows with table 10 result: virus control group mice is substantially all dead about 5 days behind the viral infection, and after giving the composition solution of various dose, all can reduce the mortality rate of infecting mouse, make and obviously prolong infection animal The average survival time day (very remarkable) with 128mg/kg, 64mg/kg dosage group.Its effect can strengthen along with the increasing of dosage within the specific limits.Compare with the virus control group, remarkable statistical significance is arranged.Composition solution 64mg/kg, 128mg/kg dosage group reduce the mortality rate of infecting mouse and prolong its mean survival time effect close with ribavirin tablet, obviously are better than the SHUANGHUANGLIAN KOUFUYE group.

6.1.1.3.4, compositions causes mice viral pneumonia model pneumonopathy to influenza infection and becomes influence:

Get 80 of healthy regular grade Kunming mouses, body weight 18～22g, male and female half and half.Press dosage shown in the table 11, the apparent motion rerum natura not and body weight the mice branch deposited be divided into 8 groups at random, 10 every group, male and female half and half.Under the absolute ether light anaesthesia, with 5 times of LD ₅₀Suck and infect 7 groups of mices with batch Embryo Gallus domesticus seed culture of viruses influenza virus liquid 50ul collunarium that goes down to posterity, normal control group collunarium sucks the equivalent normal saline.Each administration treated animal gives gastric infusion respectively in viral infection, every day 2 times, and the each 0.4ml/20g body weight of administration volume, successive administration 4 days, normal control group and virus control group are all irritated stomach and are given the isometric(al) normal saline.Infection animal is isolated nursing, freely ingests drinking-water.After the last administration 1 hour, the animal back of weighing is fixing, cut off skin of chest, cut off left oxter arterial blood letting and put to death animal.The mice thoracic cavity is opened in dissection, takes out full lung, after the lymphoid tissues such as rejecting trachea and hilus pulumonis, blots the lungs surface liquid with filter paper, puts balance to weigh, and heavily calculating the lung exponential sum one by one divided by body weight respectively organizes lung index suppression ratio by lung.With t check comparable group differences.Leave and take lung tissue sample, carry out tectology and observe and take the photograph sheet.The results are shown in Table 11..

Table 11 composition solution is to the pathogenic toxicity pneumonia lung index influence of influenza virus infecting mouse

Group	Dosage mg/kg * d	Number of animals only	Lung index g/100g	Lung index suppression ratio %	The P value
						The normal control group		10	0.93±0.13

Virus control group composition solution SHUANGHUANGLIAN KOUFUYE ribavirin tablet

16×4 32×4 64×4 128×4 9ml×4 106×4

10 10 10 10 10 10 10

1.60±0.26 ▲▲ 1.28±0.20 * 1.22±0.23 * 1.16±0.14 ** 1.08±0.19 ** 1.32±0.21 * 1.19±0.10 **

19.89 23.25 25.83 30.25 17.5 25.63

P＜0.01 P＜0.05 P＜0.01 P＜0.01 P＜0.01 P＜0.05 P＜0.01

^{▲ ▲}Compare with normal group; ^*Compare with the virus group

By table 11 result as seen: compare with normal group, the lung index of virus control group mice obviously increases, and statistical significance is extremely remarkable.After giving the composition solution of various dose, infection animal lung weight in wet base index all is starkly lower than virus control group (P＜0.01～0.05), and its therapeutic effect can be along with the increase of drug dose, and the lung exponential quantity also reduces accordingly, presents better correlation.Composition solution 128mg/kg, 64mg, 32mg/kg dosage treated animal therapeutic effect are better than ribavirin tablet, significantly are better than the SHUANGHUANGLIAN KOUFUYE group.

6.1.2, oral administration is used in influenza patient's clinical practice effect:

Get the compositions of 1.32g and load into 6 of capsules with No. 1 capsule, each oral one, can in 1 day half, cure a routine influenza patient every day 3 times, the fastest only needs to cure half a day.The viral influenza of clinical personal treatment has 100 many cases time over 2 years, no matter is which day in the influenza course of disease, in case used compositions about 1～2 two day, control clinical symptoms and then reached the purpose of curing influenza, but and operate as normal with learnt; Comprise that the back of taking medicine can eliminate headache in more than ten minute to 30 minutes fully, then stuffy nose relieving, eliminate clear nasal mucus, tear and symptom such as pain from head to foot, brought down a fever in 36 hours at 24 hours.The early stage result of use of falling ill is good more, the fastest case once morbidity that night (headache, from head to foot pain, 39.5 ℃, drop tears, nasal mucus etc.) use medicine just before going to bed one time, only 1, be that operate as normal has been learnt the next morning.Compositions prevents and treats viral influenza to reach efficient even specific drug degree.

