CN106074526A - The composition of Schiglautone A derivative is used for preparing anti-rhinitis medicament thing - Google Patents
The composition of Schiglautone A derivative is used for preparing anti-rhinitis medicament thing Download PDFInfo
- Publication number
- CN106074526A CN106074526A CN201610416173.0A CN201610416173A CN106074526A CN 106074526 A CN106074526 A CN 106074526A CN 201610416173 A CN201610416173 A CN 201610416173A CN 106074526 A CN106074526 A CN 106074526A
- Authority
- CN
- China
- Prior art keywords
- composition
- rhinitis
- compound
- application
- medicament thing
- 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.)
- Pending
Links
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to organic synthesis and medicinal chemistry art, be specifically related to composition and in the purposes prepared on anti-rhinitis medicament thing.The invention discloses a kind of composition and preparation method thereof.Pharmacological experiment shows, the composition of the present invention has anti-rhinitis effect, has the value of exploitation anti-rhinitis medicament thing.
Description
Technical field
The present invention relates to organic synthesis and medicinal chemistry art, be specifically related to composition, preparation method and its usage.
Background technology
Rhinitis is common clinical and frequently-occurring disease, and the generation of rhinitis is mainly relevant with allergic reaction, belongs to immune inflammation
Category.At present, treat rhinitis and mainly use the antihistamine drug such as teldane or the antiallergic such as tranilast, Ketotifen
Thing, these medicines are poor or invalid to chronicity and the recurrent exerbation curative effect of rhinitis.Therefore, definite ingredients, quality controllable and peace
Complete efficient micromolecular compound, in terms of developing treatment of rhinitis medicine, has potential value.
Find compound or lead compound and carry out structural modification and obtain its derivative from natural products, thus obtaining
The potential drug of high-efficiency low-toxicity has important value most.
The compound I that the present invention relates to be one within 2011, deliver (Fan-Yu Meng et al.,
2011.Schiglautone A,a New Tricyclic Triterpenoid with a Unique 6/7/9-Fused
Skeleton from the Stems of Schisandra glaucescens.Organic Letters 13(2011)
1502 1505) compound, we have carried out structural modification to compound I, it is thus achieved that two i.e. compounds of new derivative
III and compound IV, and it is prepared for composition with compound III and compound IV, and said composition anti-rhinitis activity is carried out
Evaluating, it has anti-rhinitis activity.
Content of the invention
The invention discloses a new composition, 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 45% and 55%.
Composition disclosed by the invention can make pharmaceutically acceptable salt or pharmaceutically acceptable carrier.
Pharmacodynamic experiment shows, the composition of the present invention has preferable anti-rhinitis effect.The present invention pharmaceutically can connect
The salt being subject to has same drug effect.
Composition 10mg/kg oral administration, nose that rat caused by antigen (ovalbumin) and histamine is scratched, sneeze anti-
Answer and nasal cavity vasopermeability raises inhibited, therefore, can be used for the medicine of preparation treatment rhinitis.
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by specifically
Any restriction of embodiment, but be defined in the claims.
Detailed description of the invention
The preparation of embodiment 1 compound Schiglautone A
Document (the Fan-Yu that the preparation method of compound Schiglautone A (I) is delivered with reference to Fan-Yu Meng et al.
Meng et al.,2011.Schiglautone A,a New Tricyclic Triterpenoid with a Unique 6/
7/9-Fused Skeleton from the Stems of Schisandra glaucescens.Organic Letters
13 (2011) 1,502 1505) method.
The synthesis of O-bromoethyl derivative (II) of embodiment 2 Schiglautone A
Compound I (502mg, 1.00mmol) is dissolved in 15mL benzene, in solution, adds TBAB (TBAB)
(0.08g), 1,2-Bromofume (7.520g, 40.00mmol) and 50% sodium hydroxide solution of 6mL.Mixture is Celsius 35
Degree stirring 8h.After 8h, reactant liquor is poured in frozen water, be extracted twice with dichloromethane immediately, merge organic phase solution.Then
Washing organic phase solution 3 times with water and saturated aqueous common salt successively, then being dried with anhydrous sodium sulfate, last reduced pressure concentration is removed molten
Agent obtains product crude product.Product crude product silica gel column chromatography purifies (flowing is mutually: petroleum ether/acetone=100:1.0, v/v), receives
Collection brown is concentrated elution band and flings to the brown ceramic powder (508mg, 71%) that solvent i.e. obtains compound II.
