CN101933966A - Active site composition of isatis roots, as well as preparation method and application thereof - Google Patents
Active site composition of isatis roots, as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN101933966A CN101933966A CN 201010269954 CN201010269954A CN101933966A CN 101933966 A CN101933966 A CN 101933966A CN 201010269954 CN201010269954 CN 201010269954 CN 201010269954 A CN201010269954 A CN 201010269954A CN 101933966 A CN101933966 A CN 101933966A
- Authority
- CN
- China
- Prior art keywords
- radix isatidis
- total
- active site
- compositions
- parts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
The invention discloses an active site composition of isatis roots, as well as a preparation method and the application thereof. The active site composition of isatis roots is prepared from a general phenylpropanoid part of isatis roots, a total alkaloid part, a total organic acid part and a total polysaccharide part. The active site composition obtained by the invention has high effective component contents and accurate active components. Proved by experimental results, the active site composition of isatis roots has obvious antiviral activity and favorable antibacterial and antipyretic activities. After being combined, the effective components reach favorable synergy, exert the antiviral, antibacterial and antipyretic activities at a plurality of targets spots through multiple paths, can be used for treating a viral disease with the bacterial inflammation of a febrile disease and have a wider clinical application range. Moreover, the invention optimizes and designs the extracting and refining process according to the physicochemical properties of the effective components, the active parts obtained through preparation has high effective component contents, and the preparation method has strong maneuverability and can realize industrialized mass production.
Description
Technical field
The present invention relates to a kind of Radix Isatidis pharmaceutical preparation, be specifically related to a kind of have antiviral activity, the thermoactive Radix Isatidis active site of antibiotic reconciliation composition and method of making the same, belong to medical technical field.
Background technology
Radix Isatidis has heat-clearing and toxic substances removing, removing heat from blood sore-throat relieving function, be usually used in viral disease and bacterial infective diseases clinically in the modern times, especially at the anti-virus aspect determined curative effect, multiple diseases such as the influenza that numerous bibliographical information Radix Isatidis cause for virus, hepatitis B, herpes simplex, viral myocarditis, hemorrahgic fever with renal syndrome all have treatment or preventive effect preferably clinically.As one of heat-clearing and toxic substances removing conventional Chinese medicine, Radix Isatidis is presented as antiviral, improves immunity and antioxidative synergism on modern pharmacology, thereby shows heat-clearing toxin-expelling functions through too many levels, multipath performance synergism in vivo by plurality of active ingredients.
The external in recent years concern to the Isatis indigotica Fort. platymiscium is that on the anti-tumor activity of indoles alkaloid, the research of antiviral ingredients does not then appear in the newspapers.Domestic research to Radix Isatidis focuses mostly in applications such as clinical and preparation process, and the basic research work of material base, active component is then relatively weaker.People such as Liu Yunhai once did the screening of Radix Isatidis antiendotoxin active component, but the maximum clinically advantage of Radix Isatidis is the treatment and the prevention of virus, and the separation of antiviral ingredients and the research of screening active ingredients seldom and do not have system.Comprehensive existing achievement in research shows that the composition relevant with the Radix Isatidis antivirus action mainly concentrates on the high polarity position, and this and Radix Isatidis clinical practice are the principal phase symbol with the water extract.Japan scholar Yamada thinks that the Radix Isatidis antiviral ingredients is glycoprotein and polysaccharide, and isolate the antiviral polysaccharide of unimodal molecular weight, in his result of study, also show, the Radix Isatidis polysaccharide is except that having direct antivirus action, also can promote the generation of resisiting influenza virus IgG antibody, can be used as the adjuvant of antiviral vaccine.Chinese scholar discovers that also the antiviral ingredients of Radix Isatidis is the agglutinin composition in its water extract, also has experimental result to confirm that effective site is in conjunction with aminoacid.4 (3H)-quinazolones in the Radix Isatidis alkaloid component have the activity that suppresses influenza virus, Coxsackie virus through the pharmacological evaluation proof, also can significantly promote splenocyte propagation and the inductive lymphopoiesis of canavaline.In addition, the Radix Isatidis antivirus action also may be closely related with wherein immunomodulating composition and anti-inflammatory component; Virus usually merges bacterial infection, so the antibiotic and antiendotoxin composition in the Radix Isatidis also may be brought into play certain effect in antiviral therapy.At present, existing people quite a lot studies the position of Radix Isatidis, comprises alkaloid, organic acid etc., but the content of effective site is not very high, method for extraction and purification is also inconsistent, does not particularly have to carry out the report that drug effect is used after the active site combination.
Summary of the invention
Goal of the invention: the objective of the invention is in order to overcome the deficiencies in the prior art, a kind of have strong antiviral and antibiotic, analgesic multiple activity are provided, and the Radix Isatidis active site compositions that active constituent content is high, another object of the present invention provide Radix Isatidis active site preparation of compositions method and its application.
Technical scheme: in order to realize above purpose, the technical scheme that the present invention takes is:
Radix Isatidis active site compositions, it is made up of following raw materials according: Radix Isatidis total phenylpropanoid position and Radix Isatidis total organic acids position.
As preferred version, Radix Isatidis active site compositions, it is made up of the raw material of following parts by weight: 10～90 parts at Radix Isatidis total phenylpropanoid position, 10～90 parts at Radix Isatidis total organic acids position.As more preferably scheme, it is made up of the raw material of following parts by weight: 30 parts at Radix Isatidis total phenylpropanoid position, 40 parts at Radix Isatidis total organic acids position.
As another preferred version, Radix Isatidis active site compositions, it is made up of the raw material of following parts by weight:
10～90 parts at Radix Isatidis total phenylpropanoid position, 10～90 parts at Radix Isatidis total organic acids position, 10～90 parts at Radix Isatidis total alkaloids position.As more preferably scheme, it is made up of the raw material of following parts by weight: 30 parts at Radix Isatidis total phenylpropanoid position, 40 parts at Radix Isatidis total organic acids position, 20 parts at Radix Isatidis total alkaloids position.
As another preferred version, Radix Isatidis active site compositions, it is made up of the raw material of following parts by weight:
10～90 parts of Radix Isatidis total phenylpropanoids, 10～90 parts of Radix Isatidis total organic acidss, 10～90 parts of Radix Isatidis total polysaccharidess, 10～90 parts of Radix Isatidis total alkaloidss.
As further preferred version, Radix Isatidis active site compositions, it is made up of the raw material of following parts by weight:
30 parts of Radix Isatidis total phenylpropanoids, 20 parts of total alkaloidss, 40 parts of total organic acidss, 40 parts of total polysaccharidess.
