CN102001959A - Medicinal crystal as well as preparation method and application thereof - Google Patents
Medicinal crystal as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN102001959A CN102001959A CN2009100918775A CN200910091877A CN102001959A CN 102001959 A CN102001959 A CN 102001959A CN 2009100918775 A CN2009100918775 A CN 2009100918775A CN 200910091877 A CN200910091877 A CN 200910091877A CN 102001959 A CN102001959 A CN 102001959A
- Authority
- CN
- China
- Prior art keywords
- crystal
- preparation
- ethyl
- methoxynaphthalene
- pharmaceutical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 9
- 239000000843 powder Substances 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- YJYPHIXNFHFHND-UHFFFAOYSA-N agomelatine Chemical compound C1=CC=C(CCNC(C)=O)C2=CC(OC)=CC=C21 YJYPHIXNFHFHND-UHFFFAOYSA-N 0.000 claims description 11
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 10
- -1 acetamide compound Chemical class 0.000 claims description 6
- 239000012141 concentrate Substances 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 238000004364 calculation method Methods 0.000 claims description 5
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims description 4
- 229960003987 melatonin Drugs 0.000 claims description 4
- 208000017194 Affective disease Diseases 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 208000019022 Mood disease Diseases 0.000 claims description 3
- 206010029216 Nervousness Diseases 0.000 claims description 3
- 206010033664 Panic attack Diseases 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- 208000019906 panic disease Diseases 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 10
- 238000001228 spectrum Methods 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 11
- 239000000935 antidepressant agent Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 3
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000000634 powder X-ray diffraction Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 206010061623 Adverse drug reaction Diseases 0.000 description 1
- 206010013754 Drug withdrawal syndrome Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 229960002629 agomelatine Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000004455 differential thermal analysis Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000002484 serotonin 2C antagonist Substances 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001519 thymoleptic effect Effects 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a new N-[2-(7-methoxynaphthalene-1-base) ethyl] acetamide crystal and a preparation method thereof. The new N-[2-(7-methoxynaphthalene-1-base) ethyl] acetamide crystal is analyzed and measured through an X-ray powder spectrum method. A preparation prepared from the new N-[2-(7-methoxynaphthalene-1-base) ethyl] acetamide crystal has better dissolution rate and stability and is more suitable for patients in an attack stage.
Description
Technical field
The present invention relates to technical field of pharmaceuticals, be specifically related to a kind of N-[2-(7-methoxynaphthalene-1-yl) ethyl] ethanamide medicine new crystal and its production and use.
Background technology
Medicine when crystallization owing to influenced by various factors, intramolecularly or intermolecular bonding mode are changed, it is different to cause molecule or atom to be arranged at lattice vacancy, form different crystalline structure, the different crystal forms of same medicine may have remarkable difference at aspects such as outward appearance, solubleness, fusing point, dissolution rate, biological effectivenesses, thereby stability of drug, bioavailability and curative effect have been influenced, this kind phenomenon shows particularly evidently aspect oral solid formulation, and medicine different crystal forms phenomenon is one of important factor that influences drug quality and clinical efficacy.Therefore, be the most important thing in the drug research process to the research of medicine crystal formation.
N-[2-(7-methoxynaphthalene-1-yl) ethyl] ethanamide is by the development of French Servier company, is first melatonin 1,2 (MT
1, MT
2) receptor stimulant, be the melatonin analogue, also be the 5-HT2C receptor antagonist simultaneously, it belongs to the naphthalene nucleus compounds.This drug mechanism and the antidepressant drug that generally adopts at present as: selective serotonin reuptake inhibitor (SSRI) and serotonin-NRI (SNRI) are fully different: the antidepressant drug of SSRI and SNRI class thymoleptic is realized the antidepressant curative effect by increase serotonin concentration, but this has also brought many side effects, change as body weight, sexual dysfunction, drug withdrawal syndrome etc.And N-[2-(7-methoxynaphthalene-1-yl) ethyl] ethanamide directly and serotonin 2c (5HT2c) receptors bind of nerve synapse caudacoria, thereby bring into play its antidepressant curative effect, and do not increase the serotonin concentration of synaptic cleft.The mechanism of action of this uniqueness makes this medicine when bringing into play its antidepressant curative effect quickly and effectively, has avoided the generation of drug side effect to greatest extent.