6.2, the animal vivo test and the result thereof of oral and intravenous administration show that also compositions can obviously reduce hepatitis B virus DNA in the animal body, also has obvious inhibition effect to hepatitis virus:

6.2.1, material and method

6.2.1.1, medicine: compositions is prepared with normal saline by the pale brown color medicated powder that Mr. Zhu Gengxin provides.

Positive control medicine lamivudine is by the plain Kang Wei of Ge Lan drugmaker product, and lot number: B008923 prepares with normal saline.

6.2.1.2, virus:

Duck b hepatitis virus dhbv dna DNA (DHBV-DNA) strong positive serum ,-70 ℃ of preservations.

6.2.1.3, animal:

1 age in days Beijing duck is available from progressive species duck animal feeding field, Beijing.

6.2.1.4, reagent:

α ^-32P-dCTP is available from the auspicious biotechnology of Beijing good fortune engineering company, and the nick translation medicine box is available from Pu Luomaige company (Promega Co.); Sephadex G-50, Ficoll PVP is available from Sweden Pharmacia company; SDS West Germany Merck company product; Milt DNA, bovine serum albumin are that Instite of Biophysics, Chinese Academy of Sciences produces; Nitrocellulose filter 0.45 μ m Amersham produces.

6.2.2, experimental technique:

6.2.2.1, duck hepatitis B virus infection:

1 age in days Beijing duck is clear through the positive Sanguis Anas domestica of lower limb shin intravenous injection Shanghai sheldrake DHBV-DNA, and every 0.2ml got blood in back 7 days in infection, separation of serum, and-70 ℃ of preservations are to be checked.

6.2.2.2, Drug therapy test:

DHBV infect duckling after 7 days random packet carry out the Drug therapy test, 6 every group, 2 dosage groups of administration component, oral administration is respectively 250mg/kg and 500mg/kg, the intraperitoneal injection group is respectively 25mg/kg and 50mg/kg group, 1 day 2 times, administration 10 days.

If virus control group (DHBV) is with the physiologic saline for substitute medicine.The positive drug lamivudine, oral administration 50mg/kg, 1 day 2 times, administration 10 days.

The 7th day is (TO) before the medication after infection, and medication the 5th day (T5) after medication the 10th day (T10) and the drug withdrawal the 3rd day (P3), is got blood from duck lower limb shin vein, and separation of serum is to be checked in-70 ℃ of preservations.

6.2.2.3, detection method:

It is clear to get above-mentioned Sanguis Anas domestica to be checked, every batch with the time point film, measure the dynamic of the clear middle DHBV-DNA level of Sanguis Anas domestica, press nick translation medicine box description method,, and make the clear dot blot hybridization of Sanguis Anas domestica with 32P labelling DHBV-DNA probe, autoradiography diaphragm speckle, measure OD value (optical filter is 490nm) at enzyme mark detector, calculating serum DHBV-DNA density, with hybridization spot OD value as specimen DHBV-DNA level value.

6.2.2.4, drug effect calculates:

6.2.2.4.1, calculate the meansigma methods (X ± SD) of every group of duck different time serum DNA OD value, and with (T0) OD value comparison before the 3rd day (P3) serum DHBV-DNA level after different time (T5, T10) and the drug withdrawal after every group of duck medication and the administration on the same group, adopt paired t-test, meter t1, P1 value.Analyze the significance of difference, judge the inhibition effect of medicine viral infection.

6.2.2.4.2, calculate after every group of duck medication the 3rd day (P3) serum DHBV-DNA suppression ratio behind the different time (T5, T10) and drug withdrawal, the dynamic of the clear DHBV-DNA suppression ratio of Sanguis Anas domestica respectively organized in and mapping.

