Chinese medicine Herba Cirsii and method for making, pharmaceutical composition and purposes
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of Chinese medicine Herba Cirsii and preparation method thereof, comprise pharmaceutical composition and the purposes of this Herba Cirsii.
Background technology
Varicosis has become the common disease of harm people's life health, weight, lack exercise, oral contraceptive, pregnancy, climacteric, obesity, aging, the factor such as heredity all can cause varicosis.Varicosis can cause the generation of hemorrhoid, and hemorrhoid are that be a kind of common disease, its sickness rate is about 25-40%, and the sickness rate of more than 50 years old old people is 60-70% due under the mucosa of rectum lower end and anal canal or the subcutaneous varicosis of anus edge, expand and cause.When patient suffers from hemorrhoid, there will be have blood in stool, the symptom such as hemorrhoid block comes off, pain, pruritus, bring very large inconvenience and misery to the life of patient.Varicose veins of the lower extremity is also varicose vein disease the most common, and prevalence is up to about 5-30%.Main clinical manifestation comprises lower limb Superficial veins and expands, extends, bends to bulk; Patient has that leg is heavy, weak, swollen, the twinge of acid, feeling of numbness, edema, scratchiness, exacerbation of symptoms after standing for a long time or walking; End-stage disease can occur that the scleroma of Superficial veins thrombosis is formed, venous ulcer (being commonly called as " always rotten lower limb ").There is affected part angiorrhexis acute hemorrhage in some patients, or chronic skin ulcer is prolonged does not heal, amputation and even threat to life.
It is cause cirsoid main cause that vein tube wall strength reduction and intravenous pressure raise, and therefore, increases the tension force of vein blood vessel, reduces intravenous pressure and just effectively can treat varicosis.
Herba Cirsii is the dry aerial parts of feverfew perverse youngster's dish Cirsium setosum (Willd.) MB..Its sweet in the mouth, hardship, cool in nature; GUIXIN, Liver Channel.There is cooling blood for hemostasis, effect of removing blood stasis to reduce swelling.Its preparation blood stops immediately sheet, blood stops immediately capsule and blood stops immediately granule all for epistaxis, and spit blood, hematuria, has blood in stool, metrostaxis, the treatment of traumatic hemorrhage etc.But have no the related application and the research report that are used for the treatment of varicose disease about Herba Cirsii.
Summary of the invention
An object of the present invention is to provide a kind of Herba Cirsii with good varicosis activity and treatment hemorrhage.
Another object of the present invention is the preparation method providing a kind of above-mentioned Herba Cirsii.
Another object of the present invention is to provide a kind of pharmaceutical composition comprising above-mentioned Herba Cirsii.
Another object of the present invention is to provide the purposes of above-mentioned Herba Cirsii.
The present invention, on the basis studied Herba Cirsii chemical composition and pharmacologically active, finds that the flavones ingredient comprised in this plant has the edema significantly suppressing local inflammation to cause, the effect reducing faint pulse vascular permeability.
The object of the invention is to be achieved through the following technical solutions:
On the one hand, the invention provides a kind of Herba Cirsii, described Herba Cirsii comprises the flavone compound as sole active agent.
Preferably, described flavone compound mainly comprises linarin, rutin, acacetin and Quercetin etc.
Preferably, in described Herba Cirsii, the content of Flavonoids is greater than 50%(weight).
On the other hand, the invention provides a kind of method preparing above-mentioned Herba Cirsii, said method comprising the steps of:
(1) Herba Cirsii medical material is got through solvent extraction;
(2) extracting solution of step (1) gained is evaporated to proper volume, puts to room temperature, centrifugal, obtain precipitation;
(3) by the precipitation in step (2) with after organic solvent extraction defat, discard organic layer, precipitation drying after namely obtain Herba Cirsii; Or the precipitation aqueous slkali in step (2) is dissolved, filters, after filtrate being purified with macroporous adsorptive resins, obtain Herba Cirsii.