As preferred version, above-described Radix Isatidis active site compositions, described Radix Isatidis total phenylpropanoid position is the Radix Isatidis extract that contains weight percentage 50%～100% total phenylpropanoid; The total alkaloids position is the Radix Isatidis extract that contains weight percentage 50%～100% total alkaloids; The total organic acids position is the extract that contains weight percentage 50%～100% total organic acids, and the total polysaccharides position is the extract that contains weight percentage 50%～100% total polysaccharides.
Radix Isatidis active site compositions of the present invention, wherein the Radix Isatidis total phenylpropanoid includes different larch lipidol, different larch lipidol-4-O-β-D-glucoside, lariciresinol-4-O-β-D-glucoside, lariciresinol-4,4 '-two-O-β-D-diglucoside, compositions such as ligustrin, total alkaloids includes indole-3-acetonitrile-6-O-β-D-glucoside, 3-[2 '-(5 '-methylol) furyl]-1 (2H)-isoquinolines-7-O-β-D-glucoside], couroupitine A, according to indigo ketone, according to compositions such as indigo diketones, total organic acids includes salicylic acid, 2-hydroxyl-1, the 4-phthalic acid, 3-indolyl acetic acid, maleic acid, syringic acid, benzoic acid, compositions such as succinic acid.
Above-described Radix Isatidis active site compositions is made Radix Isatidis active site compositions and pharmaceutically acceptable carrier the medicine of capsule, tablet, drop pill, granule, injection, encapsulated form.
Radix Isatidis active site compositions provided by the invention Radix Isatidis active site compositions and carrier lactose or corn starch, adds magnesium stearate lubricant when needing when making tablet, mix homogeneously, and tabletting is made tablet then.When Radix Isatidis active site compositions provided by the invention is made capsule Radix Isatidis active site compositions and carrier lactose or corn starch mix homogeneously, granulate, the encapsulated then capsule of making.When Radix Isatidis active site compositions provided by the invention is made granule, Radix Isatidis active site compositions and diluent lactose or corn starch mix homogeneously, granulate, drying is made granule.
Radix Isatidis active site preparation of compositions method provided by the invention specifically may further comprise the steps:
(1) Radix Isatidis with the Isatis indigotica Fort. platymiscium is a raw material, adopts solvent extraction method, gets extracting solution, and extracting solution adopts ultrafiltration membrance filter, molecular cut off 1000～1000000 parts, the dry Radix Isatidis total polysaccharides position that gets; Or adding alcohol makes determining alcohol reach 30～90% in the extracting solution, place precipitation, filter precipitation and supernatant, precipitate dry Radix Isatidis total polysaccharides position, macroporous adsorbent resin on the supernatant, the first water eluting of getting, reuse concentration 10%～60% alcoholic solution eluting, collect alcohol eluen, concentrate drying gets Radix Isatidis total phenylpropanoid position;
(2) Radix Isatidis with the Isatis indigotica Fort. platymiscium is a raw material, adopts solvent extraction method, gets extracting solution, concentrate, concentrate adds acid extraction, filter acid extraction thing and acid non-soluble substance, the acid extraction thing concentrates the back and goes up cationic exchange resin adsorption, and water and alkaline alcohol solution eluting are collected 10%～90% alkaline alcohol eluting position successively, concentrate, last anion exchange resin, absorption impurity is collected effluent, concentrate drying gets Radix Isatidis total alkaloids position; Anion exchange resin absorption on the acid non-soluble substance, water and acidity alcohol solution eluting are collected 10%～90% acid pure eluting position successively, concentrate, cation exchange resin on the concentrate, absorption impurity is collected effluent, concentrate, drying gets Radix Isatidis total organic acids position;
(3) choose Radix Isatidis total phenylpropanoid position, total organic acids position and/or total alkaloids position and/or total polysaccharides position in proportion, mix homogeneously, promptly.
As preferred version, above-described Radix Isatidis active site preparation of compositions method, solvent extraction method in step (1) and (2) wherein, selecting for use and extracting solvent is that water or concentration are 30%～100% methanol, ethanol, propanol, butanols, amylalcohol, acetone, ethyl acetate or Ethyl formate or their mixed solvent, and extracting method is dipping extraction method, ultrasonic extraction or heating and refluxing extraction method.
As preferred version, macroporous adsorbent resin is oleic series or styrene series resin in the above-described Radix Isatidis active site preparation of compositions method, step (1), as D101 type macroporous resin.
As preferred version, above-described Radix Isatidis active site preparation of compositions method, the separation exquisiteness of total alkaloids can be passed through anion exchange resin earlier in the step (2), obtain by the cation exchange resin eluting again, the separation exquisiteness of total organic acids also can be passed through cation exchange resin earlier, obtains by the anion exchange resin eluting again.
The application of Radix Isatidis active site compositions provided by the invention in preparation antiviral, antibiotic and/or antipyretic analgesics, Radix Isatidis active site compositions provided by the invention also can be used as the heat-clearing and toxic substances removing medicine and uses.
Radix Isatidis active site compositions of the present invention also can become health product with edible preparing carriers, can improve antiviral immunity power.
The present invention shows that by experiment Radix Isatidis active site compositions also can obtain having the compositions of antiviral and antibacterial action by Radix Isatidis total phenylpropanoid and the combination of Radix Isatidis total alkaloids; Perhaps Radix Isatidis active site compositions also can obtain having the compositions of antiviral and antibiotic refrigeration function by Radix Isatidis total organic acids and total alkaloids combination.
Beneficial effect: Radix Isatidis active site compositions provided by the invention is compared with prior art and is had the following advantages:
Radix Isatidis active site compositions provided by the invention, through a large amount of pharmacodynamics screening tests, determine the best of breed of active site, gained active site compositions active constituent content height, active component is clear and definite, show that through experimental result Radix Isatidis active site compositions provided by the invention had both had obvious antiviral activity, have simultaneously antibiotic preferably and antipyretic activity again, after each combination of active principles, reached good synergistic function, many target spots, multipath performance antiviral and antibiotic, antipyretic activity, can be used for the treatment that viral disease merges antibacterial inflammation fever diseases, clinical application range is more extensive.
Radix Isatidis active site preparation of compositions method provided by the invention, physicochemical property optimal design extraction and purification process according to each effective ingredient, the active site active constituent content height for preparing, impurity is few, clinical consumption is few, quality safety, and untoward reaction is low, and preparation method is workable, can realize industrialized great production.
The specific embodiment
According to following embodiment, the present invention may be better understood.Yet, those skilled in the art will readily understand that the described concrete material proportion of embodiment, process conditions and result thereof only are used to illustrate the present invention, and should also can not limit the present invention described in detail in claims.
