CN106074482A - The compositions of the derivant of Artalbic acid is used for preparing anti-chronic obstructive pulmonary disease - Google Patents
The compositions of the derivant of Artalbic acid is used for preparing anti-chronic obstructive pulmonary disease Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/12—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a ring other than a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/24—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/25—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
Abstract
The invention discloses the application in anti-chronic obstructive pulmonary disease of the compositions of O (bischloroethylamines base) ethyl of a kind of Artalbic acid and O (two (2 methylmercaptoethyl) amido) ethyl derivative, the present invention relates to organic synthesis and medicinal chemistry art, be specifically related to O (bischloroethylamines base) ethyl of Artalbic acid and O (two (2 methylmercaptoethyl) amido) compositions of ethyl derivative, preparation method and in the purposes prepared on anti-chronic obstructive pulmonary disease.The invention discloses O (bischloroethylamines base) ethyl of a kind of Artalbic acid and compositions of O (two (2 methylmercaptoethyl) amido) ethyl derivative and preparation method thereof.Pharmacological experiment shows, O (bischloroethylamines base) ethyl of the Artalbic acid of the present invention has the effect of anti-chronic obstructive pulmonary disease with the compositions of O (two (2 methylmercaptoethyl) amido) ethyl derivative, has the value developing anti-chronic obstructive pulmonary disease.
Description
Technical field
The present invention relates to organic synthesis and medicinal chemistry art, be specifically related to compositions, preparation method and its usage.
Background technology
Chronic obstructive pulmonary disease (chronic obstructive pulmonary disease, COPD) is a kind of complete
Chronic disease common in the range of ball, is number four in the cause of death of the whole world at present, predicts according to World Health Organization (WHO), to 2020
Year, COPD will be number five in global disease is fallen ill, and be number three in the cause of death.
COPD is the disease of a kind of not fully reversible flow limitation feature, with pulmonary to harmful gas or toxic granular
Abnormal inflammatory reaction is relevant, and its chronic inflammatory reaction is throughout air flue, pulmonary parenchyma and Pulmonary Vascular.The cell participating in COPD has neutral grain
The inflammatory cells such as cell, T lymphocyte and macrophage, discharge multiple inflammatory mediator, such as leukotriene B after cell is activated4
(LTB4), interleukin 8 (IL-8), RANTES, Eotaxin, tumor necrosis factor α (TNF α), GELB
(MMP-9) etc., the inflammatory reactions such as pulmonary parenchyma destruction, Pulmonary Vascular are participated in.Pathological change feature show as alveolar space inflammatory cell (as
Macrophage) infiltration, bronchia and peribronchiolar stove inflammatory cell infiltration, the expansion of lung tissue edge alveolar space, broken
Bad, alveolar wall broadens, its epithelial cell swelling, become round, partial exfoliation.COPD phase close with chronic bronchitis and emphysema
Closing, but definition is upper different, bronchial asthma is relevant with atopic allergy, and its flow limitation tool reversibility is (with chronic
It is not fully reversible that tracheitis there will be flow limitation when merging).There is no now medicine and can contain the Progressive symmetric erythrokeratodermia development of the COPD state of an illness,
The progress of its Drug therapy is relatively slow, and the medicine for the treatment of asthma usually is used for treating COPD by clinic at present, due to
The pathogenesis of COPD is different from asthma, it is difficult to obtain satisfied curative effect.
From natural product, find compound or lead compound and carry out structural modification and obtain its derivant, thus obtaining
The potential drug of high-efficiency low-toxicity most has important value.
The compound I that the present invention relates to be one within 2011, deliver (Antonella Maggio et al.,
2011.Artalbic acid,a sesquiterpene with an unusual skeleton from Artemisia
Alba (Asteraceae) from Sicily.Tetrahedron Letters, 52 (2011) 4,543 4545) compound, I
Compound I has been carried out structural modification, it is thus achieved that two new derivant i.e. compound III and compound IV, and use chemical combination
Thing III and compound IV is prepared for compositions and chronic obstructive pulmonary disease activity anti-to said composition is evaluated, and it has
Anti-chronic obstructive pulmonary disease activity.
Summary of the invention
The invention discloses a new compositions, said composition is made up of compound III and compound IV, said composition
The mass percent of middle compound III and compound IV is respectively 65% and 35%.
Compositions disclosed by the invention can make pharmaceutically acceptable salt or pharmaceutically acceptable carrier.
Long-term smoking is modal mankind's COPD paathogenic factor, and we simulate mice COPD mould at the induction of use for laboratory medicated cigarette
Type, intends the mitigation of the mice COPD that medicated cigarette is induced by the research present composition.