Preferably, the extracting method in described step (1) is warm macerating, hot reflux and/or percolation; Preferably, the solvent in described step (1) be selected from water, aqueous slkali, methanol, ethanol and acetone one or more, wherein, when extracting with aqueous slkali, step also comprises the step first with aqueous acid, solution ph being adjusted to 3-7 in (2); Preferred described aqueous slkali is lime water, sodium hydrate aqueous solution, potassium hydroxide aqueous solution or aqueous sodium carbonate etc.; Preferably, described acid is hydrochloric acid or sulphuric acid etc.
Preferably, the organic solvent in described step (3) is petroleum ether, ether, dichloromethane, chloroform or ethyl acetate etc.; Preferably, the aqueous slkali in described step (3) is lime water, sodium hydrate aqueous solution, potassium hydroxide aqueous solution or aqueous sodium carbonate etc.; Preferably, the macroporous adsorptive resins in described step (3) is nonpolarity macroporous adsorptive resins chromatographic column, as HPD-300 macroporous adsorptive resins etc.
Preferably, described step (3) comprises the precipitation aqueous slkali after by defat further and dissolves, and filters, adds aqueous acid adjust ph to 3-7 in filtrate, and by the sedimentation and filtration of separating out, washing, namely obtains Herba Cirsii after drying; Preferably, described aqueous slkali is lime water, sodium hydrate aqueous solution, potassium hydroxide aqueous solution or aqueous sodium carbonate etc., and preferably, described acid is hydrochloric acid or sulphuric acid etc.
Above-mentioned preparation method is simple, extraction effect good, be easy to commercial introduction application.
Another aspect, the invention provides a kind of pharmaceutical composition, and described pharmaceutical composition comprises above-mentioned Herba Cirsii.
Preferably, described pharmaceutical composition is capsule, tablet, granule, drop pill, soft capsule, dispersible tablet, oral cavity disintegration tablet, slow releasing tablet, controlled release tablet, injection, transfusion or injectable sterile powder.
Conventional method can be adopted Herba Cirsii and any one or more than one pharmaceutic adjuvants, as starch, dextrin, lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, carboxymethyl starch sodium, Polyethylene Glycol, magnesium stearate, micropowder silica gel, glucose, mannitol, xylitol, glycine etc. are mixed and made into above-mentioned dosage form.
Again on the one hand, the invention provides described Herba Cirsii and prepare the purposes prevented and/or treated in the medicine of varicose vein disease.
Preferably, wherein said varicose vein disease is hemorrhoid or varicose veins of the lower extremity etc.
In Herba Cirsii, the content assaying method of total flavones is as follows:
The mensuration (spectrophotography) of total flavones
The preparation of reference substance solution: the linarin reference substance that precision takes dry constant weight is appropriate, makes the solution of every 1ml containing 15 μ g with dissolve with methanol, to obtain final product.
The preparation of need testing solution: precision takes this product powder 50mg, and put in 10ml measuring bottle, adding distil water is dissolved to scale, shakes up, filters.Precipitation connects filter paper and is placed in 100ml tool plug conical flask, and add methanol 50ml, accurately weighed weight, supersound process 30min, weighs again, adds the weight that methanol supplies less loss, shakes up, and filters.Get subsequent filtrate 1ml, put in 25ml measuring bottle, add methanol to scale, shake up, to obtain final product.
The drafting of standard curve: precision measure linarin reference substance solution (0.13mg/ml) 1.0,2.0,3.0,4.0,5.0,6.0ml, putting respectively in 25ml measuring bottle, add methanol to scale, shake up, take methanol as blank, measures absorbance at 326mn wavelength place.With trap (A) for vertical coordinate, concentration C (μ gml
-1) be abscissa, drawing standard curve.
Algoscopy: get need testing solution take methanol as blank, according to spectrophotography (China's coastal port annex VA), measures trap at 326nm wavelength place.