Embodiment 1 Radix Isatidis active site preparation of compositions
(1) gets Radix Isatidis medical material 1Kg, use 8 times and 6 times of water gaging reflux, extract, 2h, 1.5h respectively, merge extractive liquid,, put coldly, filter, reclaim under reduced pressure concentrates, obtain water and carry the position, in extracting solution, add 95% ethanol, to the ethanol final concentration be 70%, standing over night, filter, filter precipitation and supernatant, precipitate dry Radix Isatidis total polysaccharides position 45g, it is 65.16% that the phenolsulfuric acid method records total polysaccharides content; D101 macroporous adsorbent resin on the supernatant, first water eluting, reuse concentration 10%～60% alcoholic solution eluting is collected alcohol eluen, and concentrate drying gets Radix Isatidis total phenylpropanoid position 15g, and it is 64.4% that ultraviolet spectrophotometry records total phenylpropanoid content;
(2) get Radix Isatidis medical material 1Kg, extract twice with 10 times of amount 70% alcohol heating reflux, each 1h, reclaim ethanol, merge extractive liquid, concentrates, concentrate to add concentration be 5% dissolving with hydrochloric acid, filter acid extraction thing and acid non-soluble substance, the acid extraction thing concentrates last 732 storng-acid cation exchange resins in back and adsorbs, successively water and alkaline alcohol solution eluting, collecting concentration is 10%～90% alkaline ethanol eluting position, concentrate last 717 strong-base anion-exchange resins, absorption impurity, collect effluent, concentrate drying gets Radix Isatidis total alkaloids position 10g, and it is 55.57% that acid-base titrations records total alkaloid content; Acid non-soluble substance is last 717 strong-base anion-exchange resins earlier, wash colourless after, with the acid pure eluting of 1mol/L, eluent transfers to pH 4 after reclaiming alcohol, by 732 storng-acid cation exchange resins, effluent is concentrated, must make with extra care total organic acids position 20g.It is 68.46% that acid-base titrations records organic acid content.
(3) get 30 parts at the Radix Isatidis total phenylpropanoid position that step (1) and (2) prepare, 40 parts at total organic acids position, mix homogeneously promptly gets (lot number 001).
Get above Radix Isatidis active site compositions 10g, add medical starch 6g, mix homogeneously, add water and make soft material, cross 20 mesh sieves and granulate drying, make granule, incapsulate, every 0.2g perhaps gets Radix Isatidis active site compositions 10g, corn starch 5g, add magnesium stearate lubricant 5g, mix homogeneously, tabletting is made tablet then.
Embodiment 2 Radix Isatidis active site preparation of compositions
Step (1) and (2) are with embodiment 1, get 30 parts at the Radix Isatidis total phenylpropanoid position that step (1) and (2) prepare, 40 parts at total organic acids position, and 20 parts at total alkaloids position, mix homogeneously promptly gets (lot number 002).
Get above Radix Isatidis active site compositions 20g, add medical starch 10g, mix homogeneously, add water and make soft material, cross 20 mesh sieves and granulate drying, make granule, incapsulate, every 0.2g perhaps gets Radix Isatidis active site compositions 10g, corn starch 5g, add magnesium stearate lubricant 5g, mix homogeneously, tabletting is made tablet then.Or get above Radix Isatidis active site compositions 10g, and adding medical starch 8g, mix homogeneously is crossed 20 mesh sieve granulate, and drying is made granule.
Embodiment 3 Radix Isatidis active site preparation of compositions
(1) gets Radix Isatidis medical material 1Kg, use 8 times and 6 times of water gaging supersound extraction 2h, 1.5h respectively, merge extractive liquid, is put coldly, filters, reclaim under reduced pressure concentrates, obtain water and carry the position, adopt ultrafiltration membrance filter, molecular cut off 1000～1000000 filtrates, the dry Radix Isatidis total polysaccharides position 48g that gets, it is 60.21% that the phenolsulfuric acid method records total polysaccharides content; Add 95% ethanol in the extracting solution in addition, to the ethanol final concentration be 80%, standing over night filters, filter precipitation and supernatant, D101 macroporous adsorbent resin on the supernatant, first water eluting, reuse concentration 10%～60% alcoholic solution eluting, collect alcohol eluen, concentrate drying gets Radix Isatidis total phenylpropanoid position 17g, and ultraviolet spectrophotometry records total phenylpropanoid content 70.68%;
(2) get Radix Isatidis medical material 1Kg, measure 70% ethanol ultrasonic extraction twice with 10 times, each 1.5h, reclaim ethanol, merge extractive liquid, concentrates, concentrate to add concentration be 5% dissolving with hydrochloric acid, filter acid extraction thing and acid non-soluble substance, the acid extraction thing concentrates last 732 storng-acid cation exchange resins in back and adsorbs, successively water and 1mol/L alkaline ethanol solution eluting, collect alkaline ethanol eluting position, concentrate last 717 strong-base anion-exchange resins, absorption impurity, collect the effluent part, concentrate drying gets Radix Isatidis total alkaloids position 11g, and it is 60.57% that acid-base titrations records total alkaloid content; Acid non-soluble substance is last 717 strong-base anion-exchange resins earlier, wash colourless after, with the acid pure eluting of 1mol/L, eluent transfers to pH 4 after reclaiming alcohol, by 732 storng-acid cation exchange resins, effluent is concentrated, must make with extra care total organic acids position 23g.It is 75.46% that acid-base titrations records organic acid content.
(3) get 60 parts at the Radix Isatidis total phenylpropanoid position that step (1) and (2) prepare, 40 parts at total alkaloids position, 80 parts at total organic acids position, 80 parts at total polysaccharides position, mix homogeneously promptly gets (lot number 003).
Get above Radix Isatidis active site compositions 10g, add medical starch 6g, mix homogeneously, add water and make soft material, cross 20 mesh sieves and granulate drying, make granule, incapsulate, every 0.2g perhaps gets Radix Isatidis active site compositions 10g, corn starch 5g, add magnesium stearate lubricant 5g, mix homogeneously, tabletting is made tablet then.
Embodiment 4 Radix Isatidis active site preparation of compositions
Step (1) and (2) are with embodiment 3, get 60 parts at the Radix Isatidis total phenylpropanoid position that step (1) and (2) prepare, and the 90 parts of mix homogeneously in total organic acids position promptly get (lot number 004).
Get above Radix Isatidis active site compositions 100g, add medical starch 60g, mix homogeneously, add water and make soft material, cross 20 mesh sieves and granulate drying, make granule, incapsulate, every 0.2g perhaps gets Radix Isatidis active site compositions 100g, corn starch 50g, add magnesium stearate lubricant 30g, mix homogeneously, tabletting is made tablet then.Or get above Radix Isatidis active site compositions 100g, and adding medical starch 60g, mix homogeneously is crossed 20 mesh sieve granulate, and drying is made granule.
