Technical field

The present invention relates to the purposes of arteannuin and derivative dihydro-abrotine thereof, Artemether, arteether, artesunate, relate in particular to the purposes in pharmaceutical field.

Background technology

Bacterial infection is present clinical patient main causes of death.During organism infection, antibacterial thalline composition such as genomic DNA and bacterial endotoxin (LPS) are by activating panimmunity cells such as mammal Monocytes, dendritic cell, induce the release of proinflammatory cytokines such as TNF-α, IL-1, IL-6, NO, cause the damage of histoorgan, cause pyemic generation.

Herba Artemisiae Annuae belongs to feverfew, and China scientific research personnel in 1972 separates from the Chinese medicine Herba Artemisiae Annuae the earliest and obtains malaria effective monomer, called after arteannuin.The arteannuin molecular formula is C15H22O5, and according to chemical reaction, spectroscopic data and x-ray list product diffraction method prove that arteannuin is a kind of sesquiterpene lactone with peroxy.The chemical structural formula that its derivant mainly contains dihydroartemisinine, Artemether, arteether and artesunate is:

 

Arteannuin and derivant thereof are used for treating the relevant heating of malaria the history in more than 1,000 year, is mainly used in the drug resistance pernicious malaria now clinically.Efferth TM, Wang X, Huong SM, Hauber I etc. are at its article " Antiviral activity of artesunate towards wild-type, recombinantandganciclovir-resistant human cytomegalovimses " (J Mol Med.2002; 80 (4): described Herba Artemisiae Annuae class material p223-224) and also had the effect of others, as relieving asthma, anticancer, schistosomicide and to immune adjusting etc.The research of relevant arteannuin and derivant thereof both at home and abroad mainly concentrates on malaria, anticancer, antischistosomal effect and the mechanism thereof.

To the existing research of the antiendotoxic effect of arteannuin and derivant thereof, Aldieri E, Bergandi L, RigantiC, Costamagna C, Bosia A, Ghigo D etc. are at its article " Artemisinin inhibits inducible nitricoxide synthase and nuclear factor NF-kB activation " (FEBS Lett.2003; 552 (2-3): described the activation that arteannuin can suppress the synthetic and NF-κ B of LPS/TNF-α inductivity NO synthase p141-144); The beam Aiwa, Xue Baoyun, Li Chunying etc. are at its article " artesunate is to the synthetic inhibitory action of the nitric oxide of endotaxin induction " (CHINA JOURNAL OF CHINESE MATERIA MEDICA .2001; 26 (11): described p770-773.) the artemisinin derivative artesunate to LPS and merge that interferon stimulates Turnover of Mouse Peritoneal Macrophages NO synthetic the obvious suppression effect arranged, the Turnover of Mouse Peritoneal Macrophages RAW264.7 that LPS is stimulated also has similar protective effect, and along with the increase artesunate of artesunate concentration also strengthens the synthetic inhibitory action of NO, beam Aiwa, Xue Baoyun, Wang Jinhua etc. are at its article " artesunate is to the synthetic inhibiting research of the inflammatory factor of endotaxin induction " (Chinese combination of Chinese and Western medicine first aid magazine .2001; 8 (5): inductive TNF-α generation has the obvious suppression effect to LPS at 25～100mg/L to have described artesunate p262.-265), and using the comparison suppression ratio separately with LPS is 43%～58%; Tan Yuqing etc. are at its article " the real research of arteannuin extract anti-endotoxin effect " (CHINA JOURNAL OF CHINESE MATERIA MEDICA .1999; 24 (3): p166-171) find that also Herba Artemisiae Annuae extract, arteannuin can reduce endotoxin shock mice LPO, ACP, endotoxin, TNF-α, P450 concentration; the increased SOD activity; reduce mouse death rate; prolong the mean survival time of mice, Mouse Liver, lung tissue form are also had the certain protection effect.But whether arteannuin and derivant thereof be effective to the sepsis that DNA of bacteria and antibacterial (gram positive bacteria and gram-negative bacteria) cause, and do not appear in the newspapers.

Summary of the invention

The new purposes that the purpose of this invention is to provide a kind of arteannuin and derivative dihydro-abrotine thereof, Artemether, arteether, artesunate, i.e. new application in pharmacy.

In fact, the present invention relates to the application in the medication for treating pyemia that arteannuin and derivative dihydro-abrotine thereof, Artemether, arteether, artesunate cause as preparation prevention or treatment antibacterial.