Present invention aim at providing present composition application in preparing anti-COPD disease medicament.The present invention combines
Thing is gastric infusion under dosage 10mg/kg, has the generation of inflammatory cytokine TNF α in the COPD mice BALF of medicated cigarette induction
Inhibitory action；Secretion to chemotactic factor RANTES has inhibitory action；Inflammatory cell in BALF raised inhibitory action.
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by concrete real
Execute any restriction of example, but be defined in the claims.
Detailed description of the invention
The preparation of embodiment 1 compound Artalbic acid
The document that the preparation method of compound Artalbic acid (I) is delivered with reference to Antonella Maggio et al.
(Antonella Maggio et al.,2011.Artalbic acid,a sesquiterpene with an unusual
skeleton from Artemisia alba(Asteraceae)from Sicily.Tetrahedron Letters,52
(2011) 4,543 4545) method.
The synthesis of O-bromoethyl derivant (II) of embodiment 2Artalbic acid
Compound I (266mg, 1.00mmol) is dissolved in 10mL benzene, in solution, adds tetrabutyl ammonium bromide (TBAB)
(0.08g), glycol dibromide (3.760g, 20.00mmol) and 50% sodium hydroxide solution of 6mL.Mixture is Celsius 40
Degree stirring 16h.After 16h, reactant liquor is poured in frozen water, be extracted twice with dichloromethane immediately, merge organic phase solution.So
Washing organic phase solution 5 times with water and saturated aqueous common salt successively afterwards, then be dried with anhydrous sodium sulfate, last concentrating under reduced pressure is removed
Solvent obtains product crude product.Product crude product silica gel column chromatography purification (flowing is mutually: petroleum ether/acetone=100:1.0, v/v),
Collect brown concentrate elution band and fling to solvent and i.e. obtain the brown ceramic powder (272mg, 73%) of compound II.
1H NMR(500MHz,DMSO-d6)δ11.41(s,1H),6.06(s,1H),5.76(s,1H),4.99(s,1H),
4.71(s,1H),4.56(s,1H),3.86(s,2H),3.54(s,2H),2.65(s,1H),2.43(s,2H),2.33(s,2H),
2.10(s,1H),1.64(s,3H),1.54(s,1H),1.44(s,2H),0.95(s,3H).
13C NMR(125MHz,DMSO-d6)δ201.95(s),175.93(s),149.13(s),148.15(s),117.05
(s),109.43(s),81.86(s),70.27(s),57.68(s),41.26(s),39.07(s),38.86(s),35.69(s),
33.36(s),30.72(s),20.44(s),18.42(s).
HRMS(ESI)m/z[M+H]+calcd for C17H26BrO4:373.1014；found 373.1017.
The synthesis of the O-(bischloroethylamines base) ethyl derivative (III) of embodiment 3Artalbic acid
1, the synthesis of O-(two hydroxyethylamines) ethyl derivative of Artalbic acid
Compound II (187mg, 0.5mmol) is dissolved in the middle of 20mL acetonitrile, be added thereto to Anhydrous potassium carbonate (690mg,
5.0mmol), potassium iodide (252mg, 1.5mmol) and diethanolamine (1051mg, 10mmol), mixture is heated to reflux 1h.Reaction
Reactant liquor is poured in 20mL frozen water after end, extract 3 times with equivalent dichloromethane, merge organic facies.Successively with water and saturated
Organic facies after brine It merging, then be dried with anhydrous sodium sulfate, concentrating under reduced pressure is removed solvent and is obtained product crude product.Produce
Thing crude product silica gel column chromatography purification (flowing is mutually: petroleum ether/acetone=100:1.0, v/v), collects yellow and concentrates elution band
And fling to the faint yellow solid that solvent i.e. obtains O-(two hydroxyethylamines) ethyl derivative of compound Artalbic acid
(146.9mg, 74%).
1H NMR(500MHz,DMSO-d6)δ18.72(s,1H),δ6.11(s,1H),5.80(s,1H),5.14(s,1H),
4.73 (s, 1H), 4.63 (s, 1H), 3.57 (s, 2H), 3.45 (s, 4H), 2.70 (d, J=15.6Hz, 3H), 2.60 (s, 4H),
2.50 (s, 2H), 2.46 (s, 2H), 2.33 (s, 1H), 1.88 (s, 2H), 1.68 (s, 3H), 1.62 (d, J=19.9Hz, 3H),
1.02(s,3H).