Embodiment 5 Radix Isatidis active site preparation of compositions
Step (1) and (2) are with embodiment 3, get 40 parts at the Radix Isatidis total phenylpropanoid position that step (1) and (2) prepare, 80 parts at total organic acids position, 80 parts at total alkaloids position, and mix homogeneously promptly gets (lot number 005).
Get above Radix Isatidis active site compositions 10g, add medical starch 6g, mix homogeneously, add water and make soft material, cross 20 mesh sieves and granulate drying, make granule, incapsulate, every 0.2g perhaps gets Radix Isatidis active site compositions 10g, corn starch 5g, add magnesium stearate lubricant 5g, mix homogeneously, tabletting is made tablet then.Or get above Radix Isatidis active site compositions 10g, and adding medical starch 6g, mix homogeneously is crossed 20 mesh sieve granulate, and drying is made granule.
Embodiment 6 Radix Isatidis active site preparation of compositions
Step (1) and (2) are with embodiment 3, get 60 parts at the Radix Isatidis total phenylpropanoid position that step (1) and (2) prepare, 20 parts at total alkaloids position, 40 parts at total organic acids position, and 40 parts at total polysaccharides position, mix homogeneously promptly gets (lot number 006).
Get above Radix Isatidis active site compositions 10g, add medical starch 6g, mix homogeneously, add water and make soft material, cross 20 mesh sieves and granulate drying, make granule, incapsulate, every 0.2g perhaps gets Radix Isatidis active site compositions 10g, corn starch 5g, add magnesium stearate lubricant 5g, mix homogeneously, tabletting is made tablet then.Or get above Radix Isatidis active site compositions 10g, and adding medical starch 6g, mix homogeneously is crossed 20 mesh sieve granulate, and drying is made granule.
Embodiment 7 Radix Isatidis active site preparation of compositions
Step (1) and (2) are with embodiment 3, get 30 parts at the Radix Isatidis total phenylpropanoid position that step (1) and (2) prepare, 10 parts at total alkaloids position, 60 parts at total organic acids position, and 60 parts at total polysaccharides position, mix homogeneously promptly gets (lot number 006).
Get above Radix Isatidis active site compositions 10g, add medical starch 6g, mix homogeneously, add water and make soft material, cross 20 mesh sieves and granulate drying, make granule, incapsulate, every 0.2g perhaps gets Radix Isatidis active site compositions 10g, corn starch 5g, add magnesium stearate lubricant 5g, mix homogeneously, tabletting is made tablet then.Or get above Radix Isatidis active site compositions 10g, and add medical starch 6g, mix all
The interior resisting virus pharmacodynamic study of embodiment 8 Radix Isatidis active site compositionss
1 experiment material
1.1 be subjected to the reagent thing
Embodiment 1 gained lot number 001, embodiment 2 gained lot numbers 002, embodiment 3 gained lot numbers 003, embodiment 4 gained lot numbers 004, the active component composition of embodiment 5 gained lot numbers 005 and embodiment 6 gained lot numbers 006.
1.2 experiment reagent and instrument
Radix Isatidis granule (Henan Province Wanxi Pharmacy Stock Co., Ltd, lot number: 20090102); Ribavirin tablet (Meidakang Pharmaceutical Co., Ltd., Sichuan Prov., lot number: 090627); Ether (Nanjing chemical reagent work, lot number: 090601); Chicken red blood cell (fresh cock blood is with standby after the normal saline washing three times); Sodium chloride (chemical plant, granary, lot number: 20080429); Picric acid (Shanghai chemical reagent purchasing and supply station, lot number: 090123); Embryo Gallus domesticus (9-11 age in days) (Nanjing Zhongmu Stocks Trading Co. medical instruments factory); FA1004 electronic analytical balance (Shanghai balance factory); Clean work station (Suzhou Decontamination Equipment Plant); Incubator (Shanghai analytical tool factory); 24 hole microwell plates (U.S. corning company).
1.3 experiment is with viral
Influenza A virus A/PR8/34 (H1N1) is provided by Virology Inst., China Academy of Preventive Medicine Sciences.
1.4 laboratory animal
ICR level mice ♀
Dual-purpose (is provided the quality certification number: SCXK2007-0001) by Yangzhou University's Experimental Animal Center.
1.5 test feedstuff
Full nutrition pellet: provide by the collaborative medical biotechnology company limited in Jiangsu Province.
1.6 experiment condition
ICR level mice random packet, sub-cage rearing are freely drunk water, and feed full-valence pellet feed, 22 ± 2 ℃ of room temperatures, humidity 55-65%.
1.7 experimental drug preparation
Ribavirin granule: 100mg/ bag and 20ml normal saline, it is standby to be made into 5mg/ml;
Radix Isatidis granule: 5g/ bag and 10ml normal saline, it is standby to be made into 0.5g/ml;
The active site compositions: lot number 001, lot number 003, lot number 005 are mixed with the concentration of 1.5g/ml respectively with CMC-Na solution by the weight of active site; Lot number 002, lot number 004, lot number 006 are mixed with the concentration of 2.0g/ml respectively with CMC-Na solution by the weight of active site.
Single active site: Radix Isatidis total phenylpropanoid position is mixed with the concentration of 1.5g/ml with CMC-Na solution; The total alkaloids position is mixed with the concentration of 1.0g/ml with CMC-Na solution; The total organic acids position is mixed with the concentration of 2.0g/ml with CMC-Na solution; The total polysaccharides position is mixed with the concentration of 2.0g/ml with CMC-Na solution.
1.8 experiment statistics method
Statistics adopt t check, X 2 test.
2. experimental technique and result
2.1 the influenza A virus Embryo Gallus domesticus increases the poison test
Get 9 instar chicken embryos, labelling air chamber on egg candler is placed in the aseptic clean bench, sterilizes respectively after 2 times with 75% ethanol and 2% iodine tincture, grinds an osculum in air chamber barrier film place gently with aseptic emery wheel, about 0.05cm diameter (being the needle point size).
Get influenza A virus (powdery), gradation adds the 0.3ml normal saline 2-3 time, and behind the mixing, sucking-off is put in the sterile test tube, and is diluted to 2ml, and after the piping and druming, each egg inoculation 0.2ml influenza A virus is put and cultivated 48h in 37 ℃ of calorstats.
More than after instar chicken embryo on the 9th cultivates 48h, put into 4 ℃ of refrigerators, vessel inner blood is solidified, take out next day, put in the super-clean bench, after 75% ethanol and the sterilization of 2% iodine tincture, remove sealing part paraffin with aseptic nipper, remove air chamber and membrane layer with tweezers, increase poison allantoic fluid once with being collected as more than the aseptic straw gentle aspiration allantoic fluid (discarding muddy allantoic fluid).After more than test repeats 3 times, be used for experiment, do hemagglutination test before the experiment.