1H NMR(500MHz,DMSO-d6)δ13.40(s,1H),6.10(s,1H),5.63(s,1H),5.53(s,1H),
3.85 (d, J=11.2Hz, 4H), 3.52 (d, J=10.8Hz, 4H), 2.96 (s, 1H), 2.20 (s, 1H), 2.16 (s, 2H),
2.00 (s, 1H), 1.84 (d, J=13.9Hz, 4H), 1.69 (s, 1H), 1.58 (dd, J=22.2,8.5Hz, 4H), 1.51 (s,
1H), 1.47 (s, 1H), 1.26 (dd, J=9.1,4.4Hz, 4H), 1.21 (s, 1H), 1.08 0.98 (m, 4H), 0.96-0.94
(m,9H),0.94-0.85(m,6H).
13C NMR(125MHz,DMSO-d6)δ211.46(s),209.14(s),170.06(s),161.12(s),143.51
(s),132.01(s),127.77(s),85.96(s),82.40(s),70.19(s),69.10(s),57.14(s),52.73
(s),51.90(s),45.77(s),40.67(s),38.57(s),38.32(s),35.04(s),33.55(s), 33.27(s),
29.85(s),28.98(s),26.71(s),25.50(s),24.05(s),22.31(s),21.06(s),20.56(s),20.00
(s),18.69(s),18.11(s),15.07(s).
HRMS(ESI)m/z[M-H]-calcd for C34H51Br2O6:715.2032；found 715.2027.
The synthesis of O-(the 1H-tetrazole base) ethyl derivative (III) of embodiment 3 Schiglautone A
Be dissolved in compound II (358mg, 0.5mmol) in the middle of 15mL acetonitrile, be added thereto to Anhydrous potassium carbonate (345mg,
2.5mmol), KI (84mg, 0.5mmol) and 1H-tetrazole (1401mg, 20mmol), mixture is heated to reflux 5h.Reaction
Reactant liquor is poured in 20mL frozen water after end, extract three times with equivalent dichloromethane, merge organic phase.Use water and saturated successively
Organic phase after brine It merging, then be dried with anhydrous sodium sulfate, reduced pressure concentration is removed solvent and is obtained product crude product.Cause
For tautomerization, 1H-tetrazole base and two kinds of substitution products of 2H-tetrazole base can be generated at reaction conditions.Product is thick
Product silica gel column chromatography purifies (flowing is mutually: petroleum ether/acetone=100:1, v/v), collects faint yellow concentration elution band, then will
Faint yellow elution band concentrates, and is purified (flowing is mutually: petroleum ether/acetone=100:0.5, v/v) by silica gel column chromatography, collects successively
Two flaxen elution bands, concentrate front 1 elution band and i.e. obtain the faint yellow solid (79.8mg, 23%) of compound III.
1H NMR(500MHz,DMSO-d6)δ16.29(s,1H),9.99(s,1H),9.93(s,1H),6.25(s,1H),
5.76 (s, 1H), 5.40 (s, 1H), 4.57 (s, 1H), 4.38 (s, 1H), 4.32 (s, 1H), 4.21 (s, 1H), 3.96 (d, J=
11.9Hz,4H),3.33(s,1H),2.55(s,1H),2.51(s,2H),2.39(s,1H),1.98(s,3H),1.82–1.76
(m, 3H), 1.73 (s, 1H), 1.65 (d, J=6.5Hz, 2H), 1.60 (s, 1H), 1.53 (s, 1H), 1.47 1.37 (m, 4H),
1.30 (s, 1H), 1.19 (s, 1H), 1.10 (t, J=12.5Hz, 3H), 1.08 (t, J=12.5Hz, 9H), 1.03 (s, 3H),
0.86(s,3H).
13C NMR(125MHz,DMSO-d6)δ211.72(s),209.42(s),170.36(s),161.38(s),145.37
(s),143.80(s),132.29(s),128.04(s),86.25(s),82.68(s),66.14(s),65.60(s), 57.33
(s),52.91(s),52.08(s),46.81(s),45.95(s),40.84(s),38.76(s),38.50(s),35.21(s),
33.74(s),30.01(s),29.16(s),26.91(s),25.66(s),24.23(s),22.51(s),21.22(s),20.74
(s),20.20(s),18.85(s),18.29(s),15.27(s).
HRMS(ESI):m/z[M+H]+calcd for C36H55N8O6:695.4245；found:695.4248.