6.2.2.4.3, with identical with the virus control group respectively time D HBV-DNA suppression ratio of drug treatment group different time DHBV-DNA suppression ratio relatively, adopt t check in groups, take statistics to learn and handle, calculate t2, P2 value, analyze the significance of difference, the judgement drug effect.

6.2.2.5, the result:

6.2.2.5.1, after 1 age in days Beijing crow infects DHBV, serum DHBV-DNA is dynamic

The DHBV-DNA results of dot sees Table 1 behind the DHBV-DNA infected duck oral normal saline.36 serum DHBV-DNA of experimental infection duck total positives.6 ducklings of virus control group infect the 7th day serum DHBV-DNA total positives in back, test in omnidistance 21 days steady substantially behind the serum DHBV-DNA level infection.

6.2.2.5.2, resistive medicine lamivudine is to the influence of DHBV-DNA

The oral positive drug lamivudine of DHBV infected duck 50mg/kg, 1 day 2 times, administration 10 days.The results are shown in Table 1, table 2.Pair analysis, the OD value comparison of (TO) before administration the 10th day (T10) and the administration, descending has highly significant (P＜0.01), to serum DHBV-DNA suppression ratio and virus control group, becomes group analysis administration the 10th day (T10) that significant differences (P＜0.01) is arranged after the administration.3 days (P3) not statistically significants have rebound phenomenon after the drug withdrawal.

6.2.2.5.3, compositions in DHBV infected duck body to the experimental result of the influence of the clear DHBV-DNA of Sanguis Anas domestica:

Two kinds of experiment branch oral administration and intraperitoneal injections are selected two dosage groups respectively for use, and oral administration is respectively 100mg/kg, 200mg/kg, 1 day twice, administration 10 days (Bid * 10); Intraperitoneal injection is 15mg/kg, 30mg/kg, and 1 day 2 times, administration 10 days (Bid * 10) is observed medicine to toxicity of duck and the influence of the clear hepatitis B virus DNA of Sanguis Anas domestica (DHBV-DNA) d.

6.2.2.5.3.1, oral administration experiment shows the heavy dose of group of compositions oral administration 200mg/kg, 1 day twice, avirulence, by pairing statistics, after the administration of 200mg/kg group the 5th day, the 10th day, the clear DHBV-DNA of treatment group Sanguis Anas domestica had highly significant descend (P＜0.01).By statistics in groups and matched group separately relatively, after the administration the 5th day, after 10 days and the drug withdrawal 3 days, the clear DHBV-DNA of treatment group Sanguis Anas domestica all had highly significant descend (P＜0.01,0.01).

6.2.2.5.3.2, intraperitoneal injection, heavy dose of group 30mg/kg group, twice administration in 1 day 10 days, by after the administration of pairing statistics the 5th day, the clear DHBV-DNA of treatment group Sanguis Anas domestica promptly had highly significant descend (P＜0.01).Statistics and matched group separately relatively have highly significant descend (P＜0.01,0.01) in groups.15mg/kg group, by the pairing statistics, after the drug withdrawal 3 days, the clear DHBV-DNA of treatment group Sanguis Anas domestica had remarkable decline (P＜0.05).By statistics in groups and matched group separately relatively, after the administration after the 5th day and the drug withdrawal 3 days, the clear DHBV-DNA of treatment group Sanguis Anas domestica had remarkable decline (P＜0.05).

It is its important feature that oral administration and intraperitoneal injection there is no rebound phenomenon.

So the compositions of extracting with scientific method from the Stellaria plant can be used as safety and effectively anti-hepatitis virus medicament application.

6.3, the beneficial effect of compositions also can provide by following 2 reports and clinical practice result:

6.3.1, report 1. test cell lines proof compositions can effectively suppress HIV (human immunodeficiency virus)-1 (HIV-1)

The result:

6.3.1.1, antiviral activity

In vitro tests shows that compositions has the effect of anti AIDS virus (HIV-1), and the result is as follows:

Drug level (mg/ml) 0.20 0.10 0.05 0.025

Suppression ratio (%) 98.58% 64.3400% 23.90% 12.11%

Calculate IC by statistics ₅₀=0.113mg/ml

Positive control drug AZT concentration is when 1g/ml, and suppression ratio is 100%.