2.2 hemagglutination test
Get 24 hole microwell plates, every hole adds normal saline 0.5ml, (the 1st pipe adds NS 0.9ml), with allantoic fluid numbering (with every Embryo Gallus domesticus), getting allantoic fluid 0.1ml adds and takes out 0.5ml behind the 1st pipe mixing and add in second pipe, be diluted to the 8th pipe successively, the 9th pipe does not add virus, do blank (normal saline), get fresh cock blood (crowing) subsequently and shake up after 0.5% chicken red blood cell solution (normal saline) 0.25ml adds gently, put room temperature and place observed and recorded behind the 2h with being made into after the normal saline washing 3 times.
Observation caliber:
++ ++: one deck erythrocyte is the propagation shape and evenly is laid on the pipe end
+++: is the same substantially, but the edge is thinner
++: blood cell forms a ring-type in the pipe end, but little coagulation piece is arranged all around
+: blood cell forms little group in the pipe end, and the edge is rough neat
-: blood cell is sunken to pipe and forms little group in the end, and the edge is smooth neat
Experimental result is judged: 2,4,5,6, the 8 blood clotting titration of collecting allantoic fluid are more than 640, can be used for infecting mouse in the body.
2.3 influenza a virus infection mice lethal dose (LD
50) measure
Get 56 of ICR mices, body weight 13-16g, male and female half and half are divided 7 groups at random, and 8 every group, get and increase 3 viral allantoic fluids of poison, with 10 times of dilutions, every group drips with each virus concentration, observes death toll in the 14d, press the calculating of Reed Muench method.Result: press Reed Muench method and calculate LD
50=1.71, influenza A virus LD
50=10
-1.71
2.4 the Radix Isatidis compositions is to the dead protective effect of influenza a virus infection mice
Get 240 of ICR mices, body weight 13-16g, male and female half and half are divided into 12 groups at random, 20 every group.The equal gastric infusion of each treated animal, dosage 10ml/kg, once a day, continuous 7d.Administration same day, each organizes mice under the shallow degree anesthesia of ether, gives the infection of mice collunarium, every Mus 30 μ l with the influenza A virus allantoic fluid of blood clotting titre 640 or more.Observe zoogenetic infection influenza A virus sequela and death condition, death toll in the record 14d, and compare between organizing, calculate mortality rate, survival natural law, survival rate.Concrete experimental result the results are shown in Table 1.
Table 1 Radix Isatidis compositions is to the protection of influenza A virus A/PR8/34 infecting mouse death
Group dosage number of animals death toll protective rate survival natural law
(g/kg) (only) (only) (%) (d)
Model group equivalent NS 20 19 5 5.20 ± 2.33
Ribavirin granule group 0.05 20 11 45* 10.10 ± 3.72**
Radix Isatidis granule group 10.00 20 15 25 7.50 ± 3.94*
Compositions lot number 001 1.50 20 12 40* 9.00 ± 4.28**
Compositions lot number 002 2.00 20 11 45* 9.40 ± 3.89**
Compositions lot number 003 1.50 20 12 40* 8.80 ± 3.99**
Compositions lot number 004 2.00 20 13 35* 8.75 ± 4.09**
Compositions lot number 005 1.50 20 14 30* 9.05 ± 4.64**
Compositions lot number 006 2.00 20 14 30* 8.25 ± 3.78**
Total phenylpropanoid group 1.50 20 16 20 7.35 ± 3.60
Total alkaloids group 2.00 20 17 15 6.35 ± 3.42
Total organic acids group 2.00 20 16 20 7.15 ± 3.50
Total polysaccharides group 2.00 20 18 10 6.05 ± 4.06
(
*P＜0.05;
*Compare with model group P＜0.01)
Shown in table 1 experimental result: 001 group of Radix Isatidis active site compositions lot number, 002 group of lot number, 003 group of lot number, 004 group of lot number, 005 group of lot number and lot number can obviously prolong influenza A virus (H for 006 group
1N
1) survival natural law behind the infecting mouse, relatively have notable difference (P＜0.01) with model group.001 group, 002 group, 003 group, 004 group, 005 group of Radix Isatidis component composite lot number and 006 group are to influenza A virus (H
1N
1) protective effect of mice infected is stronger, relatively has significant difference (P＜0.05) with model group.And the experimental result contrast shows, active site compositions provided by the invention is compared with one total phenylpropanoid, total alkaloids, total organic acids or total polysaccharides has better antivirus action, after showing each active component scientific matching, antiviral activity strengthens, each active component has played the effect of Synergistic, can many target spots multipath performance antivirus action.
The antibiotic pharmacodynamic study of embodiment 9 Radix Isatidis active site compositionss
1 experiment material
1.1 be subjected to the reagent thing
Embodiment 1 gained lot number 001, embodiment 2 gained lot numbers 002, embodiment 3 gained lot numbers 003, embodiment 4 gained lot numbers 004, the active component composition of embodiment 5 gained lot numbers 005 and embodiment 6 gained lot numbers 006.
1.2 experiment reagent and instrument
Radix Isatidis granule (by the self-control of pharmacopeia method): 1g is equivalent to crude drug 2.86g; Dimethyl sulfoxide (analytical pure) (Chemical Reagent Co., Ltd., Sinopharm Group, T20080711); Peptone (OXOID LP0042, OXOID LID.BASINGSTOKE, HAMPSHIRE); Carnis Bovis seu Bubali cream (Chemical Reagent Co., Ltd., Sinopharm Group, F20080107); Sodium chloride (analytical pure) (Shantou Xilong Chemical Factory, Guangdong, 080719); Agar powder (purification) (Chemical Reagent Co., Ltd., Sinopharm Group, KS20080322).
Oxford cup (stainless steel tube, internal diameter 6mm, external diameter 8mm, high 10mm), culture dish (size is consistent, and is smooth at the bottom of the ware for diameter 90mm, dark 20mm), test tube with ground stopper, conical flask, dropper, inoculating loop, spreader, liquid-transfering gun, tweezers, slide gauge.Spectrum752 type ultraviolet-uisible spectrophotometer (Shanghai Spectrum Apparatus Co., Ltd.); Portable pressure steam sterilizer (Shanghai Huaxian Medical Nuclear Instruments Co., Ltd.); PYX-DHS-40X50-S-II type water isolation type electro-heating standing-temperature cultivator (Shanghai make a leapleap forward medical apparatus and instruments factory); The desk-top constant temperature oscillator of Hua Lida HZ-9201K type (Taicang science and education equipment factory); The dual-purpose clean work station of the single horizontal vertical of SW-CJ-1FB type (Purifying Equipment Co., Ltd., Suzhou).
