CN104523702A - Application of phenylalanine cyclopentanoperhydro-phenanthrene ester in preparation of hypotensor - Google Patents
Application of phenylalanine cyclopentanoperhydro-phenanthrene ester in preparation of hypotensor Download PDFInfo
- Publication number
- CN104523702A CN104523702A CN201410777381.4A CN201410777381A CN104523702A CN 104523702 A CN104523702 A CN 104523702A CN 201410777381 A CN201410777381 A CN 201410777381A CN 104523702 A CN104523702 A CN 104523702A
- Authority
- CN
- China
- Prior art keywords
- phenylalanine
- ester
- cyclopentanoperhydro
- luxuriant
- pentamethylene
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
Abstract
The invention discloses ACE inhibitory activity of 2-t-butyloxycarboryl-3-phenylpropionic acid [(2S)-(3S,10R,13R)-10,13-dimethyl-17-((2R,E)-5,6-dimethylpept-3-en-2-yl)-2,3,4,9,10,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ester] (short for phenylalanine cyclopentanoperhydro-phenanthrene ester B) and application of the phenylalanine cyclopentanoperhydro-phenanthrene ester B in preparation of hypotensor, belonging to novel medicinal application of traditional Chinese medicine active ingredients.
Description
Technical field
The invention discloses phenylalanine Pentamethylene. and the ACE inhibitory activity of the luxuriant and rich with fragrance ester B of many hydrogen and preparing the application in Altace Ramipril.Belong to the new medicine use of Effective Component of Chinese Medicine.
Background technology
Hypertension increases clinical syndrome for main manifestations with systemic arterial pressure, is modal cardiovascular disease.The pathogenic factors of essential hypertension mainly contains two large classes, and a class is endogenous cause of ill, as heredity; Another kind of is exopathogenic factor, as psychentonia, Sal too much, smoking, obesity, excessive drinking, shortage motion etc.Long-term hypertension can have influence on the function of the organs such as the heart, brain, kidney, finally causes the exhaustion of these organ dysfunctions.Hypertension belongs to frequently-occurring disease, the eighties in last century, and Chinese Hypertension incidence is 7.7%; To the beginning of this century, rise to 18.8% rapidly; And nearly 10 years, hypertensive prevalence increases 31%.At present, China hypertensive patient estimates more than 200,000,000, and this trend still can continue continuity, unlikely occurs reversing in short-term.If or else controlled, will 50% be increased in 15 from now on year.Antihypertensive drugs kind mainly comprises diuretic, beta-blocker, calcium channel blocker, angiotensin converting enzyme inhibitor, angiotensin-ii receptor blocker.These medicines have certain side effect, as Cardiac depression, Developmental and Metabolic Disorder, kidney damage etc.And the Altace Ramipril with China's independent intellectual property right is less.
" ergosterol ", also known as " ergosterol ", ergosterol is one of steroid.This compound can be used for Biochemical Research, the same vitamin D2 of partial action.Angle sterin is the important composition part of microbial cell film, and to the integrity guaranteeing cell membrane, the activity of membrane bound enzyme, the mobility of film, cell viability and cellular material transport etc. play an important role.Produce the intermediate of hormone medicine, can be used to produce cortisone.There is the effect of vitamin D2.
Seminar, in Altace Ramipril precursor screening process, finds that ergosterol has certain angiotensin converting enzyme (ACE) inhibitory action (half suppression ratio (IC of ACE
50) reach 892 μ g/mL), and 2-t-butoxycarbonyl amino-3-phenylpropionic acid (2S) relevant to its structure-(3S, 10R, 13R)-10, 13-dimethyl-17-((2R, E)-5, 6-dimethyl-g-3-alkene-2-base)-2, 3, 4, 9, 10, 11, 12, 13, 14, 15, 16, 17-ten dihydro-1H-ring penta [a] phenanthrene-3-ester [(2S)-(3S, 10R, 13R)-17-((2R, E)-5, 6-dimethylhept-3-en-2-yl)-10, 13-dimethyl-2, 3, 4, 9, 10, 11, 12, 13, 14, 15, 16, 17-dodecahydro-1H-cyclopenta [a] phenanthren-3-yl 2-((tert-butoxycarbonyl) amino)-3-phenylpropanoate], be called for short phenylalanine Pentamethylene. and the luxuriant and rich with fragrance ester B of many hydrogen, this compound is to the half suppression ratio (IC of ACE after measured
50) reaching 17 μ g/mL, its activity is nearly 60 times of ergosterol.The luxuriant and rich with fragrance ester B of phenylalanine Pentamethylene. many hydrogen is expected to become new Altace Ramipril.