Relate to arteannuin and derivative dihydro-abrotine thereof, Artemether, arteether, artesunate as the application in the medication for treating pyemia of preparation prevention or treatment CpG ODN initiation.

The present invention relates to the application in the medication for treating pyemia that arteannuin and derivative dihydro-abrotine thereof, Artemether, arteether, artesunate cause as preparation prevention or treatment antibacterial and CpG ODN.

Described CpG ODN is meant the oligonucleotide that includes the CpG motif, is the active least unit of DNA of bacteria.

The applicant has carried out pharmacology's analysis to the extracorporeal anti-inflammatory effect of arteannuin and derivative dihydro-abrotine thereof, Artemether, arteether, artesunate, finds that arteannuin, dihydroartemisinine, Artemether, arteether, artesunate all have the remarkable vitro antiinflammatory action.Arteannuin, dihydroartemisinine, Artemether, arteether, any in the artesunate can significantly suppress colibacillus deactivating inductive people THP-1 cell line and mice RAW264.7 cell line discharges cytokine TNF-α and IL-6, and in therapeutic dose, along with arteannuin, dihydroartemisinine, Artemether, arteether, the increase of any material concentration in the artesunate, inhibitory action also strengthens thereupon, gives arteannuin and derivative dihydro-abrotine thereof in advance, Artemether, arteether, any in the artesunate can have preventive effect.

The applicant is to arteannuin and derivative dihydro-abrotine thereof, Artemether, arteether, antiinflammatory action has carried out pharmacology's analysis in the artesunate body, find arteannuin and derivative dihydro-abrotine thereof, Artemether, arteether, any in the artesunate can both reduce colibacillus deactivating, antibacterial (comprises Grain-negative, positive bacteria) attacks mortality of mice, can significantly suppress mice serum cytokine TNF-α and IL-6 and discharge, and to colibacillus deactivating, main organs (the heart of germ attack mice, liver, intestinal, lung, kidney) has remarkable protective effect; Arteannuin combined with antibiotic treatment bacterial infection effect is better.

Arteannuin and derivative dihydro-abrotine thereof, Artemether, arteether, artesunate use the method for conventional formulation to add the various dosage forms that can be prepared into behind the acceptable carrier medically on the pharmaceutics.

The invention has the advantages that:

(1) the present invention has excavated new medical application to known arteannuin and derivative dihydro-abrotine thereof, Artemether, arteether, artesunate, has opened up a new application.

(2) arteannuin of the present invention and derivative dihydro-abrotine thereof, Artemether, arteether, artesunate safety non-toxic, pharmacological action is strong, and good prospect in medicine is arranged.

(3) big producing country of China's arteannuin and derivant thereof, the present invention has widened the subject range of arteannuin and derivant thereof, has good society and economy benefit.

(4) because present pyemic treatment lacks effective medicine, so the application of arteannuin and derivant thereof is significant to improving pyemic treatment rate.

(5) medicine of material preparation of the present invention has in the significant body and the extracorporeal anti-inflammatory effect, can effectively prevent or treat sepsis.

The specific embodiment

Following example is for further describing the present invention rather than restriction the present invention.

Experimental example 1. arteannuin, dihydroarteannuin, Artemether and artesunate suppress the amount-result relation that the CpG-ODN inducing cell factor discharges.

Cultivate mouse macrophage RAW264.7, adjusting concentration of cell suspension is 2 * 10 ⁶/ ml adds in 48 orifice plates, every hole 0.4ml.Put 37 ℃ of CO ₂Incubator makes cell attachment after cultivating 4h, the arteannuin (5,10,20,40,80 μ g/ml) of adding variable concentrations or dihydroarteannuin, Artemether, artesunate, the zest CpG ODN (5 '-TCC ATG ACG TTC CTG ACG TT-3 ') that adds 10 μ g/ml after 2 hours again, put and get cells and supernatant cytokine TNF-α to be measured after 37 ℃, CO2 incubator are cultivated 4h, after 4 hours, get cells and supernatant cytokine IL-6 to be measured.The concentration of TNF-α and IL-6 in the employing double-antibody sandwich elisa method mensuration cells and supernatant, clear and definite arteannuin or derivant suppress CpG ODN and induce RAW264.7 to discharge effect of cytokines.