The synthesis of O-(benzimidazolyl) ethyl derivative of embodiment 4 Schiglautone A
Be dissolved in compound II (358mg, 0.5mmol) in the middle of 15mL acetonitrile, be added thereto to Anhydrous potassium carbonate (345mg,
2.5mmol), KI (84mg, 0.5mmol) and benzimidazole (1180mg, 10mmol), mixture is heated to reflux 6h.Reaction
After end pour reactant liquor in frozen water into, extract three times with equivalent dichloromethane, merge organic phase.Use water and saturated common salt successively
Organic phase after water washing merging, then be dried with anhydrous sodium sulfate, reduced pressure concentration is removed solvent and is obtained product crude product.Product is thick
Product silica gel column chromatography purifies (flowing is mutually: petroleum ether/acetone=100:1.5, v/v), collects brown and concentrates elution band, concentrates
I.e. obtain the brown solid (169.9mg, 43%) of compound IV.
1H NMR (500MHz, DMSO-d6) δ 13.32 (s, 1H), 8.38 (s, 2H), 7.66 (d, J=25.0Hz, 4H),
7.39 (s, 2H), 7.32 (s, 2H), 6.25 (s, 1H), 5.64 (d, J=18.7Hz, 2H), 4.34 (s, 1H), 4.28 (s, 1H),
4.18 (d, J=13.7Hz, 2H), 4.04 (s, 2H), 3.99 (s, 2H), 3.13 (s, 1H), 2.65 (s, 2H), 2.26 (s, 1H),
2.17 (s, 1H), 2.06 (s, 1H), 1.98 (s, 3H), 1.87 (d, J=16.4Hz, 2H), 1.66 (dd, J=8.0,6.6Hz,
4H), 1.62 (s, 1H), 1.49 (s, 1H), 1.41 (dd, J=19.6,10.4Hz, 2H), 1.37 (d, 2H), 1.20 1.11 (m,
4H), 1.07 (d, J=20.0Hz, 6H), 103 (d, J=20.0Hz, 3H), 1.01 (d, J=20.0Hz, 3H), 0.95 (d, J=
20.0Hz,3H).
13C NMR(125MHz,DMSO-d6)δ211.30(s),208.98(s),169.90(s),160.96(s),146.28
(s),143.34(s),139.64(s),133.48(s),131.85(s),127.61(s),123.92(s),123.35(s),
118.55(s),110.85(s),85.79(s),82.26(s),67.74(s),67.20(s),57.00(s),52.56(s),
51.73(s),45.63(s),44.94(s),40.49(s),38.42(s),38.17(s),34.86(s),33.40(s),29.68
(s),28.81(s),26.57(s),25.33(s),23.88(s),22.17(s),20.89(s),20.39(s),19.86(s),
18.52(s),17.87(s),14.93(s).
HRMS(ESI):m/z[M+H]+calcd for C48H63N4O6:791.4748；found:791.4744.
Embodiment 5 present composition causes the impact of rat allergic rhinitis to ovalbumin
Male SD rat, body weight 180～220g, lumbar injection ovalbumin 1mg and gel aluminum hydroxide 10mg, thereafter every
Day injection 1 time, totally 7 times.Began from the 14th day, in the nasal cavity of rat both sides, instill 1mg/ml ovalbumin normal saline solution every day
10ul, totally 7 times.In last is observed 30 minutes after instiling at once, rat is sneezed and wipes the number of times of nose, and trial drug is in white of an egg egg
White last instils and is orally administered to for first 1 hour.
The preparation of composition: the powder of the 45mg compound III that will cross 200 mesh nets after grinding crosses 200 after grinding
The powder of the 55mg compound IV of mesh net loads in tubule with cover and i.e. obtains 100mg composition with the mixing of turbine stirring instrument,
Dissolve, with water, the solution that the composition of this 100mg obtains composition during use.
From table 1, the sneeze of allergic rhinitis rat and scratching caused by composition (10mg/kg) substantially suppression ovalbumin
Grab nose reaction.Compound III and compound IV acts on without this.
Table 1 present composition causes the impact of rat allergic rhinitis to ovalbumin
* p < 0.05, compares with control group
The impact of the rat rhinitis that histamine is caused by embodiment 6 present composition
Male SD rat, body weight 180～220g, it is orally administered to after trial drug 1 hour, in the nasal cavity of both sides, instill 1M histamine
Normal saline solution 10ul, in observing 30 minutes, rat is sneezed and wipes the number of times of nose.
From table 2, the present composition (10mg/kg) significantly reduces the sneeze number of times of rhinitis rat caused by histamine, right
Nose of scratching reacts in suppression trend.Compound III and compound IV acts on without this.