Summary of the invention
The invention provides 2-t-butoxycarbonyl amino-3-phenylpropionic acid (2S)-(3S, 10R, 13R)-10,13-dimethyl-17-((2R, E)-5,6-dimethyl-g-3-alkene-2-base)-2,3,4,9,10,11,12,13,14,15,16,17-ten dihydro-1H-ring penta [a] phenanthrene-3-ester (being called for short phenylalanine Pentamethylene. and the luxuriant and rich with fragrance ester B of many hydrogen) is preparing the purposes in Altace Ramipril.The chemical constitution of the luxuriant and rich with fragrance ester B of phenylalanine Pentamethylene. many hydrogen as shown in the formula:
When the present invention is for the preparation of the hypertensive medicine for the treatment of, its oral or parenteral is all safe.In oral situation, it can any conventionally form administration, as powder, granule, tablet, capsule, pill, solution, suspension, syrup, buccal tablets, sublingual lozenge etc.; When this drugs for parenteral delivery, any conventionally form can be taked, such as intravenous injection agent, ointment, suppository and inhalant etc.
It is form together with excipient by effective ingredient monomer or effective ingredient and solid or liquid that the present invention prepares the hypertensive medicine for the treatment of, the excipient of solid used herein or liquid is well known in the art, lift several object lesson below, powder is powder agent for oral administration, its excipient has lactose, starch, paste essence, calcium carbonate, synthesis or puritan filler aluminum, magnesium oxide, magnesium stearate, sodium bicarbonate, dry yeast etc.; The excipient of solution has water, glycerol, 1,2-PD, simple syrup, ethanol, ethylene glycol, Polyethylene Glycol, Sorbitol etc.; The excipient of ointment can use fatty oil, agnolin, vaseline, glycerol, Cera Flava, wood cured, white oil, resin, the senior water-repelling agent that is combined into such as cured or hydrophilizing agent.
Beneficial effect of the present invention is, the luxuriant and rich with fragrance ester B of phenylalanine Pentamethylene. many hydrogen can be used for preparing Altace Ramipril, has feature evident in efficacy, its IC suppressed ACE
5017 μ g/mL can be reached.Following experiment confirms phenylalanine Pentamethylene. and this biological activity of the luxuriant and rich with fragrance ester B of many hydrogen.
Detailed description of the invention
embodiment:
The structure of the luxuriant and rich with fragrance ester B of phenylalanine Pentamethylene. many hydrogen is determined and phenylalanine Pentamethylene. the ACE inhibitory activity of luxuriant and rich with fragrance ester B and ergosterol of many hydrogen measure.
1. phenylalanine Pentamethylene. many hydrogen luxuriant and rich with fragrance ester B Structural Identification:
MS: its molecular ion peak of mass spectroscopy is 643.4, in conjunction with IR,
1h NMR,
13c NMR determines that its molecular formula is C
42h
61nO
4.
IR spectrum: 34353 cm
-1stretching vibration peak (the υ of amino nitrogen hydrogen bond
nH), 3081 cm
-1for the hydrocarbon stretching vibration peak (υ of double bond
cH), 2988-2874 cm
-1for the stretching vibration peak (υ of saturated alkane C-H bond
cH), prove the existence of saturated alkane group; 1729 cm
-1for the stretching vibration peak (υ of carbonyl
c=O), illustrate in this compound to there is carbonyl; 1686 cm
-1for υ
c=C, the existence of carbon-carbon double bond is described; 1603 cm
-1, 1582 cm
-1, 1502 cm
-1for phenyl ring carbon-carbon double bond skeleton stretching vibration peak (υ
c=C); 1381 cm
-1, 1370 cm
-1for methyl deformation vibration peak (
δ cH3).