13C NMR(125MHz,DMSO-d6)δ202.01(s),176.11(s),149.21(s),148.55(s),117.15
(s),109.60(s),81.93(s),67.25(s),59.28(s),57.88(s),56.83(s),53.74(s),41.36(s),
39.24(s),38.93(s),35.88(s),30.82(s),20.61(s),18.49(s).
HRMS(ESI):m/z[M+H]+calcd for C21H36N1O6:398.2543；found:398.2547.
O-(two hydroxyethylamines) ethyl derivative of Artalbic acid
2, the synthesis of the O-(bischloroethylamines base) ethyl derivative (III) of Artalbic acid
Synthesize O-(two hydroxyethylamines) ethyl derivative of abundant Artalbic acid, by Artalbic acid's
O-(two hydroxyethylamines) ethyl derivative (0.100g, 0.5mmol) is dissolved in 4mL chloroform, be added dropwise over thionyl chloride (0.238g,
2mmol), reactant is heated to reflux 2h.Reactant is cooled to room temperature, the thionyl chloride of dropping Methanol Decomposition excess, reduces pressure dense
Contracting removes solvent.Product, through silica gel column chromatography purification (petroleum ether/acetone 100:0.2, v/v), obtains the faint yellow of compound III
Solid (145.4mg, 67%).
1H NMR(500MHz,DMSO-d6)δ13.05(s,1H),δ6.05(s,1H),5.75(s,1H),4.67(s,2H),
(4.58 d, J=7.5Hz, 1H), 3.68 (s, 4H), 3.50 (s, 2H), 2.86 (s, 2H), 2.74 (s, 2H), 2.62 (d, J=
0.9Hz,3H),2.44(s,2H),2.38(s,2H),2.22(s,1H),1.61(s,3H),1.49(s,1H),1.42(s,2H),
0.95(s,3H).
13C NMR(125MHz,DMSO-d6)δ201.68(s),175.56(s),148.88(s),147.80(s),116.82
(s),109.05(s),81.60(s),66.70(s),57.44(s),55.79(s),53.30(s),41.03(s),39.21(s),
38.80(s),38.49(s),35.44(s),30.38(s),20.17(s),18.05(s).
HRMS(ESI):m/z[M+H]+calcd for C21H34Cl2NO4 +:434.1865；found:434.1861.
The synthesis of O-(two (2-methylmercaptoethyl) amido) ethyl derivative (III) of embodiment 4Artalbic acid
Prepare abundant compound III, compound III (0.217g, 0.5mmol) is dissolved in 10mL ethanol, under room temperature
Adding sodium methyl mercaptide (0.21g, 3mmol), reactant is heated to reflux 2h.Concentrating under reduced pressure removes solvent, products therefrom silicagel column
Chromatography is purified (petroleum ether/acetone 100:0.3, v/v), obtains yellow solid, i.e. compound IV (0.158g, 69%).
1H NMR(500MHz,Chloroform-d1)δ18.86(s,1H),6.14(s,1H),5.82(s,1H),5.33
(s, 1H), 4.75 (s, 1H), 4.62 (s, 1H), 3.54 (s, 2H), 2.86 (s, 1H), 2.72 (dd, J=18.2,6.8Hz,
11H),2.50(s,2H),2.39(s,2H),2.12(s,6H),1.71(s,3H),1.56(s,2H),1.41(s,1H),1.06
(s,3H).
13C NMR(125MHz,DMSO-d6)δ201.96(s),175.97(s),149.17(s),148.22(s),117.11
(s),109.47(s),81.85(s),67.07(s),57.69(s),53.56(s),52.49(s),41.29(s),39.00(s),
38.79(s),35.63(s),32.15(s),30.74(s),20.43(s),18.43(s),14.87(s).
HRMS(ESI):m/z[M+H]+calcd for C23H40NO4S2 +:434.1865；found:434.1863.
The anti-chronic obstructive pulmonary disease of embodiment 5 compositions is tested
Method: SPF level female BAl BIc/c mice, 18-20g, is randomly divided at Normal group, model control group, medicine
Reason group (compositions, compound III and compound IV 10mg/kg, gastric infusion), often group 10.Mice is placed in 4L container
In, sootiness every day (the Nanjing red shell of board medicated cigarette, tar content be less than 16mg), five times one week, continuous surrounding, before sootiness every day 1
Hour gastric infusion, mice after last sootiness 1 hour, anaesthetize with sodium phenobarbital, with the PBS of 0.6mL pre-cooling
(pH7.0) lung perfusion, rinses 3 times, sucking-off bronchoalveolar lavage fluid (BALF), and 250 × g is centrifuged 10min, and supernatant is for dividing
Analysis TNF α, the content of RANTES.Cell PBS is resuspended, counting, with Rui Shi-Giemsa staining after cell smear, analyzes
The change of inflammatory cell in BALF.