1.3 experiment bacterial strain
Staphylococcus aureus (ATCC25923), escherichia coli (ATCC25922), blue pus organism (ATCC27853), bacillus subtilis (ACCC11060) is all available from the biological health technology company limited of Nanjing BDCom of Jiangsu Province Disease Control and Prevention Center.
1.4 culture medium preparation
Fluid medium: general culture medium: peptone 10g, Carnis Bovis seu Bubali cream 5g, sodium chloride 5g, agar powder (high-quality) 12g, distilled water 1L.Mentioned component (except that agar) is soluble in water, behind the correction pH 7.2～7.4, boil dissolving, carry out packing according to the purposes difference, through 121 ℃ of sterilization 15min, to pour in the wide-mouth conical flask, cold preservation is standby.Solid medium: general culture medium: peptone 10g, Carnis Bovis seu Bubali cream 5g, sodium chloride 5g, agar powder (high-quality) 12g, distilled water 1L.Mentioned component (except that agar) is soluble in water, proofread and correct pH 7.2～7.4 backs and add agar, boil dissolving, carry out packing according to the purposes difference, through 121 ℃ of sterilization 15min, pour plate or bevel, cold preservation is standby.
1.5 experimental drug preparation
Bacteriostatic test Radix Isatidis granule: high concentration: be made into 1500gL with DMSO
-1Standby; Low concentration: be made into 300gL with DMSO
-1Standby.Each extract is mixed with the amount (seeing Table 2) that is equivalent to Radix Isatidis granule by the conversion of effective site extraction ratio with DMSO.
2 experimental techniques and result
The Radix Isatidis compositions is mixed with respective concentration, carries out the mensuration of inhibition zone DD value with the agar plate diffusion method.At first, be 2 * 10 with concentration
8CFUml
-1Bacterium liquid 0.1-0.2ml be coated in equably on the flat board, place the Oxford cup then, with liquid-transfering gun 10 μ L samples are injected and scribble on the flat board of bacterium liquid.After placing 37 ℃ of incubators to cultivate 24h the flat board, measure the antibacterial circle diameter size.Each strain repeats 3 times and measures results averaged.The negative contrast of DMSO.Concrete experimental result is as shown in table 2:
The fungistatic effect of table 2 Radix Isatidis compositions
Show by table 2 experimental result: 001 group of Radix Isatidis compositions, 002 group, 003 group, 004 group, the height of 005 group and 006 group, low concentration all has fungistatic effect in various degree, but single Radix Isatidis total phenylpropanoid of using, the total alkaloids group, the total organic acids group, then fungistatic effect is relatively poor for total polysaccharides group and Radix Isatidis granule group, especially when low concentration, Radix Isatidis granule group and total alkaloids, single position group of total polysaccharides does not almost demonstrate fungistatic effect, after further showing active component scientific matching provided by the invention, played the effect of Synergistic, fungistatic effect obviously strengthens.
The analgesic pharmacodynamic study of embodiment 10 Radix Isatidis active site compositionss
1 experiment material
1.1 be subjected to the reagent thing
Embodiment 1 gained lot number 001, embodiment 2 gained lot numbers 002, embodiment 3 gained lot numbers 003, embodiment 4 gained lot numbers 004, the active component composition of embodiment 5 gained lot numbers 005 and embodiment 6 gained lot numbers 006.
1.2 experiment reagent
Radix Isatidis granule (by the self-control of pharmacopeia method): 1g is equivalent to crude drug 2.86g; Angel high activity dried yeast (Hubei Angel Yeast Co.,Ltd, lot number 20100122) preparation (10%) of experiment dry yeast suspension on the same day: take by weighing dry yeast 20g in mortar, slowly add distilled water and be ground to outstanding uniformly slurry, last standardize solution is 200mL; The preparation of endotoxin (LPS lipopolysaccharide (Sigma)) endotoxin solution: it is some that precision balance takes by weighing endotoxin, is 1.5mg10ml with the dilution of injection physiological saline solution
-1Aspirin Enteric-coated Tablets (Baijingyu Pharmaceutical Co., Ltd., Nanjing, lot number 090202) is mixed with 20.5mgml
-1Solution.
1.3 animal for research
The SD rat, all male, body weight 180～220g (is provided the quality certification number: SCXK2008-0033) by Zhejiang Province's Experimental Animal Center.
1.4 experimental drug preparation
Separate heat test: Aspirin Enteric-coated Tablets: be made into 20.5mgml with distilled water
-1Standby; Radix Isatidis granule: be made into 1gml with normal saline
-1Standby; Each compositions is mixed with the amount (seeing Table 3～table 4) that is equivalent to Radix Isatidis granule by the conversion of effective site extraction ratio with CMC-Na solution.
2 experimental techniques and result
2.1 the Radix Isatidis compositions causes the refrigeration function of rat fever model to dry yeast
Male rat is predicted body temperature 3～4 days in laboratory environment, the same day was measured intact animal's anus temperature 2～3 times in experiment, get its meansigma methods as basal body temperature, with 37.5～38.5 ℃ of body temperature, ≤ 0.4 ℃ of person of body temperature fluctuation is the qualified rat that is for experiment, every rat is in back subcutaneous injection 10% dry yeast suspension (10mLkg-1), raising than basal body temperature behind the 6h, the person elects the heating Mus as more than 1.0 ℃, be divided into 13 groups at random, each organizes 8, all adopt disposable gastric infusion (Radix Isatidis granule group 10gkg-1), positive group gives aspirin (410mgkg-1), and model control group gives the physiological solution with volume.An each compositions and Ge Dang extract is pressed table 3 dosage gastric infusion, respectively at after the administration 1,2,3,4h measures rat anus temperature, is that index is organized a t check with body temperature after each treated animal administration.Concrete experimental result is as shown in table 3:
Table 3 Radix Isatidis compositions causes the refrigeration function of rat fever model to dry yeast
*: compare * p≤0.05, * * p≤0.01 with model group;
#: compare #p≤0.05, ##p≤0.01 with total alkaloids position group
2.2 the Radix Isatidis compositions causes the refrigeration function of rat fever model to endotoxin
Male rat is predicted body temperature 3～4 days in laboratory environment, the same day was measured intact animal's anus temperature 2～3 times in experiment, get its meansigma methods as basal body temperature, with 37.5～38.5 ℃ of body temperature, ≤ 0.4 ℃ of person of body temperature fluctuation is the qualified rat that is for experiment, be divided into 13 groups at random, each organizes 8, every rat is in lumbar injection endotoxin (40 μ gkg-1), all adopt disposable gastric infusion (Radix Isatidis granule group 10gkg-1) afterwards, positive group gives aspirin (410mgkg-1), and model control group gives the physiological solution with volume.An each compositions and Ge Dang extract is pressed table 4 dosage gastric infusion, respectively at after the administration 1,2,3,4,6h measures rat anus temperature, is that index is organized a t check with body temperature after each treated animal administration.Concrete experimental result is as shown in table 4:
Table 4 Radix Isatidis extract causes the refrigeration function of rat fever model to endotoxin
*: compare * p≤0.05, * * p≤0.01 with model group;
#: compare #p≤0.05, ##p≤0.01 with total alkaloids position group
Experimental result by above table 3 and table 4 shows: compare with model group, 001 group of Radix Isatidis component composite lot number, 002 group, 003 group, 004 group, 005 group and 006 group all has significant refrigeration function (p≤0.05, p≤0.01), and with the single total phenylpropanoid of Radix Isatidis, total alkaloids, total organic acids is compared with total polysaccharides, each active ingredient compositions provided by the invention has shown more superior refrigeration function, and part compositions lot number 1,2,3 show and the approaching refrigeration functions of positive drug aspirin, have played synergistic function after further proving compositions scientific matching provided by the invention.