1h NMR (300 MHz, CDCl
3) δ ppm:7.296 (
m, 2H), 7.290 (
m, 2H), 7.176 (
m, 1H) and be single-substituted hydrogen signal, 7.150 (
s, 1H) and be amino active hydrogen signal, 5.571 (
dd, 1H,
j=1.8,5.7Hz), 5.381 (
m, 1H), 5.210 (
dd, 1H,
j=4.2,7.2Hz), 5.190 (
dd, 1H,
j=4.2,7.2Hz) be steroidal parent nucleus 6,7,3 ', 4 ' position alkene hydrogen signal, 5.018 (
d, 1H,
j=8.1Hz) for connecting hydrogen signal on amino-carbon, 4.725 (
m, 1H) and be hydrogen signal on steroidal parent nucleus 3 even oxygen carbon, 4.573 (
dd, 1H,
j=5.4,8.1Hz), 3.088 (
d, 1H,
j=5.4Hz) be the signal of methine in phenylalanine radical, 1.421 (
s, 9H) and be three methyl hydrogen signals in 2-tertbutyloxycarbonyl, 1.051 (
d, 3H,
j=6.6Hz), 0.939 (
s, 3H), 0.933 (
d, 3H,
j=6.9Hz), 0.854 (
d, 3H,
j=6.6Hz), 0.839 (
d, 3H,
j=6.6Hz), 0.630 (
s, 3H) and be 6 methyl hydrogen signals on steroidal parent nucleus and 17 side chains, 2.371 ~ 0.546 is hydrogen signal in steroidal parent nucleus and 17 other saturated carbon of side chain, and above data illustrate the existence of steroidal structure and 2-t-butoxycarbonyl amino-3-phenylpropionic acid group.
13c NMR (75 MHz, CDCl
3) δ ppm: carbon modal data provides 42 carbon signals altogether, specific as follows.171.24 be carbonyl carbon signals in alanine; 155.01 is carbonyl carbon signals in 2-tertbutyloxycarbonyl, 136.02,129.36(× 2), 128.39(× 2), 126.88 be phenyl ring carbon signal in phenylalanine, 79.76 is 42.73 is connect oxygen quaternary carbon signal in 2-tertbutyloxycarbonyl, 28.23 is 3 methyl carbon signals in 2-tertbutyloxycarbonyl, 54.44,36.35 is two saturated carbon signals in phenylalanine, and above carbon signal constitutes 2-t-butoxycarbonyl amino-3-phenylpropionic acid group; 138.11,120.29,116.15,141.59,135.46,131.90 is steroidal parent nucleus C5, C6, C7, C8, C3 ', C4 ' unsaturated carbon signal, 73.95 is steroidal parent nucleus 3 even oxygen carbon signal, 55.62,54.44,45.92,42.74(× 2), 40.36,38.92,37.72,36.35,36.57,33.01,28.23,27.94,22.91,21.04,20.94,19.89,19.58,17.54,16.08,11.99 be steroidal parent nucleus and 17 other saturated carbon signals of side chain.