The preparation of compositions: the powder that will cross the 65mg compound III of 200 mesh nets after grinding crosses 200 after grinding
The powder of the 35mg compound IV of mesh net loads in tubule with cover and i.e. obtains 100mg compositions with the mixing of turbine stirring instrument,
Obtain the solution of compositions by the compositions of this 100mg of water dissolution during use.
Experimental example 1 compositions generates inhibitory action to inflammatory mediator in COPD mouse bronchial bronchoalveolar lavage fluid (BALF)
(1) compositions generates inhibitory action to TNF α in COPD mice BALF
Pro-inflammatory cytokines TNF α is the startup factor in the pathogenic process of COPD.The TNF α level of COPD patient is higher than
Normal person, the bronchial epithelial cell of cultivation contacts with the smog of medicated cigarette can TNF secretion α.TNF α can promote neutrophilic granulocyte to take off
Granule, induction is played mucomembranous cell hypertrophy and hypersecretion, is increased epithelial cell IL-8 and generate, increase macrophage matrix metal egg
White enzyme generates, and promotes airway hyperreactivity.This experiment purpose is what TNF α in COPD mice BALF was generated by study group's compound
Impact, the results are shown in Table 1.
The impact that TNF α in COPD mice BALF is generated by table 1 compositions
Note: * P < 0.05, compared with model control group；#P < 0.05, compared with Normal group.N=10.
Result: compositions to COPD model mice gastric infusion, can significantly reduce TNF α in mice BALF under 10mg/kg
Generation, and compound III and compound IV without this act on.
(2) compositions is to RANTES secretion inhibition in COPD mice BALF
The migration of inflammatory cell is regulated by chemotactic factor, and it is little that various Constituent cell core inflammatory cells all can secrete these
Molecule protein, in COPD pathogenic process, RANTES secretion increases, chemotactic Monocytes/Macrophages, T lymphocyte, oxyphil cell.
This experiment purpose is that study group's compound, on the impact of RANTES secretion in COPD mice BALF, the results are shown in Table 2.
Table 2 compositions is on the impact of RANTES secretion in COPD mice BALF
Note: * P < 0.05, compared with model control group；#P < 0.01, compared with Normal group.N=10.
Result: compositions under 10mg/kg to COPD model mice gastric infusion, it is possible to decrease RANTES in mice BALF
Secretion, and compound III and compound IV acts on without this.
Experimental example 2 compositions is to the inhibitory action of inflammatory cell recruitment in COPD mice BALF
(1) compositions is to the inhibitory action of neutrophil recruitment in COPD mice BALF
Neutrophilic granulocyte has important function in COPD falls ill, and it can discharge two kinds of serine proteases, elastic egg
White enzyme and cysteinyl proteinase-3, induced animal produces the pathological change of mankind's emphysema sample.Neutrophilic granulocyte life is of short duration,
The process that air flue and crossing gap chamber are recruited in its circulation is the rapidest.Pathological study proves some COPD patient bronchus group
Knit interior neutrophil numbers and increase relevant with the degree of airflow obstruction.Neutrophil numbers in the COPD patient air flue of smoking
Increasing, particularly those are with the patient of chronic bronchitis.Affect neutrophil recruitment in COPD patient lung main because of
Element strengthens for IL-8 chemotactic activity.This experiment purpose is that study group's compound is to neutrophil recruitment in COPD mice BALF
Impact, the results are shown in Table 3.
Table 3 compositions is on the impact of neutrophil recruitment in COPD mice BALF
Note: * P < 0.05；#P < 0.01, compared with Normal group.N=10.
Result: compositions under 10mg/kg to COPD model mice gastric infusion, it is possible to decrease in mice BALF, neutral grain is thin
Born of the same parents raise, and compound III and compound IV acts on without this.
(2) compositions is to the inhibitory action of macrophage recruitment in COPD mice BALF
In smoker and COPD patient lung, macrophage compared with normal crowd's level increases, and is gathered in alveolar, bronchioles more
And small airway.The small airway disease degree of alveolar wall macrophage numbers and light moderate emphysema and COPD patient is positive
Close.Lesion tissue COPD visible with damage location is slowly in progress to be increased parallel for a long time with chronic disease with macrophage.Huge bite
Cell may cause Elastic tissue degradation capability extremely to increase by release matrix metalloproteases, induces emophysematous generation.