Preliminary study is carried out to the pharmacodynamics part of medicine of the present invention, found that medicine Dichlorodiphenyl Acetate of the present invention causes rat Perianal ulceration and has obvious therapeutic action.On the basis of above-mentioned pharmacological activity test, Herba Cirsii can be used for the prevention and treatment of diseases such as hemorrhoid, varicose veins of the lower extremity clinical.
Medicine material source of the present invention is easy to get, be easy to industrialization, various dosage form can be made as required, for clinical providing uses convenient, that treatment is more effective, quality is more controlled modern Chinese medicine, for patient brings more benefit, thus create huge social benefit.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is further described in detail, the embodiment provided only in order to illustrate the present invention, instead of in order to limit the scope of the invention.
embodiment 1
Get Herba Cirsii medical material 10kg, with 100L 80%(volume) ethanol extraction three times, each 1 hour.Collect extracting solution, decompression recycling ethanol, and be concentrated into 10L, be placed to room temperature, centrifugal, precipitate through defat with petroleum ether, be drying to obtain Herba Cirsii.By the total weight of Herba Cirsii, general flavone content is 68.9%(weight).
embodiment 2
Get Herba Cirsii medical material 10kg, with 250L 70%(volume) ethanol percolate extraction, collect percolate, decompression recycling ethanol, and be concentrated into 10L, be placed to room temperature.Centrifugal, precipitate through chloroform defat, obtain Herba Cirsii.By the total weight of Herba Cirsii, general flavone content is 65.7%(weight).
embodiment 3
Get Herba Cirsii medical material 10kg, with 100L 80%(volume) ethanol extraction three times, each 2 hours, collect extracting solution, decompression recycling ethanol, and be concentrated into 10L, be placed to room temperature.Centrifugal, precipitate through methanol supersound process, sucking filtration, discards methanol solution, and precipitation is dry, obtains Herba Cirsii.By the total weight of Herba Cirsii, general flavone content is 70.1%(weight).
embodiment 4
Get Herba Cirsii medical material 10kg, with the limewater extraction 2 times of 100L pH8-9, each 1 hour, filter, collect filtrate, salt adding acid for adjusting pH to 3-4, and is concentrated into 10L, hold over night.Centrifugal, precipitate through chloroform heat treated, sucking filtration, discards chloroform solution, and precipitation is dry, obtains Herba Cirsii.By the total weight of Herba Cirsii, general flavone content is 52.1%(weight).
embodiment 5
Get Herba Cirsii medical material 10kg, with 100L 70%(volume) ethanol extraction three times, each 2 hours, collect extracting solution, decompression recycling ethanol, and be concentrated into 10L, be placed to room temperature.Centrifugal, precipitate through the process of dichloromethane merceration, sucking filtration, discard dichloromethane solution, precipitation 20L concentration 2%(weight/volume) sodium hydrate aqueous solution dissolving, filter, in filtrate, add 20L medicinal alcohol, pH to 5 is regulated with concentrated hydrochloric acid, hold over night, separates out precipitation, sucking filtration, precipitation clear water fully cleans to pH neutral, obtains Herba Cirsii.By the total weight of Herba Cirsii, general flavone content is 72.9%(weight).
embodiment 6
Get Herba Cirsii medical material 10kg, with 100L 80%(volume) ethanol extraction secondary, each 2 hours, collect extracting solution, decompression recycling ethanol, and be concentrated into 10L, be placed to room temperature.Centrifugal, precipitation 20L concentration 2%(weight/volume) sodium hydrate aqueous solution dissolving, filter, get filtrate, by HPD-300 macroporous adsorptive resins, it is neutral for being first washed till effluent pH value with distilled water, use 70%(volume again) concentration ethanol eluting 20L, collect 70%(volume) alcoholic solution, decompression recycling ethanol is also concentrated into dry, obtains Herba Cirsii.By the total weight of Herba Cirsii, general flavone content is 85.3%(weight).