In conjunction with
1h NMR,
13c NMR and IR spectrum are comprehensively analyzed further and are determined that this compound is 2-t-butoxycarbonyl amino-3-phenylpropionic acid (2S)-(3S, 10R, 13R)-10, 13-dimethyl-17-((2R, E)-5, 6-dimethyl-g-3-alkene-2-base)-2, 3, 4, 9, 10, 11, 12, 13, 14, 15, 16, 17-ten dihydro-1H-ring penta [a] phenanthrene-3-ester [(2S)-(3S, 10R, 13R)-17-((2R, E)-5, 6-dimethylhept-3-en-2-yl)-10, 13-dimethyl-2, 3, 4, 9, 10, 11, 12, 13, 14, 15, 16, 17-dodecahydro-1H-cyclopenta [a] phenanthren-3-yl 2-((tert-butoxycarbonyl) amino)-3-phenylpropanoate], be called for short phenylalanine Pentamethylene. and the luxuriant and rich with fragrance ester B of many hydrogen, the concrete NMR signals assignment of this compound is as follows:
1h NMR (300 MHz, CDCl
3) δ ppm:7.296 (
m, 2H, 6 ' ', 8 ' '-H), 7.290 (
m, 2H, 5 ' ', 9 ' '-H), 7.176 (
m, 1H, 7 ' '-H), 7.150 (
s, 1H, 2 ' '-NH), 5.571 (
dd, 1H,
j=1.8,5.7Hz, 6-H), 5.381 (
m, 1H, 7-H), 5.210 (
dd, 1H,
j=4.2,7.2Hz, 3 '-H), 5.190 (
dd, 1H,
j=4.2,7.2Hz, 4 '-H), 5.018 (
d, 1H,
j=8.1Hz, 2 ' '-H), 4.725 (
m, 1H, 3-H), 4.573 (
dd, 1H,
j=5.4,8.1Hz, 3 ' '-Ha), 3.088 (
d, 1H,
j=5.4Hz, 3 ' '-Hb), 1.421 (
s, 9H, 2 ' ' '-CH
3), 1.051 (
d, 3H,
j=6.6Hz, 2 '-CH
3), 0.939 (
s, 3H, 10-CH
3), 0.933 (
d, 3H,
j=6.9Hz, 5 '-CH
3), 0.854 (
d, 3H,
j=6.6Hz, 6 '-CH
3), 0.839 (
d, 3H,
j=6.6Hz, 7 '-H), 0.630 (
s, 3H, 13-CH
3), 2.371 ~ 0.546 be hydrogen signal in steroidal parent nucleus and 17 other saturated carbon of side chain.
13C NMR (75 MHz, CDCl
3) δppm：171.24 (C1’’)、155.01 (C1’’’)、136.02 (C4’’)、129.36 (C6’’,8’’)、128.39 (C5’’,9’’)、126.88 (C7’’)、79.76 (C2’’’)、28.23 (2’’’, 2’’’, 2’’’- CH
3)、54.44 (C2’’)、36.35 (C3’’)、138.11 (C5)、120.29 (C6)、116.15 (C7)、141.59 (C8)、135.46 (C3’)、131.90 (C4’)、73.95 (C3)、55.62 (C17)、54.44 (C14)、45.92 (C9)、42.74 (C13,5’)、40.36 (C2’)、38.92 (C12)、37.72 (C1)、36.35 (C4)、36.57 (C10)、33.01 (C6’)、28.23 (C2)、27.94 (C16)、22.91 (C15)、21.04 (C11)、20.94 (C7’)、19.89 (6’-CH
3)、19.58 (C1’)、17.54 (5’-CH
3)、16.08 (10-CH
3)、11.99 (13-CH
3)。
2.ACEI inhibit activities is tested
Renin angiotensin aldosterone system (RAS) plays an important role in hypertension generation, development, and its angiotensin I is main effector peptide.ACEI suppresses angiotensinⅠ to be converted to angiotensinⅡ, not deactivation Kallidin I, produces pressure reduction effect.This experiment adopts external ACE inhibitory activity experimental evaluation phenylalanine Pentamethylene. and the hypotensive activity of the luxuriant and rich with fragrance ester B and the ergosterol close with its structure of many hydrogen.Specific experiment method and result as follows.
The preparation of 2.1 ACE
Fresh Pulmonis Sus domestica is met cold 0.9%NaCL solution rinse well, wash away trachea, fat, be cut into small pieces, remove a certain amount of Pulmonis Sus domestica tissue, carrying out homogenate with meeting cold PH 8.3, the 0.1 mol/L borate buffer solution 5 times of volumes that contain, homogenate being placed in refrigerator lixiviate 5 hours.Centrifugal at 4 DEG C (8000rmp) centrifugal 15 min, obtain crude extract (supernatant).Lyophilization is stand-by.
The preparation of 2.2 need testing solutions
Get the extract solution that 10mg sample (luxuriant and rich with fragrance ester B or ergosterol of phenylalanine Pentamethylene. many hydrogen) is mixed with 5 variable concentrations.According to the form below order adds solution, after 37 DEG C of insulation 5 min, add 5 μ L ACE solution and start reaction, after 37 DEG C of insulation 30 min, add 1 mol/L HCl solution 300 μ L cessation reaction, centrifugal 10 min of 10 000 r/min, draw supernatant as need testing solution.