6.3.1.2, cell toxicity test result is as follows:

Drug level (mg/ml) 5 2.5 1.25 0.625

Cell mortality (%) 72 40.04 14.88 0

6.3.1.3, calculate TC by statistics ₅₀So=3.235mg/ml is safety index (TC ₅₀/ IC ₅₀) be 29.09.

6.3.2, report 2. test cell lines proof compositions can effectively suppress the result of H 5 N 1 avian influenza type virus.

6.3.2.1, medicine: " compositions " is Herba stellariae mediae extract, and Mr. Zhu Gengxin provides.

6.3.2.2, virus: the H 5 N 1 avian influenza type

6.3.2.3, cell: the human embryonic lung cell

6.3.2.4, the result: what the nontoxic boundary of compositions pair cell was selected the results are shown in Table 12.:

The nontoxic boundary of table 12. compositions pair cell is selected (drug level mg/ml)

The result: compositions is non-toxic concn with 1mg/ml

6.3.2.5, compositions really sees Table 13. to the toxic effect that presses down of H 5 N 1 avian influenza type virus in the test cell line:

Table 13. compositions presses down toxic effect really to adenovirus type III

Its method is: virus is with 100TCID ₅₀Be infective dose, first infection cell monolayer, dosing after 3 hours.

6.3.2.6, conclusion: " compositions " has the effect of strong inhibition H 5 N 1 avian influenza type virus on cell in vitro is cultivated with 1mg/ml concentration.

6.3.3, the actual efficacy of composition oral administration clinical treatment influenza:

6.3.3.1, method:

Compositions is made every tablet of " buccal tablet " that contains compositions 50mg, and per hour containing is 1, administration every day 10 times, two days common administration 1g.

6.3.3.2, the result: " buccal tablet " of set of applications compound treatment 12 routine influenza patients the results are shown in Table 15.:

The clinical example of giving 50mg/ treatment 12 routine influenza patients of compositions " buccal tablet " of table 15.

Name	Sex	Age	Time	Clinical symptoms	The result
						Tang * * high * * woods * * attempt * permitted * * yellow * * turn round and look at * * season * Zhu * * what * Lin * * poplar * *	The women men and women man of men and women men and women	25 35 29 45 48 7 33 27 48 15 36 77	03.1.10 03.1.25 03.3.17 03.12.16 04.1.10 04.1.28 04.2.16 04.11.07 04.12.22 05.2.08 05.2.26 05.11.19	Head reaches pain from head to foot, flow clear nasal mucus, 39.5 ℃ head and pain from head to foot flow clear nasal mucus, 39.8 ℃ of 39.5 ℃ of stuffy nose with watery discharge, 39.5 ℃ of the not high headache snivels of blood phase, the not high mutually head of blood reaches pain from head to foot, flows clear nasal mucus, and 39.5 ℃ of heads reach pain from head to foot, flow clear nasal mucus, 39.5 39.8 ℃ of ℃ stuffy nose with watery discharge, 39.5 ℃ of the not high headache snivels of blood phase, the not high mutually head of blood reaches pain from head to foot, flow clear nasal mucus, 39.5 ℃ head and pain from head to foot flow clear nasal mucus, 39.8 ℃ of 39.5 ℃ of stuffy nose with watery discharge, 39.5 ℃ of the not high headache snivels of blood phase, blood is not high mutually	After 36 hours working after 36 hours working go to school that going to work next day goes to work next day next day and go to school 48 hours next day of fully recovering went to school next day 36 hours after working go to school next day to go to work next day and bring down a fever in 36 hours

6.3.3.3, conclusion: compositions is clinical gives " buccal tablet " treatment 12 routine influenza patients, all can in two days, cure, can bring down a fever and eliminate flu-like symptom in the fastest half a day that only needs, thereby can go to school or go to work, compositions can shorten viral influenza course of treatment more than 5 days at least, therefore, has the function of extraordinary prevention and treatment influenza, it is evident in efficacy to be better than influenza virus neuraminidase inhibitors such as English, beautiful Zanamivir and Oseltamivir, can reach the specific drug degree.

6.3.4, the actual efficacy of compositions clinical treatment herpes simplex and herpes zoster:

6.3.4.1, method: the patient who suffers from herpes simplex and herpes zoster constantly is applied in the affected part with the compositions water preparation.