embodiment 7
Get Herba Cirsii 100g, micropowder silica gel is appropriate, mix homogeneously, adopts capsules preparation technique preparation, obtains Herba Cirsii capsule.
embodiment 8
Get Herba Cirsii 100g, be added in the polyethylene glycol 6000 of 200g melting, adopt drop pill preparation technology preparation, obtain Herba Cirsii drop pill.
embodiment 9
Get Herba Cirsii 100g, dextrin 200g, mix homogeneously, granulate, sieve, dry, obtain the granule of Herba Cirsii; Maybe by obtained granule through further tabletting, dry, obtain the tablet of Herba Cirsii.
embodiment 10
Get Herba Cirsii 100g, hydroxypropyl emthylcellulose 100g, sodium carboxymethyl cellulose 60g, lactose 40g, mix homogeneously, granulate, dry, tabletting, obtains the slow releasing tablet of Herba Cirsii.
embodiment 11
Get Herba Cirsii 100g, microcrystalline Cellulose 120g, sodium carboxymethyl cellulose 30g, micropowder silica gel 1g, mix homogeneously, tabletting, obtain the dispersible tablet of Herba Cirsii.
embodiment 12
Get Herba Cirsii 100g, vegetable oil 250g, mixing, makes capsule casing material with gelatin, is pressed into soft capsule, obtain the soft capsule of Herba Cirsii.
embodiment 13
Get Herba Cirsii 10g, be dissolved in 500ml water for injection, adopt existing injectable sterile powder preparation technology to prepare, obtain Herba Cirsii injectable sterile powder dosage form.
embodiment 14
Get Herba Cirsii 10g, be dissolved in 1000ml water for injection, adopt process for preparation of injection, obtain Herba Cirsii injection (containing transfusion).
test example 1
The curative effect of medicine of the present invention is proved by following pharmacodynamics test:
1, test material
1.1 medicines and reagent
Herba Cirsii: sample prepared by embodiment 1, brown ceramic powder (general flavone content is greater than 50%(weight)).The solution being made into suitable concn with normal saline is for experiment.
Alvenor (diosmin sheet): purchased from Shi Weiya (Tianjin) pharmaceutical Co. Ltd.
1.2 animal
Rat: SD rat, male and female dual-purpose, body weight 160-180g, purchased from Hua Bukang biotech inc, Beijing.
2, Dichlorodiphenyl Acetate causes the impact of rat Perianal ulceration
Get SD rat 50, male and female half and half, body weight 160-180g.Perianal ulcer is caused: be that the filter paper of 8mm launches and put into glacial acetic acid fully to soak by equal and opposite in direction internal diameter with acetic acid, then all rats filter paper being soaked with glacial acetic acid is sticked anus, filter paper need be close to anal skin and mucosa, and 0.5min, 1min change filter paper.Within 2nd day, divide 4 groups at random by rat, gastric infusion by body weight and ulcer level.Model control group is to equal-volume distilled water; Herba Cirsii 200,400mg/kg group; Positive controls.In administration the 3rd, 5,7,9 days according to rat ulcer healing state, evaluation ulcer level.Evaluation criteria: have ulcer sepage 1 point; A little ulcer sepage 2 points; Eschar is had substantially to heal 3 points; Heal 4 points completely.White ulcer surface, crissum swelling have inflammatory seep is all there is in each treated animal after sticking the glacial acetic acid filter paper of 99%.
Table 1 Herba Cirsii Dichlorodiphenyl Acetate cause rat Perianal ulceration impact (
, n=10)
Table 1 result shows, Herba Cirsii 200 and 400mg/kg dosage treated animal self administration of medication play Perianal ulceration on the 5th day and namely take an evident turn for the better, substantially, healed by the 9th day, ulcer level scoring is compared with model control group significant difference (P<0.05 or P<0.01).
Therefore, Chinese medicine Herba Cirsii of the present invention has good therapeutic effect to Perianal ulceration, suppresses the edema that local inflammation causes significantly.