Chinese patent CN200510071611.6, CN200610108936.7, CN200610108394.8, CN200610108395.2, CN200710096437.x, European patent EP 0447285, U.S. Pat 5318994, several different crystal forms of this medicine are studied, but all do not have according to quality product (such as dissolution rate, stability etc.), carry out deep research, therefore, it is imperative to study the outstanding new crystal of a kind of quality product.
Summary of the invention
For these reasons, our scientific research personnel is by secular scientific experiment, find N-[2-(7-methoxynaphthalene-1-yl) ethyl] a kind of new crystal of ethanamide medicine (being Agomelatine), with this new crystal is that the oral solid formulation of feedstock production has than existing crystal formation and has good dissolution degree, dissolution rate in particularly in 20 minutes can reach more than 90%, high temperature, high humidity, the experiment of high light equistability show that crystalline form of the present invention has better stability.
The present invention is achieved through the following technical solutions.
N-[2-(7-methoxynaphthalene-1-yl) ethyl] crystal of acetamide compound, it is characterized in that: measure 2 θ angles with X-ray powder atlas calculation, measure spacing d, relative intensity, described relative relative intensity is represented with the strongest ray percentage ratio:
Above-mentioned data are the data of characteristic peak.
Above-mentioned crystalline form includes but not limited to following preparation method: with N-[2-(7-methoxynaphthalene-1-yl) ethyl] ethanamide adds in the ethyl acetate, and dissolving is filtered, and concentrates, and crystal is separated out in cooling, and drying obtains crystal.
Its crystal purity more than or equal to 70% less than 100%.
Pharmaceutical composition comprises claim 1 or 2 described crystal.This pharmaceutical composition comprises above-mentioned crystal and at least a multi-form N-[2-(7-methoxynaphthalene-1-yl) ethyl] ethanamide, described multi-form amorphous, other crystalline forms that are selected from.
The pharmaceutical preparation of described preparation of pharmaceutical compositions.
The application of described pharmaceutical preparation in the disorderly medicine of preparation treatment melatonin energy.
The application of described pharmaceutical preparation in the following illness medicine of preparation treatment: sleep disordered, nervous, anxiety, affective disorder, depression, panic attack.
Above-mentioned numerical value is because objective factors such as instruments, method, environment, and the error of 2 θ angles and measure spacing d value and can have ± 1, relative intensity have ± 10% error.
Pharmaceutical preparation of the present invention comprises that load is not limited to conventional oral preparations such as tablet, capsule, pellet, granule, pill.
One, X-ray powder diffraction
Instrument: Japanese Rigaku D/max-2500 of science; X-ray powder diffraction instrument.
Experimental result:
Table 1
Two, differential thermal analysis
Instrument: the U.S. DSC-7 of PE company type differential scanning calorimeter
Experiment condition: 200 ℃ of ceiling temperatures; 20 ℃ of lower limit temperatures; 10 ℃/min of temperature rise rate
Experimental result:
The hot assay determination result data of table 2 table
| Fusing point (℃) | 108.61 |
| Summit temperature (℃) | 110.38 |
Three, infrared absorption spectrum (IR)
Instrument: U.S. power ﹠ light company fourier infrared spectrograph: Nicolet 5700
Sample preparation methods: KBr pressed disc method
Instrumental correction and calibrating: undertaken by 2005 editions two appendix of Chinese Pharmacopoeia
Determination data is as follows:
Table 3 infrared absorption spectrometry result data table
Four, dissolution determination method
Sample thief, according to dissolution method (2005 editions two appendix XC second methods of Chinese Pharmacopoeia), be dissolution medium with water 900ml, rotating speed is that per minute 50 changes, operation in accordance with the law, in the time of 30 minutes, to get solution and filter in right amount, precision is measured in subsequent filtrate 2ml to the 25ml measuring bottle, add water to scale, shake up,, measure absorbancy at the wavelength place of 230nm according to ultraviolet visible spectrophotometry (2005 editions two appendix IVA of Chinese Pharmacopoeia); Other gets the about 10mg of reference substance, and accurate the title decides, and puts in the 100ml measuring bottle, adds ethanol 5ml and makes dissolving, and dilute with water system shakes up to scale, and precision is measured in 1ml to the 50ml measuring bottle, adds water to scale, shake up, product solution is measured with method in contrast, calculates every stripping quantity.