Show by above antiviral, antibiotic, analgesic experimental result, each active site compositions of Radix Isatidis provided by the invention, each ingredient proportioning is scientific and reasonable, show by contrast and experiment, compositions provided by the invention is not the stack of the simple amount of each component, reached the effect of Synergistic after the proportioning, many target spots multipath performance antiviral and antibiotic, refrigeration function.Radix Isatidis active site compositions provided by the invention has antiviral, antimicrobial antiphlogistic is conciliate the heavy pharmacologically active of overabundant heat, can be used for the treatment that viral disease merges antibacterial inflammation fever diseases, and clinical application range is more extensive.
Above embodiment only is explanation technical conceive of the present invention and characteristics; its purpose is to allow the people that is familiar with this technology understand content of the present invention and is implemented; can not limit protection scope of the present invention with this; all equivalences that spirit is done according to the present invention change or modify, and all should be encompassed in protection scope of the present invention.
Claims (10)
1. Radix Isatidis active site compositions, it is characterized in that: it is made up of following raw materials according: Radix Isatidis total phenylpropanoid position and Radix Isatidis total organic acids position.
2. Radix Isatidis active site compositions according to claim 1, it is characterized in that: it is made up of the raw material of following parts by weight:
10～90 parts at Radix Isatidis total phenylpropanoid position, 10～90 parts at Radix Isatidis total organic acids position.
3. Radix Isatidis active site compositions, it is characterized in that: it is made up of the raw material of following parts by weight:
10～90 parts at Radix Isatidis total phenylpropanoid position, 10～90 parts at Radix Isatidis total organic acids position, 10～90 parts at Radix Isatidis total alkaloids position.
4. Radix Isatidis active site compositions, it is characterized in that: it is made up of the raw material of following parts by weight:
10～90 parts at Radix Isatidis total phenylpropanoid position, 10～90 parts at Radix Isatidis total organic acids position, 10～90 parts at Radix Isatidis total alkaloids position, 10～90 parts at Radix Isatidis total polysaccharides position.
5. Radix Isatidis active site compositions according to claim 4 is characterized in that: described Radix Isatidis total phenylpropanoid position is the Radix Isatidis extract that contains percentage by weight 50%～100% total phenylpropanoid; Radix Isatidis total organic acids position is the Radix Isatidis extract that contains percentage by weight 50%～100% total organic acids; Radix Isatidis total alkaloids position is the Radix Isatidis extract that contains percentage by weight 50%～100% total alkaloids; Radix Isatidis total polysaccharides position is the Radix Isatidis extract that contains percentage by weight 50%～100% total polysaccharides.
6. according to each described Radix Isatidis active site compositions of claim 1 to 5, it is characterized in that: the medicine of Radix Isatidis active site compositions and pharmaceutically acceptable carrier being made capsule, tablet, drop pill, granule, injection, encapsulated form.
7. claim 2,3 or 4 described Radix Isatidis active site preparation of compositions methods is characterized in that may further comprise the steps:
(1) Radix Isatidis with the Isatis indigotica Fort. platymiscium is a raw material, adopts solvent extraction method, gets extracting solution, and extracting solution adopts ultrafiltration membrance filter, molecular cut off 1000～1000000 parts, the dry Radix Isatidis total polysaccharides that gets; Or adding alcohol makes determining alcohol reach 30～90% in the extracting solution, place precipitation, filter precipitation and supernatant, precipitate dry Radix Isatidis total polysaccharides position, macroporous adsorbent resin on the supernatant, the first water eluting of getting, reuse concentration 10%～60% alcoholic solution eluting, collect alcohol eluen, concentrate drying gets Radix Isatidis total phenylpropanoid position;
(2) Radix Isatidis with the Isatis indigotica Fort. platymiscium is a raw material, adopts solvent extraction method, gets extracting solution, concentrate, concentrate adds acid extraction, filter acid extraction thing and acid non-soluble substance, the acid extraction thing concentrates the back and goes up cationic exchange resin adsorption, and water and alkaline alcohol solution eluting are collected 10%～90% alkaline alcohol eluting position successively, concentrate, last anion exchange resin, absorption impurity is collected effluent, concentrate drying gets Radix Isatidis total alkaloids position; Anion exchange resin absorption on the acid non-soluble substance, water and acidity alcohol solution eluting are collected 10%～90% acid pure eluting position successively, concentrate, cation exchange resin on the concentrate, absorption impurity is collected effluent, concentrate, drying gets Radix Isatidis total organic acids position;
(3) choose Radix Isatidis total phenylpropanoid position, total organic acids position and/or total alkaloids position and/or total polysaccharides position in claim 2,3 or 4 described ratios, mix homogeneously, promptly.
8. Radix Isatidis active site preparation of compositions method according to claim 7, it is characterized in that: solvent extraction method in step (1) and (2), selecting for use and extracting solvent is that water or concentration are 30%～100% methanol, ethanol, propanol, butanols, amylalcohol, acetone, ethyl acetate or Ethyl formate or their mixed solvent, and extracting method is dipping extraction method, ultrasonic extraction or heating and refluxing extraction method.
9. Radix Isatidis active site preparation of compositions method according to claim 7 is characterized in that: macroporous adsorbent resin is oleic series or styrene series resin in the step (1).