This experiment purpose is that study group's compound, on the impact of macrophage recruitment in COPD mice BALF, the results are shown in Table 4.
Table 4 compositions is on the impact of macrophage recruitment in COPD mice BALF
Note: * P < 0.05, compared with model control group；#P < 0.01, compared with Normal group.N=10.
Result: compositions to COPD model mice gastric infusion, can significantly reduce huge in mice BALF biting under 10mg/kg
Raising of cell, and compound III and compound IV is without this remarkable effect.
Conclusion: compositions is gastric infusion under 10mg/kg, during the murine chronic obstructive pulmonary disease to medicated cigarette induction
The generation of inflammatory mediator and the secretion of chemotactic factor significantly inhibit effect, are impregnated with inflammatory cell significantly suppressing, right
Chronic obstructive pulmonary disease has significant therapeutic effect.And compound III and compound IV gastric infusion under 10mg/kg, to perfume (or spice)
Cigarette induction murine chronic obstructive pulmonary disease during the generation of inflammatory mediator and the secretion of chemotactic factor without significantly inhibiting work
With, to the infiltration of inflammatory cell without significantly inhibiting, to chronic obstructive pulmonary disease without any therapeutical effect.
The preparation of embodiment 6 composition tablet involved in the present invention
Taking 2 grams of compositionss, the customary adjuvant 18 grams of tablet is prepared in addition, and mixing, conventional tablet presses makes 100.
The preparation of embodiment 7 composition capsule involved in the present invention
Taking 2 grams of compositionss, the customary adjuvant such as starch 18 grams of capsule is prepared in addition, mixing, encapsulated makes 100.
Claims (10)
1. a compositions, is characterized by that said composition is made up of compound III and compound IV, compound in said composition
The mass percent of III and compound IV is respectively 65% and 35%,
2. the preparation method of compositions as claimed in claim 1, is characterized by: by powder and the compound IV of compound III
Powder be sufficiently mixed according to mass percent respectively 65% and 35%.
3. a compositions as claimed in claim 1 application in treatment chronic obstructive pulmonary disease.
4. the compositions as claimed in claim 3 application in treatment chronic obstructive pulmonary disease, is characterized by: described slowly
Property obstructive pulmonary disease is caused by smoking.
5. the compositions as claimed in claim 3 application in treatment chronic obstructive pulmonary disease, is characterized by: described group
The release of inflammatory mediator during compound suppression chronic obstructive pulmonary disease.
6. the compositions as claimed in claim 5 application in treatment chronic obstructive pulmonary disease, is characterized by: described inflammation
Property medium is TNF α.
7. the compositions as claimed in claim 3 application in treatment chronic obstructive pulmonary disease, is characterized by: described group
The secretion of chemotactic factor during compound suppression chronic obstructive pulmonary disease.
8. the compositions as claimed in claim 7 application in treatment chronic obstructive pulmonary disease, is characterized by: described in become
The change factor is RANTES.
9. the compositions as claimed in claim 3 application in treatment chronic obstructive pulmonary disease, is characterized by: described group
Raising of compound suppression inflammatory cell.
10. the compositions as claimed in claim 9 application in treatment chronic obstructive pulmonary disease, is characterized by: described
Inflammatory cell is neutrophilic granulocyte or macrophage.
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|---|---|---|---|
| CN201610473796.1A CN106074482A (en) | 2016-06-24 | 2016-06-24 | The compositions of the derivant of Artalbic acid is used for preparing anti-chronic obstructive pulmonary disease |
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| CN201610473796.1A CN106074482A (en) | 2016-06-24 | 2016-06-24 | The compositions of the derivant of Artalbic acid is used for preparing anti-chronic obstructive pulmonary disease |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102481282A (en) * | 2009-03-24 | 2012-05-30 | 新加坡国立大学 | Use of artemisinin derivatives for treatment of asthma and chronic obstructive pulmonary disease (copd) |
-
2016
- 2016-06-24 CN CN201610473796.1A patent/CN106074482A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102481282A (en) * | 2009-03-24 | 2012-05-30 | 新加坡国立大学 | Use of artemisinin derivatives for treatment of asthma and chronic obstructive pulmonary disease (copd) |
Non-Patent Citations (1)
| Title |
|---|
| ANTONELLA MAGGIO等: "Artalbic acid，a sesquiterpene with an unusual skeleton from Artemisia alba (Asteraceae) from Sicily", 《TETRAHEDRON LETTERS》 * |
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