Five, different crystal forms contrast experiment
1, dissolution rate comparative experiments
Experimental technique:
Experimental program 1: the crystalline form of Chinese patent CN200510071611.6 preparation;
Experimental program 2: the crystalline form of Chinese patent CN200610108936.7 preparation;
Experimental program 3: the crystalline form of Chinese patent CN200610108394.8 preparation;
Experimental program 4: the crystalline form of Chinese patent CN200610108395.2 preparation;
Experimental program 5: the crystalline form of Chinese patent CN200710096437.x preparation;
Experimental program 6: the crystalline form of European patent EP 0447285 preparation;
Experimental program 7: the crystalline form of U.S. Pat 5318994 preparations;
Experimental program 8: the new crystalline form of the present invention.
The crystalline form of above-mentioned different schemes is prepared into solid preparation according to same formulation method (supplementary product kind, consumption identical), according to above-mentioned dissolution determination method, measures, and experimental result sees Table 4:
Table 4 dissolution determination result
2, high temperature experiment
Experimental technique: experimental program is the same;
The crystalline form of above-mentioned different schemes is prepared into solid preparation according to same formulation method (supplementary product kind, consumption identical), place 60 ℃ thermostat container to place 10 days, in the 0th, 5,10 day sampling and measuring, with comparison in 0 day, the proterties of sample, dissolution rate, content and related substance no change.Measurement result sees Table 5.
Table 5 high temperature experimental result
Above-mentioned sample is carried out the experiment of high humidity, high light, and experimental data is close with above-mentioned experimental data, promptly experimental program 1-7 than the content of experimental program 8 descend many, its related substances rising many.
Experiment conclusion: above-mentioned experiment shows that crystalline form of the present invention and existing crystalline form relatively can be prepared the more outstanding product of quality.
Six, embodiment
Embodiment 1
N-[2-(7-methoxynaphthalene-1-yl) ethyl] the new crystal of acetamide compound, measure 2 θ angles with X-ray powder atlas calculation, measure spacing d, relative intensity, described relative intensity is represented with the strongest ray percentage ratio:
Above-mentioned data are the characteristic peak data.
Embodiment 2
N-[2-(7-methoxynaphthalene-1-yl) ethyl] crystal of acetamide compound, it measures 2 θ angles with X-ray powder atlas calculation, measures spacing d, relative intensity, and described relative intensity is represented with the strongest ray percentage ratio:
Above-mentioned data are the characteristic peak data.
Embodiment 3
N-[2-(7-methoxynaphthalene-1-yl) ethyl] crystal of acetamide compound, it is characterized in that: measure 2 θ angles with X-ray powder atlas calculation, measure spacing d, relative intensity, described relative intensity is represented with the strongest ray percentage ratio:
Above-mentioned data are the characteristic peak data.
The new crystalline form purity of the foregoing description 1-3 more than or equal to 95% less than 100%.
The pharmaceutical preparation of the new crystal preparation of the foregoing description 1-3; The application of pharmaceutical preparation in the disorderly medicine of preparation treatment melatonin energy; The application of pharmaceutical preparation in the following illness medicine of preparation treatment: sleep disordered, nervous, anxiety, affective disorder, depression, panic attack.