Table 1 arteannuin, dihydroarteannuin, Artemether and artesunate suppress CpG ODN and induce the RAW264.7 cell to discharge dose-effect relationship (n=3, the x ± SD) of cytokine

^**p＜0.01 vs CpG ODN

This time experimental result shows that arteannuin significantly suppresses CpG ODN and induces RAW264.7 to discharge cytokine, increases with arteannuin concentration, and its inhibitory action strengthens (p＜0.01 sees Table 1); Dihydroarteannuin, Artemether and artesunate also induce RAW264.7 to discharge cytokine to CpG ODN also remarkable inhibitory action.

Experimental example 2. arteannuin, dihydroarteannuin, Artemether and artesunate suppress the amount-result relation that the hot colibacillus deactivating inducing cell factor discharges.

Cultivate mouse macrophage RAW264.7, adjusting concentration of cell suspension is 2 * 10 ⁶/ ml adds in 48 orifice plates, every hole 0.4ml.Put 37 ℃ of CO ₂Incubator makes cell attachment after cultivating 4h, adds the arteannuin (5,10,20,40,80 μ g/ml) of variable concentrations or dihydroarteannuin, Artemether or the artesunate of 40 μ g/ml, adds 1 * 10 again after 2 hours ⁶The hot colibacillus deactivating of/ml is put and is got cells and supernatant cytokine TNF-α to be measured after 37 ℃, CO2 incubator are cultivated 4h, gets cells and supernatant cytokine IL-6 to be measured after 4 hours.The concentration of TNF-α and IL-6 in the employing double-antibody sandwich elisa method mensuration cells and supernatant, clear and definite arteannuin or derivant suppress hot colibacillus deactivating and induce RAW264.7 to discharge effect of cytokines.

Table 2 arteannuin, dihydroarteannuin, Artemether and artesunate suppress hot colibacillus deactivating and induce the RAW264.7 cell to discharge dose-effect relationship (n=3, the x ± SD) of TNF-α

 

^**p＜0.01 vs E.coli

This time experimental result shows that arteannuin significantly suppresses hot colibacillus deactivating and induces RAW264.7 to discharge cytokine, increases with arteannuin concentration, and its inhibitory action strengthens (p＜0.01 sees Table 2); Dihydroarteannuin, Artemether and artesunate also induce RAW264.7 to discharge cytokine to hot colibacillus deactivating inhibitory action.。

Experimental example 3. arteannuin suppress the time-effect relationship that the CpG ODN inducing cell factor discharges.

Cultivate mouse macrophage RAW264.7, adjusting concentration of cell suspension is 2 * 10 ⁶/ ml adds in 48 orifice plates, every hole 0.4ml.Put 37 ℃, CO ₂Incubator makes cell attachment after cultivating 4h, to add the CpG ODN time is 0 o'clock point mutually, added 20 μ g/ml arteannuin respectively at-4 ,-2 ,-1,0,1,2 hours, put and get cells and supernatant TNF-α to be determined after 37 ℃, CO2 incubator are cultivated 4h, after 4 hours, get cells and supernatant cytokine IL-6 to be measured.Clear and definite arteannuin suppresses CpG ODN and induces RAW264.7 to discharge the ability of cytokine.

Table 3 arteannuin suppresses CpG ODN and induces RAW264.7 to discharge the time-effect relationship (x ± SD) of TNF-

^**p＜0.01 vs CpG

This time experimental result shows that arteannuin significantly suppresses CpG ODN and induces RAW264.7 to discharge cytokine, add arteannuin in advance and after adding CpG ODN, add arteannuin, all can suppress release of cytokines, but add inhibitory action stronger (p＜0.01 sees Table 3) in advance.

Experimental example 4. arteannuin suppress the time-effect relationship that the hot colibacillus deactivating inducing cell factor discharges.

Cultivate mouse macrophage RAW264.7, adjusting concentration of cell suspension is 2 * 10 ⁶/ ml adds in 48 orifice plates, every hole 0.4ml.Put 37 ℃ of CO ₂Incubator makes cell attachment after cultivating 4h, to add the hot colibacillus deactivating time is 0 o'clock point mutually, added 20 μ g/ml arteannuin respectively at-4 ,-2 ,-1,0,1,2 hours, put and get cells and supernatant TNF-α to be determined after 37 ℃, CO2 incubator are cultivated 4h, after 4 hours, get cells and supernatant cytokine IL-6 to be measured.Clear and definite arteannuin suppresses hot colibacillus deactivating and induces RAW264.7 to discharge the ability of cytokine.