HHL solution: get appropriate HHL, adds borate buffer solution and is mixed with the HHL solution that concentration is 5 mmol/L.
2.3 hippuric acid assays
Chromatographic condition: LC 3000-C
18chromatographic column (4.6 mm × 250 mm, 5 μm) (Shen, large Liaanjiang county separation science technology company), mobile phase methanol: trifluoroacetic acid water (0.01%), eluent gradient is (0 min, 60%B; 3 min, 60%B; 3.01 min, 100%B; 6 min, 100%B; 6.01 min, 60%B; 8 min, 60%B), determined wavelength 228 nm, flow velocity 1.0 mL/min, column temperature 25 DEG C, sample size 20 μ L.
Hippuric acid contrast liquid: get hippuric acid appropriate, add borate buffer solution and be mixed with the hippuric acid reference substance solution that concentration is 0.1 mmol/L.
Accurate absorption need testing solution and hippuric acid reference substance solution inject high performance liquid chromatograph respectively, and record chromatogram, calculates the content of hippuric acid by one point external standard method.
The calculating of 2.4 ACE suppression ratio
Computing formula is as follows: R=(A-B)/A × 100%
In formula, A and B is respectively the peak area of blank group and test group hippuric acid.
To ACE inhibitory activity IC
50value represents, IC
50value adopts SPSS computed in software to obtain.
2.5 ACE inhibit activities result and conclusions
Adopt above experiment to obtain phenylalanine Pentamethylene. and luxuriant and rich with fragrance ester B and ergosterol of many hydrogen to the IC of ACE inhibitory activity
50value.The luxuriant and rich with fragrance ester B of phenylalanine Pentamethylene. many hydrogen is to the IC of ACE
50=17 μ g/mL, and ergosterol is to the IC of ACE
50=892 μ g/mL.Experimental result shows phenylalanine Pentamethylene. and the luxuriant and rich with fragrance ester B of many hydrogen has stronger ACE inhibitory activity, and it is nearly 60 times of Verbindung rgosterol to the inhibitory action of ACE.The luxuriant and rich with fragrance ester B of this phenylalanine Pentamethylene. many hydrogen becomes new Altace Ramipril by being expected to.
Claims (1)
1.2-t-butoxycarbonyl amino-3-phenylpropionic acid (2S)-(3S, 10R, 13R)-10,13-dimethyl-17-((2R, E)-5,6-dimethyl-g-3-alkene-2-base)-2,3,4,9,10,11,12,13,14,15,16,17-ten dihydro-1H-ring penta [a] phenanthrene-3-ester is preparing the application in Altace Ramipril.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410777381.4A CN104523702A (en) | 2014-12-17 | 2014-12-17 | Application of phenylalanine cyclopentanoperhydro-phenanthrene ester in preparation of hypotensor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410777381.4A CN104523702A (en) | 2014-12-17 | 2014-12-17 | Application of phenylalanine cyclopentanoperhydro-phenanthrene ester in preparation of hypotensor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104523702A true CN104523702A (en) | 2015-04-22 |
Family
ID=52839461
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410777381.4A Pending CN104523702A (en) | 2014-12-17 | 2014-12-17 | Application of phenylalanine cyclopentanoperhydro-phenanthrene ester in preparation of hypotensor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104523702A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011078323A1 (en) * | 2009-12-25 | 2011-06-30 | 花王株式会社 | Active oxygen production inhibitor and anti-hypertensive agent |
| CN102558270A (en) * | 2012-03-09 | 2012-07-11 | 辽宁新中现代医药有限公司 | 20(S) and 20(R)-dammarane-3beta,12beta,20,25-tetrol derivative and preparation method and application thereof |
| CN103435676A (en) * | 2013-09-12 | 2013-12-11 | 河南工业大学 | Phytosterol phosphorylation amino-acid ester derivative and synthetic method thereof |
| CN103724392A (en) * | 2013-12-18 | 2014-04-16 | 江南大学 | Preparation method of amino acid phytosterol ester hydrochloride |
-
2014
- 2014-12-17 CN CN201410777381.4A patent/CN104523702A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011078323A1 (en) * | 2009-12-25 | 2011-06-30 | 花王株式会社 | Active oxygen production inhibitor and anti-hypertensive agent |