6.3.4.2, the result: see Table 16.

The mucilage of table 16. clinical administration 0.5g/25ml is treated the example of 11 routine herpes simplexes and herpes zoster

Name	Sex	Age	Time	Clinical symptoms	The result
						Yellow * * gold * Soviet Union * * bundle * Jiang * * Ke * * Lin * peace * * party * ten thousand * * single * *	Men and women men and women man men and women man men and women man	55 61 48 37 45 29 18 35 71 69 22	03.5.26 03.9.18 03.10.14 98.11.9 99.1.6 99.3.14 99.5.5 99.9.9 99.12.24 00.2.25 00.9.27	Lower limb top, left side herpes zoster, the big right back of lymph node herpes zoster, pain, the left lower limb top herpes zoster that generates heat, the big right zoster frontalis of lymph node, the lymphadenectasis bicker is blistered, red, the right shoulder herpes zoster of pain, the big bicker of lymph node is blistered, red, pain back herpes zoster, red, pain waist herpes zoster, pain, heating forehead to hairline has herpes zoster, pain right leg herpes zoster, lymph node is big	The bleb incrustation bleb incrustation bleb incrustation bleb incrustation bleb incrustation bleb incrustation bleb incrustation bleb incrustation bleb incrustation bleb incrustation bleb incrustation that disappeared in 3 days that disappeared in 3 days that disappeared in 2.5 days that disappeared in 2 days that disappeared in 1.5 days that disappeared in 2.5 days that disappeared in 2 days that disappeared in 2.5 days that disappeared in 2.5 days that disappeared in 3 days 2.5 it disappears

6.3.4.2, conclusion: from the patient of visible clinical use combination treatment herpes simplex of table 16. and herpes zoster, thus its dosage between 0.2g～0.5g, and can pain relieving in 1 to 3 day, the bleb that disappears, incrustation reach recovery from illness, reaches the curative effect of feeling quite pleased.Wherein drug concentrations and herpes area size has substantial connection with curative effect.

6.3.5, the result of implementation of compositions clinical treatment infantile parotitis:

6.3.5.1, method: get compositions and make every tablet of " buccal tablet " that contains compositions 50mg, per hour containing is 1, administration every day 3 times, two days administration 0.3g altogether.

6.3.5.2, the result of implementation of clinical treatment infantile parotitis sees Table 17.:

The clinical example for the treatment of 12 routine parotitis children for buccal tablet 50mg/ sheet of table 17.

Name	Sex	Age	Time	Clinical symptoms	The result
						Zheng * separate * Tong * *	Woman man man	8 7 10	03.4.14 03.5.9 03.9.22	The red and swollen fever of the rubescent pain of right side parotid gland enlargement right side parotid gland enlargement fever pain bilateral parotid gland pain	Detumescence next day, detumescence next day of bringing down a fever, the recovery from illness of bringing down a fever of subsiding a swelling in 1.5 days of fully recovering in two days

Beam * witch * * huge * * Mulberry * Ke * * insult * * wingceltis * * Miao * *

Women men and women woman man man man

9 11 6 13 10 10 5 8

04.3.9 04.4.6 04.428 04.10.21 04.11.13 05.4.19 05.04.19 05.11.06

The rubescent pain of the red and swollen fever of the left side parotid gland pain right side parotid gland red and swollen fever pain bilateral parotid gland enlargement rubescent pain bilateral parotid gland red and swollen fever pain bilateral parotid gland enlargement rubescent pain right side parotid gland red and swollen fever pain left side parotid gland enlargement rubescent pain bilateral parotid gland enlargement

Subside a swelling that subsiding a swelling 1.5 days next day of fully recovering fully recovered in 2 days next day and subsided a swelling in 1.5 days subsiding a swelling two days next day of fully recovering fully recovered in 1.5 days detumescence next day of subsiding a swelling that fully recovering in 1.5 days brought down a fever in 1 day in 1 day and fully recovered in 1.5 days, and recovery from illness detumescence next day, and recovery from illness

6.3.5.3, conclusion: the result of implementation of compositions clinical treatment infantile parotitis as can be seen behind buccal tablet 50mg * 3 slice/day of the clinical use compositions of parotitis sick child, only needs can fully recover in about 2 days, can obtain the curative effect of specific drug.