Table 4 arteannuin suppresses hot colibacillus deactivating and induces RAW264.7 to discharge time-effect relationship (n=3, the x ± SD) of TNF-α

^**p＜0.01 vs E.coli

This time experimental result shows that arteannuin significantly suppresses hot colibacillus deactivating and induces RAW264.7 to discharge cytokine, give arteannuin after adding arteannuin in advance or adding hot colibacillus deactivating, all can suppress release of cytokines, but add arteannuin inhibitory action stronger (p＜0.01 sees Table 4) in advance.

Experimental example 5. arteannuin and derivant thereof are attacked the protective effect of mice to CpG-ODN.

Cleaning level 60 of the kind white mice in Kunming (Medical University Of Chongqing's Experimental Animal Center provides), body weight 18.6 ± 0.5g/ only, male and female half and half, be divided into matched group, arteannuin group (100mg/kg), CpG ODN at random and organize (4mg/kg), arteannuin (50,100,200mg/kg) or artemisinin derivative+CpG-ODN.Every group of 10 animals.Contain CpG ODN treated animal and gave D aminogalactose in 1 hour in advance.Contrast does not give any reagent; The arteannuin group gives the arteannuin of 200mg/kg, and administering mode is a gastric infusion; CpG ODN organizes, and gives the CpG ODN of 4mg/kg body weight, and administering mode is a tail vein injection; Arteannuin or derivatives thereof+CpG ODN group after the filling stomach gives the various dose arteannuin, gives the CpG ODN of 4mg/kg body weight immediately.Give normal diet and drinking-water after administration finishes, observe mice ordinary circumstance and mortality rate (table 5) in 7 days.

Table 5 arteannuin, dihydroarteannuin, Artemether and artesunate are attacked the protective effect of mice to CpG ODN

^*p＜0.05， ^**p＜0.01 vs CpG

This experiment shows that arteannuin, dihydroarteannuin and Artemether all can reduce CpG ODN and attack mortality of mice, shows that the mice that pro-inflammatory cytokine is attacked has protective effect.

Experimental example 6. arteannuin and derivant thereof are attacked the protective effect of mice to hot colibacillus deactivating.

Cleaning level 60 of the kind white mice in Kunming (Medical University Of Chongqing's Experimental Animal Center provides), body weight 19.9 ± 0.4g/ only, male and female half and half, be divided into matched group, arteannuin group, hot colibacillus deactivating group at random, arteannuin (50,100,200mg/kg) or derivant (40mg/kg)+hot colibacillus deactivating group.Every group of 10 animals.Contrast does not give any reagent; Arteannuin or derivant group are irritated stomach and are given arteannuin or derivant; Hot colibacillus deactivating group gives 1.1 * 10 ¹¹The hot colibacillus deactivating 35218 of/kg; Arteannuin or derivant+hot colibacillus deactivating group after the filling stomach gives arteannuin, gives hot colibacillus deactivating immediately.Give normal diet and drinking-water after administration finishes, observe mice ordinary circumstance and mortality rate (table 6) in 7 days.

Table 6 arteannuin is attacked the protective effect of mice to hot colibacillus deactivating

^*p＜0.05； ^**p＜0.01 vs E.coli

This experimental result shows: arteannuin and derivant all can reduce mortality of mice, and the mice that pro-inflammatory cytokine is attacked has protective effect.

The protective effect that experimental example 7. arteannuin and derivant thereof are attacked mice to escherichia coli 35218.

Cleaning level Kunming kind white mice (Medical University Of Chongqing's Experimental Animal Center provides), body weight 19.9 ± 0.5g/ only, male and female half and half are divided into matched group, arteannuin group, escherichia coli group at random, arteannuin (50,100,200mg/ml) or derivant+escherichia coli group.Contrast does not give any reagent; Arteannuin or derivant group are irritated arteannuin or the derivant that stomach gives 200mg/kg; The escherichia coli group gives 1.1 * 10 ⁵The escherichia coli that/kg lives; Arteannuin or derivant+escherichia coli group after the filling stomach gives arteannuin or derivant, gives escherichia coli immediately.Give normal diet and drinking-water after administration finishes, observe mice ordinary circumstance and mortality rate (table 7) in 7 days.

The protective effect that table 7 arteannuin is attacked mice to escherichia coli 35218

^*p＜0.5； ^**p＜0.01 vs E.coli

This experimental result shows: arteannuin and derivant thereof all can reduce mortality of mice, and the mice that pro-inflammatory cytokine is attacked has protective effect.

Experimental example 8. arteannuin and derivant thereof are attacked the protective effect of mice to hot deactivation staphylococcus aureus.