| CN102558270A (en) * | 2012-03-09 | 2012-07-11 | 辽宁新中现代医药有限公司 | 20(S) and 20(R)-dammarane-3beta,12beta,20,25-tetrol derivative and preparation method and application thereof |
| CN103435676A (en) * | 2013-09-12 | 2013-12-11 | 河南工业大学 | Phytosterol phosphorylation amino-acid ester derivative and synthetic method thereof |
| CN103724392A (en) * | 2013-12-18 | 2014-04-16 | 江南大学 | Preparation method of amino acid phytosterol ester hydrochloride |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI377064B (en) | Compounds from mycelium of antrodia cinnamomea and use thereof | |
| TWI580689B (en) | A sterol derivatives, preparation method and use thereof | |
| CN104523702A (en) | Application of phenylalanine cyclopentanoperhydro-phenanthrene ester in preparation of hypotensor | |
| CN110927279B (en) | Method for separating imidapril hydrochloride related substances | |
| CN104402960B (en) | The luxuriant and rich with fragrance ester A of furancarboxylic acid pentamethylene many hydrogen and extracting method thereof and pharmaceutical use | |
| CN103884803B (en) | Preparation method for enrofloxacin molecular imprinting monolithic column | |
| CN103012596A (en) | Endomorphin-derived peptide with blood-brain barrier permeability as well as synthesis and application of endomorphin-derived peptide | |
| CN104402962B (en) | The luxuriant and rich with fragrance ester C of Thioctic Acid pentamethylene many hydrogen and extracting method thereof and pharmaceutical use | |
| CN107141335B (en) | Cyclopeptide compound and preparation method and application thereof | |
| TWI299663B (en) | Methods of treatment | |
| CN102286011B (en) | Pyrrolidine botonate ester depeptidyl peptidase inhibitors and its pharmaceutical composition | |
| CN112028887B (en) | Penehyclidine hydrochloride impurity and preparation method thereof | |
| CN104558085B (en) | Naphthoic acid Pentamethylene. many hydrogen phenanthrene ester B and extracting method thereof and medicinal usage | |
| CN116559458A (en) | Active natural product target spot identification method based on PROTAC protein targeted degradation technology and PROTAC compound | |
| AU2003211602A1 (en) | Diagnostic reagent for evaluation of pharmacological effect of medicine, and method and reagent for screening pharmaceutical agents comprising enzyme, enzyme inhibitor or receptor ligand and/or prodrugs thereof for one having high medicative efficacy and/or small side effect | |
| CN104402959B (en) | The luxuriant and rich with fragrance ester B of succsinic acid dicyclo pentane many hydrogen and extracting method thereof and pharmaceutical use | |
| CN104434927A (en) | Application of bicyclopentanoperhydrophenanthrene malonate B in preparing hypotensive drugs | |
| CN104387434B (en) | The luxuriant and rich with fragrance ester B of tetrahydrochysene furoic acid pentamethylene many hydrogen and extracting method thereof and pharmaceutical use | |
| CN105367549A (en) | Lenalidomide-gallic acid co-crystal and preparation method therefor | |
| CN105837514B (en) | The preparation method of Fimasartan impurity of the drug | |
| CN104387437B (en) | The luxuriant and rich with fragrance ester A of indolylacetic acid pentamethylene many hydrogen and extracting method thereof and pharmaceutical use | |
| CN104402961B (en) | The luxuriant and rich with fragrance ester A of tetrahydrochysene furoic acid pentamethylene many hydrogen and extracting method thereof and pharmaceutical use | |
| CN105796551A (en) | ACE inhibitor neolignan composition as well as preparation method and application thereof | |
| CN107501211A (en) | The common amorphous substance of Docetaxel flavones | |
| CN104530167B (en) | The luxuriant and rich with fragrance ester A of Whitfield's ointment pentamethylene many hydrogen and extracting method thereof and pharmaceutical use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 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: 20150422 |
|
| WD01 | Invention patent application deemed withdrawn after publication |