The new crystalline preparation method of the foregoing description 1-3 includes but not limited to following:
Embodiment 4
With N-[2-(7-methoxynaphthalene-1-yl) ethyl] ethanamide adds in the ethyl acetate, and dissolving is filtered, and concentrates, and crystal is separated out in cooling, and drying obtains crystal.
Embodiment 5
With N-[2-(7-methoxynaphthalene-1-yl) ethyl] ethanamide adds in ethyl acetate and the sherwood oil mixed solution, and dissolving is filtered, and concentrates, and crystal is separated out in cooling, and drying obtains crystal.
Embodiment 6
With N-[2-(7-methoxynaphthalene-1-yl) ethyl] ethanamide adds in ethyl acetate and the acetone mixed solution, and dissolving is filtered, and concentrates, and crystal is separated out in cooling, and drying obtains crystal.
Embodiment 7
With N-[2-(7-methoxynaphthalene-1-yl) ethyl] ethanamide adds in ethyl acetate and the normal hexane mixed solution, and dissolving is filtered, and concentrates, and crystal is separated out in cooling, and drying obtains crystal.
Annotate: the present invention's concrete technical scheme required for protection is not limited to the concrete combination of the expressed technical scheme of the foregoing description.
Claims (7)
- (1.N-[2-7-methoxynaphthalene-1-yl) ethyl] crystal of acetamide compound, it is characterized in that: measure 2 θ angles with X-ray powder atlas calculation, measure spacing d, relative intensity, described relative intensity is represented with the strongest ray percentage ratio:
- 2. crystal according to claim 1, its preparation method is: with N-[2-(7-methoxynaphthalene-1-yl) ethyl] ethanamide adds in the ethyl acetate, and dissolving is filtered, and concentrates, and crystal is separated out in cooling, and drying obtains crystal.
- 3. crystal according to claim 1 and 2, its purity more than or equal to 70% less than 100%.
- 4. pharmaceutical composition comprises claim 1 or 2 described crystal.
- 5. the pharmaceutical preparation of preparation of pharmaceutical compositions according to claim 4.
- 6. the application of pharmaceutical preparation according to claim 5 in the disorderly medicine of preparation treatment melatonin energy.
- 7. the application of pharmaceutical preparation according to claim 5 in the following illness medicine of preparation treatment: sleep disordered, nervous, anxiety, affective disorder, depression, panic attack.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910091877.5A CN102001959B (en) | 2009-09-01 | 2009-09-01 | Medicinal crystal as well as preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910091877.5A CN102001959B (en) | 2009-09-01 | 2009-09-01 | Medicinal crystal as well as preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102001959A true CN102001959A (en) | 2011-04-06 |
| CN102001959B CN102001959B (en) | 2014-07-02 |
Family
ID=43809701
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910091877.5A Active CN102001959B (en) | 2009-09-01 | 2009-09-01 | Medicinal crystal as well as preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102001959B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102557979A (en) * | 2010-12-16 | 2012-07-11 | 北大方正集团有限公司 | Agomelatine crystal form, as well as preparation method, application and medicinal composition thereof |
| EP3075724A1 (en) | 2015-03-31 | 2016-10-05 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Solid form of agomelatine |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0447285A1 (en) * | 1990-02-27 | 1991-09-18 | Adir Et Compagnie | Naphthalene derivatives, procedure for their preparation and pharmaceutical compositions containing them |
| CN1680284A (en) * | 2004-02-13 | 2005-10-12 | 瑟维尔实验室 | New process for the synthesis and new crystalline form of agomelatine and pharmaceutical compositions containing it |
| CN1907958A (en) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | New crystalline form v of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
| CN1907957A (en) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | Crystalline form iv of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
| CN1907959A (en) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | New crystalline form iii of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