Cleaning level Kunming kind white mice (Medical University Of Chongqing's Experimental Animal Center provides), body weight 20.1 ± 0.4g/ only, male and female half and half, be divided into matched group, arteannuin group, escherichia coli group at random, arteannuin (50,100,200mg/kg) or derivant (40mg/kg)+hot deactivation staphylococcus aureus group.Contrast does not give any reagent; Arteannuin or derivant group are irritated the arteannuin that stomach gives 200mg/kg; Hot colibacillus deactivating group gives 1.1 * 10 ⁴The hot deactivation staphylococcus aureus of/kg; Arteannuin or derivant+hot deactivation staphylococcus aureus group after the filling stomach gives arteannuin or derivant, gives hot deactivation staphylococcus aureus immediately.Give normal diet and drinking-water after administration finishes, observe mice ordinary circumstance and mortality rate (table in 7 days.

Table 8 arteannuin and derivant thereof are attacked the protective effect of mice to staphylococcus aureus

^*p＜0.5； ^**p＜0.01 vs E.coli

This experimental result shows: arteannuin and derivant thereof all can reduce mortality of mice, and the mice that pro-inflammatory cytokine is attacked has protective effect.

Experimental example 9. arteannuin are attacked the influence of mice serum cytokine-expressing to CpG ODN, hot colibacillus deactivating

Cleaning level 48 of the kind white mice in Kunming (Medical University Of Chongqing's Experimental Animal Center provides), body weight 19.9 ± 0.5g/ only, male and female half and half, be divided into matched group, arteannuin group, CpG ODN group at random, arteannuin+CpG-ODN group, hot colibacillus deactivating group, arteannuin+hot colibacillus deactivating group, 10 of every treated animals.Contrast does not give any reagent.The arteannuin group gives the arteannuin of 200mg/kg, and administering mode is a gastric infusion; CpG ODN organizes, hot colibacillus deactivating group, gives the CpG ODN, 1.1 * 10 of 4mg/kg body weight respectively ¹¹The hot colibacillus deactivating group of/kg body weight, administering mode is tail vein injection; Arteannuin+CpG ODN group after the filling stomach gives arteannuin, gives CpG ODN, hot colibacillus deactivating group immediately.Plucking eyeball after administration finishes gets the centrifugal immediately indwelling supernatant of blood and is stored in-20 ℃, cytokine TNF-α to be determined (table 9).

Table 9 arteannuin reduces CpG ODN, hot colibacillus deactivating is attacked mice serum cytokine TNF-α (pg/ml) and expressed

^*p＜0.5 vs NO ART

This experimental result shows: arteannuin can significantly reduce CpG ODN, hot colibacillus deactivating is attacked the mice serum cytokine-expressing.

The pyemic clinical research that experimental example 10. arteannuin cause because of antibacterial in treatment

Selecting bacteria sepsis patient 50 examples, wherein 30 people organize as treatment, wherein male 19 examples, woman's 11 examples, age, average 38.6 ± 13.1 years old, treatment group all oral arteannuin on the basis of conventional therapy was treated in 19-70 year, the bacteria clearance of observing treatment group patient obviously improves, and sepsis obtains obvious control.Other 20 people only give conventional therapy, do not adopt arteannuin to treat.Effect criterion is according to effective, invalid 2 grades of evaluations, effectively: (1) sepsis symptom is controlled, and the state of an illness is clearly better; (2) serum TNF-α concentration significantly reduces.Invalid: (1) medication after 3 days the sepsis state of an illness do not have and take a turn for the better or increase the weight of; (2) serum TNF-α concentration concentration does not have remarkable reduction.Untoward reaction evaluation with patient in the medication process and the untoward reaction that occurs in the 5d after the medication and unusual result of laboratory test according to relevant with medicine, may be relevant, irrelevant, may have nothing to do, can't determine 5 grades and evaluate, relevant and may relevantly be listed as people's untoward reaction.

The arteannuin tablet of administrated method: 200mg is oral, 12 hours 1 time, the course of treatment 5-7d.

The pyemic effect of treatment after the medication is as shown in the table:

Table 1. prevention and treatment sepsis clinical observation situation

Group	n	Effectively	Invalid	Effective percentage
					Arteannuin treatment group	30	28	2	93
The conventional therapy group	20	15	5	75
					Add up to	50	43	7	86

Table 2. treatment group and matched group serum TNF-α concentration

Group	n	Significantly reduce	Do not have significantly and reduce	Effective percentage
					Arteannuin treatment group	30	29	1	97
The conventional therapy group	20	13	7	65
					Add up to	50	42	8	84

Untoward reaction: there are 2 routine patients mild nausea, dizziness etc. to occur, feed back transference cure, all the other do not have, and other is bad.