10. the application of each described Radix Isatidis active site compositions of claim 1 to 5 in preparation antiviral, antibiotic, antipyretic analgesics.。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102699544A CN101933966B (en) | 2010-08-31 | 2010-08-31 | Active site composition of isatis roots, as well as preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102699544A CN101933966B (en) | 2010-08-31 | 2010-08-31 | Active site composition of isatis roots, as well as preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101933966A true CN101933966A (en) | 2011-01-05 |
| CN101933966B CN101933966B (en) | 2011-12-21 |
Family
ID=43387687
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102699544A Expired - Fee Related CN101933966B (en) | 2010-08-31 | 2010-08-31 | Active site composition of isatis roots, as well as preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101933966B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102614206A (en) * | 2011-01-31 | 2012-08-01 | 澳门科技大学 | Application of 7S,8R,8'R-(+)-lariciresinol-4,4'-bi-O-beta-D-glucopyranoside in preparing medicines |
| CN103288973A (en) * | 2012-03-02 | 2013-09-11 | 中国人民解放军军事医学科学院毒物药物研究所 | Isatis root polysaccharides, and preparation method and use thereof |
| CN104840477A (en) * | 2015-04-20 | 2015-08-19 | 广州医科大学附属第一医院 | Drug application of lariciresinol-4-O-beta-D-glucoside and pharmaceutical composition thereof |
| CN111202732A (en) * | 2020-02-18 | 2020-05-29 | 广州医科大学附属第一医院 | Application of Caulilexin C in preparation of medicine for preventing or treating influenza A |
| CN112691079A (en) * | 2021-01-27 | 2021-04-23 | 吉林医药学院 | Foot bacteriostatic care solution containing traditional Chinese medicine extract and preparation method thereof |
| CN112999254A (en) * | 2019-12-18 | 2021-06-22 | 沈阳药科大学 | Isatis tinctoria leaf total alkaloid and extraction method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1318399A (en) * | 2000-04-18 | 2001-10-24 | 十堰康迪制药厂 | Radix Isatidis injecta and its preparation |
| CN1520837A (en) * | 2003-01-30 | 2004-08-18 | 普文英 | Plant extract and compound for treating endotoxin blood disease, and its extraction method and application |
| CN1666984A (en) * | 2004-03-12 | 2005-09-14 | 徐丽华 | Process for extracting epigoitrin from isatis root and use thereof |
-
2010
- 2010-08-31 CN CN2010102699544A patent/CN101933966B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1318399A (en) * | 2000-04-18 | 2001-10-24 | 十堰康迪制药厂 | Radix Isatidis injecta and its preparation |
| CN1520837A (en) * | 2003-01-30 | 2004-08-18 | 普文英 | Plant extract and compound for treating endotoxin blood disease, and its extraction method and application |
| CN1666984A (en) * | 2004-03-12 | 2005-09-14 | 徐丽华 | Process for extracting epigoitrin from isatis root and use thereof |
Non-Patent Citations (2)
| Title |
|---|
| 《中草药》 20080430 安益强等 板蓝根抗病毒物质基础研究思路 第39卷, 第4期 2 * |
| 《时珍国医国药》 20061231 武佳等 板蓝根化学成分及质量控制研究 第17卷, 第10期 2 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102614206A (en) * | 2011-01-31 | 2012-08-01 | 澳门科技大学 | Application of 7S,8R,8'R-(+)-lariciresinol-4,4'-bi-O-beta-D-glucopyranoside in preparing medicines |
| CN103288973A (en) * | 2012-03-02 | 2013-09-11 | 中国人民解放军军事医学科学院毒物药物研究所 | Isatis root polysaccharides, and preparation method and use thereof |
| CN103288973B (en) * | 2012-03-02 | 2015-12-02 | 北京中安佐际生物科技有限公司 | Banlangen Polysaccharide, Preparation Method And The Use |
| CN104840477A (en) * | 2015-04-20 | 2015-08-19 | 广州医科大学附属第一医院 | Drug application of lariciresinol-4-O-beta-D-glucoside and pharmaceutical composition thereof |
| CN104840477B (en) * | 2015-04-20 | 2019-01-25 | 广州医科大学附属第一医院 | Lariciresinol -4-O- β-D-Glucose glycosides medicinal application and its pharmaceutical composition |
| CN112999254A (en) * | 2019-12-18 | 2021-06-22 | 沈阳药科大学 | Isatis tinctoria leaf total alkaloid and extraction method and application thereof |
| CN111202732A (en) * | 2020-02-18 | 2020-05-29 | 广州医科大学附属第一医院 | Application of Caulilexin C in preparation of medicine for preventing or treating influenza A |
| CN112691079A (en) * | 2021-01-27 | 2021-04-23 | 吉林医药学院 | Foot bacteriostatic care solution containing traditional Chinese medicine extract and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101933966B (en) | 2011-12-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101933966B (en) | Active site composition of isatis roots, as well as preparation method and application thereof | |
| CN103156826B (en) | The purposes of patchouli alcohol | |
| CN101919961B (en) | Drug composition for treating cold and preparation method thereof | |
| CN1730015A (en) | Honey suckle extract and its preparing process and application | |
| CN102688332B (en) | A kind of Chinese medicine composition for the treatment of flu and preparation method thereof | |
| CN101129455B (en) | Sophora extractive and method of preparing the same and application of the same | |
| CN103182049A (en) | Preparation method of pharmaceutical composition preparation treating apoplexy sequelae | |
| CN114053343A (en) | Traditional Chinese medicine composition, preparation method and application | |
| CN108926584A (en) | The antimicrobial purposes of chimonanthea extract | |
| CN101700290B (en) | Pharmaceutical composition for preventing and treating warm-heat diseases of livestock and poultry and preparation method thereof | |
| CN103768157A (en) | Veterinary antiviral traditional Chinese medicine Ziqi effervescent granules and preparation method thereof | |
| CN102397333A (en) | Preparation and quality detection methods of honeysuckle flower-baikal skullcap root injection | |
| CN104306492A (en) | Drug with anti-bacterial and synergistically anti-bacterial activity, and preparation method and application thereof | |
| CN104800276A (en) | Veterinary codonopsis pilosula atractylode and astragalus Chinese medicine preparation | |
| CN101606991A (en) | The technology of preparing fugui ostealgia compound by microorganism fermentation method | |
| CN101411752A (en) | Granular formulation for treating children's pneumonia | |
| CN101244165B (en) | Tablet for treating damp-heat gonorrhoea and preparation thereof | |
| CN1939412B (en) | Medicinal composition with dauricine and houttuynin sodium | |
| CN103936812B (en) | Lupinane type triterpene compound and pharmaceutical composition thereof are applied with it | |
| CN101744883A (en) | Chinese medicinal composition preparation and preparation method thereof and quality control method | |
| CN102600120B (en) | Application of cinnamic acid in preparation of drugs for preventing and treating livestock and poultry virus infection | |
| CN105001275B (en) | With antiviral activity and the alkaloid c-glycosides of antibacterial activity and its application | |
| CN108992478A (en) | The application of Aralia wood extract in medicine preparation | |
| CN108926583A (en) | The purposes of Zhejiang wintersweet anti-microbial infection | |
| CN102078529B (en) | Chinese medicinal preparation for treating common cold in children |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20111221 Termination date: 20180831 |