6.3.6, the actual efficacy of the viral sexually transmitted disease condyloma of compositions clinical treatment:

6.3.6.1, method: during the viral sexually transmitted disease condyloma of compositions clinical treatment, adopt method oral and that external combines, the promptly clinical 0.25g/cm that gives ²Membrane and give oral treatment of tablet that content is 0.1g, obtain better effect.

6.3.6.2, curative effect: see Table 18.:

The clinical example that gives membrane and tablet in treatment 7 routine condyloma acuminatum patients of table 18.

Name	Sex	Age	Time	Disease and usage	The result
						Recklessly * * Tang * * side * * osmanthus * indigo plant * * Dong * * Europe * *	Men and women men and women man	41 26 48 39 29 23 28	03.04.22 03.08.17 04.10.15 04.12.07 05.02.26 05.05.09 05.10.17	Be the external genitalia condyloma acuminatum all through hospital diagnosis.Its medication film got wet and was attached to the affected part after moistening treatment season, changed dressings every day once and was aided with that tablet is oral adheres to taking a turn for the better or recovery from illness.	Cure healing in 23 days healing in 21 days in 20 days and cured the improvement in 19 days that took a turn for the better in 18 days that took a turn for the better in 15 days in 27 days

6.3.6.3, conclusion: the compositions clinical practice is treated viral sexually transmitted disease (STD) " condyloma acuminatum " and is obtained the effect of making us more satisfied equally.

6.3.7, compositions uses the example of flu-prevention, parotitis etc. as " disinfectant ".

6.3.7.1, method: " disinfectant " of using compositions as: aerosol spray is sprayed in the oral cavity, nasal drop collunarium, oral chewing gum or liquid chewing gum etc. in nasal cavity.

6.3.7.2, the result: compositions " disinfectant " flu-prevention and parotitis effect see Table 19.:

The example of table 19. compositions " disinfectant " flu-prevention, parotitis etc.

Name	Sex	Age	Time	Living environment	Use the result
						Occupy * * Wu * * once * * Hao * Mulberry * side * Gu * * Lustful * * Pang * Cai * * Chu * * Tong * health * *	Woman men and women woman men and women men and women woman men and women	27 10 11 8 21 47 9 55 63 14 29 7 19	03.1.13 03.1.22 03.2.15 03.11.09 03.12.24 04.01.17 04.04.06 04.02.21 04.02.27 04.11.23 04.12.26 05.01.12 05.02.07	The number people suffer from the influenza pandemic sister in law of influenza pandemic unit of the popular office of parotitis of the popular school of parotitis of the popular school of parotitis of influenza school and all suffer from the parotitis man number people and suffer from that the number people suffer from influenza influenza pandemic between the popular colleague of influenza pandemic kindergarten parotitis between classmate's influenza pandemic friend in the class in the influenza man in the family	With behind the collunarium disinfectant morbidity with do not infect after the liquid chewing gum with behind the aerial fog disinfectant morbidity with do not fall ill behind the collunarium disinfectant with infect after the chewing gum with do not fall ill behind the collunarium disinfectant with do not fall ill behind the aerial fog disinfectant with do not fall ill behind the aerial fog disinfectant with behind the aerial fog disinfectant morbidity with do not fall ill behind the collunarium disinfectant with behind the aerial fog disinfectant morbidity use to fall ill behind the collunarium disinfectant and use infection after the liquid chewing gum

6.3.7.3, conclusion: " disinfectant " that the aerosol made from compositions, nasal drop, chewing gum, liquid chewing gum etc. are applied as the prevention Respirovirus obtains the effect of making us more satisfied.

Claims (14)

1. broad-spectrum antiviral medicament, it is characterized in that sulfated polysaccharide ester or sulfonic acid polysaccharide ester and its esters from a kind of Stellaria plant extract, with phenols especially with the total flavones that comprises apigenin with the carbon glycosidic bond or/and the molecular weight distribution that the oxygen glycosidic bond forms 50, below 000, but be mainly molecular weight distribution 4, the total phenolic glycoside composition of a class below 000 is with the total flavones that comprises apigenin and do not contain the pale brown colour cell compound that the glucosides class composition of element sulphur forms and use as broad-spectrum antiviral medicament.