Table 2 present composition causes the impact of rat rhinitis to histamine
P < 0.05, compares with control group
Embodiment 7 present composition causes the impact that rat nasal cavity vasopermeability raises to ovalbumin, histamine
Male SD rat, body weight 180～220g, observes ovalbumin and group with active sensitization rat and normal rat respectively
Nasal cavity vasopermeability that amine causes raises, and the method for sensitization of rat is tested with allergic rhinitis, after initial immunity the 14th day,
This, from tracheae to nasal intubation after anesthesia, is intubated and constant flow pump phase after fixing by rats by intraperitoneal injection yellow Jackets 40mg/kg
Even (0.25ml/min0, with 37 DEG C of normal saline flushing nasal cavities 10 minutes, the blue physiology of the 1%Evans of rat tail vein injection thereafter
Saline solution 5ml/kg, collected perfusate 10 minutes after 3 minutes.At sensitized rats and normal rat, perfusate contains ovum respectively
Albumin 1mg/ml and histamine 40ug/ml, the perfusate collected from nasal cavity centrifuges 10 minutes through 1200 × g, and at 620nm, colorimetric is surveyed
Determine the blue concentration of the Evans in supernatant, test medicine and antigen or first 1 hour oral administration of histamine perfusion.
From table 3, the nose of allergic rhinitis rat caused by the present composition (10mg/kg) substantially suppression ovalbumin
Chamber vasopermeability.Compound III and compound IV acts on without this.
Table 3 present composition causes the impact that rat nasal cavity vasopermeability raises to ovalbumin
* p < 0.01, compares with control group
From table 4, present composition 10mg/kg substantially reduces the nasal cavity vasopermeability of rat caused by histamine.Change
Compound III and compound IV acts on without this.
Table 4 present composition causes the impact that rat nasal cavity blood flow permeability raises to histamine
* p < 0.01, compares with control group
Conclusion: composition oral is administered, scratch rat caused by antigen (ovalbumin) and histamine nose, reaction of sneezing
And nasal cavity vasopermeability raises and has the effect of significantly inhibiting, therefore, can be used for the medicine of preparation treatment rhinitis.Compound III
Rat caused by antigen (ovalbumin) and histamine scratched nose, sneeze reaction and nasal cavity vasopermeability liter with compound IV
Height does not significantly inhibit effect, therefore, is not useable for the medicine of preparation treatment rhinitis.
The preparation of embodiment 8 composition tablet involved in the present invention
Taking 2 grams of compositions, the customary adjuvant 18 grams of tablet is prepared in addition, mixes, and conventional tablet presses makes 100.
The preparation of embodiment 9 composition capsule involved in the present invention
Taking 2 grams of compositions, the customary adjuvant such as starch 18 grams of capsule is prepared in addition, mixes, encapsulated makes 100.
Claims (10)
1. a composition, 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 45% and 55%,
2. the preparation method of composition as claimed in claim 1, is characterized by: by powder and the compound IV of compound III
Powder be respectively 45% and 55% according to mass percent and be sufficiently mixed.
3. a composition as claimed in claim 1 application in anti-rhinitis medicament thing.
4. application in anti-rhinitis medicament thing for the composition according to claim 3, is characterized by: described rhinitis is antigen institute
The rhinitis causing.
5. application in anti-rhinitis medicament thing for the composition according to claim 4, is characterized by: described antigen is white of an egg egg
In vain.
6. application in anti-rhinitis medicament thing for the composition according to claim 5, is characterized by: described composition can press down
Scratch caused by ovalbumin processed nose number of times and reaction of sneezing.
7. application in anti-rhinitis medicament thing for the composition according to claim 5, is characterized by: described composition can press down
The rising of nasal cavity vasopermeability caused by ovalbumin processed.
8. application in anti-rhinitis medicament thing for the composition according to claim 3, is characterized by: described rhinitis is histamine institute
The rhinitis causing.
9. application in anti-rhinitis medicament thing for the composition according to claim 8, is characterized by: described composition can press down
Scratch caused by histamine processed nose number of times and reaction of sneezing.