Can obtain conclusion from above experiment: arteannuin has reasonable curative effect in treatment aspect bacterial sepsis.

In like manner, the arteannuin tablet of oral 200mg is oral, and 12 hours 1 time, 5-7d can prevent or treat the sepsis that causes because of CpG ODN the course of treatment.

Same, dihydroartemisinine, Artemether, arteether, artesunate all can reach same pharmacological effect.

Embodiment 1

Get arteannuin 200 grams (purity 98%) of natural extract, lactose 50 grams, gelatinized corn starch is an amount of, magnesium stearate is an amount of, behind the mix homogeneously, is prepared into 1000 with direct compression process, packing can obtain the tablet that specification is 200mg then, and device therefor is the conventional equipment of this area.

Dihydroartemisinine, Artemether, arteether, artesunate all can be prepared into the tablet of 200mg specification with reference to embodiment 1.

Embodiment 2

Get arteannuin 100 grams (purity 98%) of natural extract, lactose 50 grams, gelatinized corn starch is an amount of, magnesium stearate is an amount of, behind the mix homogeneously, is prepared into 1000 with direct compression process, packing can obtain the tablet that specification is 100mg then, and device therefor is the conventional equipment of present production.

Dihydroartemisinine, Artemether, arteether, artesunate all can be prepared into the tablet of 100mg specification with reference to embodiment 2.

Embodiment 3

Get arteannuin 50 grams (purity 98%) of natural extract, lactose 50 grams, gelatinized corn starch is an amount of, magnesium stearate is an amount of, behind the mix homogeneously, is prepared into 1000 with direct compression process, packing can obtain the tablet that specification is 50mg then, and device therefor is the conventional equipment of present production.

Dihydroartemisinine, Artemether, arteether, artesunate all can be prepared into the tablet of 50mg specification with reference to embodiment 3.

Embodiment 4

Get arteannuin 200 grams (purity 98%) of natural extract, starch 30 grams, dextrin 5 grams, an amount of mix homogeneously of magnesium stearate, 1000 No. 1 capsules of packing into divide then and pack bottle into or be processed into box promptly.

Dihydroartemisinine, Artemether, arteether, artesunate all can be prepared into the capsule of 200mg with reference to embodiment 4.

Embodiment 5

Get arteannuin 200 grams 100 grams (purity 98%) of natural extract, starch 30 grams, dextrin 5 grams, an amount of mix homogeneously of magnesium stearate, 1000 No. 1 capsules of packing into divide then and pack bottle into or be processed into box promptly.

Dihydroartemisinine, Artemether, arteether, artesunate all can be prepared into the capsule of 100mg specification with reference to embodiment 5.

Embodiment 6

Get arteannuin 50 grams (purity 98%) of natural extract, starch 30 grams, dextrin 5 grams, an amount of mix homogeneously of magnesium stearate, 1000 No. 1 capsules of packing into divide then and pack bottle into or be processed into box promptly.

Dihydroartemisinine, Artemether, arteether, artesunate all can be prepared into the capsule of 50mg specification with reference to embodiment 6.

Embodiment 7

Get arteannuin 200 grams of natural extract, add water for injection and this area wetting agent commonly used such as tween 80, this area suspending agent such as methylcellulose commonly used, the content that makes wetting agent is every liter of 0.1-0.2% gram, the content that makes suspending agent is every liter of 0.5-1% gram, make with ultrasonic Treatment then and be uniformly dispersed, filter, transfer pH value, embedding, sterilization to obtain 1000 muddy outstanding agent.Device therefor is this area common apparatus.

In like manner, according to embodiment 7, can obtain the muddy outstanding agent of arteannuin of 100mg and 50mg specification.

Dihydroartemisinine, Artemether, arteether, artesunate all can be prepared into the muddy outstanding agent of 50mg, 100mg, 200mg specification with reference to embodiment 7.

 

 

1. dihydroartemisinine, the application of Artemether in the pyemic medicine of preparation prevention or treatment CpG ODN initiation.

2. dihydroartemisinine, the application of Artemether in the medication for treating pyemia of preparation prevention or treatment antibacterial and CpG ODN initiation.

3. according to claim 1 or 2 each described purposes, it is characterized in that dihydroartemisinine, Artemether are prepared into any preparation on the pharmaceutics in pharmacy procedure.