Wherein the total phenols glycoside composition of the total phenols glycoside composition of Herba stellariae mediae sulfated polysaccharide ester or Herba stellariae mediae sulfonic acid polysaccharide ester and the total flavones that comprises apigenin and the ratio that do not contain the glucosides class composition of element sulphur thereof are 9.0～9.8 to 1.0～0.2.

2. the described total phenols glycoside of claim 1 composition is by saturated or/and undersaturated sulfated polysaccharide ester or sulfonic acid polysaccharide ester and its esters and phenols, especially with the total flavones that comprises apigenin with the carbon glycosidic bond or/and the total phenols glycoside composition that the oxygen glycosidic bond forms.

3. claim 1 described " a kind of Stellaria plant " comprises following 79 kinds: Herba stellariae mediae, Stellaria alsine Grim., brown lobe Stellaria alsine Grim., the Anhui Herba stellariae mediae, blunt calyx Herba stellariae mediae, the apicule Herba stellariae mediae, Herba malachii aquatici, the husky Herba stellariae mediae of giving birth to, the Alishan Herba stellariae mediae, slender lobule Alishan Herba stellariae mediae, the north Herba stellariae mediae, short lobe Herba stellariae mediae, long lobe Herba stellariae mediae, the northeast Herba stellariae mediae, China's Herba stellariae mediae, the Taiwan Herba stellariae mediae, thick leaf Herba stellariae mediae, wrinkle leaf Herba stellariae mediae, David's Herba stellariae mediae, the Herba stellariae mediae for sleeping in of laying down, the needle-like Herba stellariae mediae for sleeping in of laying down, the southwest Herba stellariae mediae, Stellaria dianthifolia Williams, the forked cyme Herba stellariae mediae, the bifid Herba stellariae mediae, narrow leaf bifid Herba stellariae mediae, line leaf bifid Herba stellariae mediae, Herba stellariae mediae looses in the shop, turn over white Herba stellariae mediae, Stellaria diversiflora Maxim., the different colored Herba stellariae mediae of naked stamen, the concave veins Herba stellariae mediae, the Du Shi Herba stellariae mediae, line stem Herba stellariae mediae, line handle Herba stellariae mediae, spend more Herba stellariae mediae, standing grain leaf Herba stellariae mediae, dredge pubescence standing grain leaf Herba stellariae mediae, turn green standing grain leaf Herba stellariae mediae, Jiangzi's Herba stellariae mediae, the XIACAO Herba stellariae mediae, Stellaria henryi williams, Xingan's Herba stellariae mediae, the introversion Herba stellariae mediae, the slender lobule Herba stellariae mediae, Stellaria maximowixziana Franch., Stellaria micrantha Hayata, gentle Herba stellariae mediae, goose intestinal Herba stellariae mediae, Herba stellariae mediae is given birth in new natural pond, eight stamen Herba stellariae mediaes, the raspberry Herba stellariae mediae, Herba stellariae mediae is given birth in the natural pond, exhibition leaf Herba stellariae mediae, handle flower Herba stellariae mediae, handle leaf Herba stellariae mediae, Herba stellariae mediae becomes mildewed, imitation stone is given birth to Herba stellariae mediae, blinks, flint lobe Herba stellariae mediae, net arteries and veins Herba stellariae mediae, the rock Herba stellariae mediae, stone is given birth to Herba stellariae mediae, embrace stem stone and give birth to Herba stellariae mediae, accurate Ge Er Herba stellariae mediae, the Su Shi Herba stellariae mediae, star hair Herba stellariae mediae, garden calyx Herba stellariae mediae, intend umbrella flower Herba stellariae mediae, little fine hair Herba stellariae mediae, three type Herba stellariae mediaes, the Turkestan Herba stellariae mediae, the wetland Herba stellariae mediae, umbrella flower Herba stellariae mediae, the LVHUA Herba stellariae mediae, Stellaria wushanensis Williams, five Herba stellariae mediaes, Yunnan Herba stellariae mediae or cattle Stellaria plant cattle Herba stellariae mediae.