10. application in anti-rhinitis medicament thing for the composition according to claim 8, is characterized by: described composition is permissible
The rising of nasal cavity vasopermeability caused by suppression histamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610416173.0A CN106074526A (en) | 2016-06-13 | 2016-06-13 | The composition of Schiglautone A derivative is used for preparing anti-rhinitis medicament thing |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610416173.0A CN106074526A (en) | 2016-06-13 | 2016-06-13 | The composition of Schiglautone A derivative is used for preparing anti-rhinitis medicament thing |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106074526A true CN106074526A (en) | 2016-11-09 |
Family
ID=57845185
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610416173.0A Pending CN106074526A (en) | 2016-06-13 | 2016-06-13 | The composition of Schiglautone A derivative is used for preparing anti-rhinitis medicament thing |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106074526A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104814967A (en) * | 2015-04-15 | 2015-08-05 | 南京广康协生物医药技术有限公司 | Application of cleistanthus sumatranus ketone O-(1H-tetrazole base) ethyl ramification to preparing rhinitis-resisting medicine |
| CN104825468A (en) * | 2015-04-29 | 2015-08-12 | 南京大学 | Application of cleistanone O-(benzimidazolyl) ethyl derivative in preparation of anti-rhinitis drugs |
| CN105343044A (en) * | 2015-11-09 | 2016-02-24 | 南京广康协生物医药技术有限公司 | Composition and application thereof in anti-rhinitis drug |
-
2016
- 2016-06-13 CN CN201610416173.0A patent/CN106074526A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104814967A (en) * | 2015-04-15 | 2015-08-05 | 南京广康协生物医药技术有限公司 | Application of cleistanthus sumatranus ketone O-(1H-tetrazole base) ethyl ramification to preparing rhinitis-resisting medicine |
| CN104825468A (en) * | 2015-04-29 | 2015-08-12 | 南京大学 | Application of cleistanone O-(benzimidazolyl) ethyl derivative in preparation of anti-rhinitis drugs |
| CN105343044A (en) * | 2015-11-09 | 2016-02-24 | 南京广康协生物医药技术有限公司 | Composition and application thereof in anti-rhinitis drug |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104188980B (en) | O-(morpholinyl) ethyl derivative of Cleistanone Cleistanone, preparation method and its usage | |
| CN105287598A (en) | Composition and application of composition in medicine for resisting rhinitis | |
| CN104083379B (en) | The dimethylamine derivative of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone is preparing the application in anti-rhinitis medicament thing | |
| CN106074526A (en) | The composition of Schiglautone A derivative is used for preparing anti-rhinitis medicament thing | |
| CN104402964B (en) | O-(imidazole radicals) ethyl derivative of Cleistanone, preparation method and its usage | |
| CN105343044A (en) | Composition and application thereof in anti-rhinitis drug | |
| CN106074512A (en) | The composition of Ah draw'sing Bick acid triazolyl and 1H tetrazole radical derivative is for preparing anti-rhinitis medicament thing | |
| CN106236750A (en) | The application in anti-rhinitis medicament thing of the derivative composition of Schiglautone A | |
| CN105287568A (en) | Composition and application thereof to rhinitis resistant medicines | |
| CN105343080A (en) | Composition and application of composition in preparation of medicines for resisting rhinitis | |
| CN104825468A (en) | Application of cleistanone O-(benzimidazolyl) ethyl derivative in preparation of anti-rhinitis drugs | |
| CN104814967A (en) | Application of cleistanthus sumatranus ketone O-(1H-tetrazole base) ethyl ramification to preparing rhinitis-resisting medicine | |
| CN105250271A (en) | Composition and application of composition in rhinitis-resistant medicine | |
| CN106038544A (en) | Application of composition of Artalbic acid derivatives in preparation of anti-rhinitis drugs | |
| CN106038525A (en) | Composition of artalbic acid derivatives in preparation of anti-rhinitis medicines | |
| CN105998009A (en) | Application of composition of Salviskinone A benzimidazolyl and di(2-methylmercapto ethyl)amido derivatives in anti-rhinitis drugs | |
| CN106420749A (en) | Application of composition of diethylamino and piperazinyl derivatives of Harrisotone A in anti-rhinitis medicine | |
| CN105343091A (en) | Composition and application thereof in rhinitis resistant drugs | |
| CN106420713A (en) | Application of Atropurpuran derivative composition in anti-rhinitis drugs | |
| CN105920011A (en) | Application of composition of tetrahydropyrrolyl and morpholinyl derivatives of Virosaine A in anti-rhinitis medicines | |
| CN105232535A (en) | Composition and application thereof in anti-rhinitis drugs | |
| CN105395558A (en) | Composition and application of same to medicine resistant to rhinitis | |
| CN105434413A (en) | Composition and application thereof to anti-rhinitis medicine | |
| CN105287557A (en) | Composition and application thereof to rhinitis resistant medicines | |
| CN106074525A (en) | The composition of Schiglautone A derivative is used for preparing anti-acute renal failure medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20161109 |
|
| WD01 | Invention patent application deemed withdrawn after publication |