4. the described preparation of compositions method 1 of claim 1, its step comprises: bright grass or the fresh and dried grass of plant Herba stellariae mediae or other a kind of Stellaria plant are cleaned silt, are pulverized the back and extract aqueous solution, with this aqueous solution through precipitation, centrifugal or filter after obtain liquid A; With liquid A by the macroporous resin column handled well in advance to adsorb the composition of described compositions, wash post with water, with macroporous resin column heat the back with thermal distillation washing post to clean impurity, collect effusive dark brown distilled water liquid, reuse is heated back concentration at the eluting from the resin column of the lower alcohol below 59%, and collect brownish red or the dark brown-red solution that eluting obtains, to merge with the dark brown water liquid of collecting behind this brownish red or the dark brown-red solution recovery ethanol, be concentrated into than weigh about 0.8 leave standstill after centrifugal again removal precipitate, continue to be concentrated into proportion 1.00 to 1.20 and afterwards pass through spray drying or vacuum drying promptly, compositions character and character are: the pale brown toner powder that a kind of tool Chinese medicine dry extract is common, common Chinese medicine dry extract abnormal smells from the patient is arranged, its stable in properties, soluble in water, bitterness slightly;

Wherein column temperature is 40 ℃～59 ℃, and lower alcohol comprises methanol, ethanol, propanol, n-butyl alcohol, the isobutanol below 59%; Preferred 50 ℃～55 ℃ column temperature and 50%～55% ethanol of uniform temp.

5. the described preparation of compositions method 2 of claim 1, its step comprises: the back is cleaned, pulverized to bright grass or the bright Radix Glycyrrhizae of plant Herba stellariae mediae or other a kind of Stellaria plant extract aqueous solution, with this aqueous solution through precipitation, centrifugal or filter after obtain liquid A; With this liquid A through the anionite post, described compositions composition is adsorbed on the post, with sodium chloride solution the post of described compositions composition after heat eluted, again through desalting processing, leave standstill after being concentrated into proportion about 0.8, centrifugal removal precipitate, continue again to be concentrated into than weighing the spray-dried or vacuum drying in 1.00 to 1.20 backs promptly, compositions character and character are: a kind of have the common pale brown toner of a Chinese medicine dry extract end, common Chinese medicine dry extract abnormal smells from the patient is arranged, its stable in properties, soluble in water, slightly bitterness;

Wherein the anionite post comprises weak anion exchange resin post and cellulose anion exchanger post; Column temperature is 40 ℃～59 ℃, preferred 50 ℃～55 ℃.

6. the described preparation of compositions method 3 of claim 1, its step comprises: bright grass or the bright Radix Glycyrrhizae of plant Herba stellariae mediae or other a kind of Stellaria plant are cleaned, pulverize the back and extract aqueous solution, with this aqueous solution through the precipitation, centrifugal or filter after be evaporated to proportion about about 0.8, add lower alcohol and make concentration of lower alcohols reach 75%, a large amount of muddinesses promptly appear in solution, leave standstill about 12 hours, the sucking-off supernatant, precipitate through centrifugal or filter the compositions crude product, this crude product reuse pure water dissolving back is added lower alcohol to be made and reaches 85% concentration and carry out the secondary precipitate with ethanol, leave standstill the sucking-off supernatant about 12 hours, precipitate is added an amount of dehydrated alcohol and washing with acetone through decompress filter and timely priority, sucking filtration is extremely done, and promptly gets powdered composition through the proper temperature vacuum drying immediately.

7. the application of the described compositions of claim 1 in preparation treatment HIV (human immunodeficiency virus) (Human Immunodeficiency Virus) medicine.

8. the described compositions of claim 1 comprises the application in the medicine for the treatment of bird flu virus preparation treatment influenza virus.

9. the application of the described compositions of claim 1 in preparation treatment hepatitis virus medicament.

10. the application of the described compositions of claim 1 in preparation treatment herpesvirus medicament.

11. the application of the described compositions of claim 1 in preparation treatment mumps virus medicine.

12. the application of the described compositions of claim 1 in preparation treatment condyloma acuminatum medicine.

13. the application of the described compositions of claim 1 in the antiviral disinfectant of preparation.

14. the application of the described compositions of claim 1 in the antiviral health product of preparation.