| CN101429134A (en) * | 2007-11-09 | 2009-05-13 | 瑟维尔实验室 | New crystalline form VI of agomelatine, method of preparation and pharmaceutical compositions thereof |
-
2009
- 2009-09-01 CN CN200910091877.5A patent/CN102001959B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0447285A1 (en) * | 1990-02-27 | 1991-09-18 | Adir Et Compagnie | Naphthalene derivatives, procedure for their preparation and pharmaceutical compositions containing them |
| US5318994A (en) * | 1990-02-27 | 1994-06-07 | Adir Et Compagnie | N-[2-(7-lower-alkoxynaphth-1-yl)ethyl]benzamides |
| CN1680284A (en) * | 2004-02-13 | 2005-10-12 | 瑟维尔实验室 | New process for the synthesis and new crystalline form of agomelatine and pharmaceutical compositions containing it |
| CN101041629A (en) * | 2004-02-13 | 2007-09-26 | 瑟维尔实验室 | New process for the synthesis and new crystalline form of agomelatine and pharmaceutical compositions containing it |
| CN1907958A (en) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | New crystalline form v of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
| CN1907957A (en) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | Crystalline form iv of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
| CN1907959A (en) * | 2005-08-03 | 2007-02-07 | 瑟维尔实验室 | New crystalline form iii of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
| CN101429134A (en) * | 2007-11-09 | 2009-05-13 | 瑟维尔实验室 | New crystalline form VI of agomelatine, method of preparation and pharmaceutical compositions thereof |
Non-Patent Citations (1)
| Title |
|---|
| 唐家邓，等: "阿戈美拉汀的合成", 《中国医药工业杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102557979A (en) * | 2010-12-16 | 2012-07-11 | 北大方正集团有限公司 | Agomelatine crystal form, as well as preparation method, application and medicinal composition thereof |
| CN102557979B (en) * | 2010-12-16 | 2014-11-26 | 北大方正集团有限公司 | Agomelatine crystal form, as well as preparation method, application and medicinal composition thereof |
| EP3075724A1 (en) | 2015-03-31 | 2016-10-05 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Solid form of agomelatine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102001959B (en) | 2014-07-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SA112330595B1 (en) | New co-crystals of agomelatine,a process for their preparation and pharmaceutical compositions containing them | |
| Roumeli et al. | Compatibility study between trandolapril and natural excipients used in solid dosage forms | |
| CN110483486A (en) | A kind of western Tenylidone of Austria coughs up hydrochlorate crystal form and preparation method thereof | |
| CA3182373A1 (en) | Composition for use in the treatment of apol1-associated disease | |
| CN106543072A (en) | Mo Fanselin compounds | |
| CN107428779A (en) | Mi Zuo Bing oxazines crystal, the pharmaceutical composition containing the crystal and the method for preparing the crystal | |
| EP3569590A1 (en) | (r)-4-hydroxy-2-oxo-1-pyrrolidineacetamide crystal form, preparation method therefor, and application thereof | |
| TW201213325A (en) | Crystalline forms of pyrimidio [6,1-A] isoquinolin-4-one compounds | |
| Gong et al. | Structure, characterization, solubility and stability of podophyllotoxin polymorphs | |
| AU2012231547B2 (en) | New crystal form VII of agomelatine, preparation method and use thereof and pharmaceutical composition containing same | |
| CN102001959B (en) | Medicinal crystal as well as preparation method and application thereof | |
| AU2012231548B2 (en) | Mixed crystal agomelatine (Form-VIII), preparation method and use thereof and pharmaceutical composition containing same | |
| CN102766097A (en) | Edaravone A-type crystal and preparation method thereof | |
| TWI772382B (en) | Analogs of deutetrabenazine, their preparation and use | |
| CN104447771A (en) | Stable asenapine maleate sublingual compound | |
| CN106543124A (en) | dapagliflozin compound | |
| CN102030743B (en) | Iloperidone crystal, and preparation method and medicinal composition thereof | |
| CN102344360B (en) | Preparation method of arginine dexibuprofen | |
| JP2013509357A (en) | 3- (Substituted dihydroisoindol-2-yl) -2,6-piperidinedione polycrystal and medicinal composition | |
| CN105646520A (en) | Stable Halaven compound | |
| CN108542898A (en) | Purposes of the cajanin and combinations thereof in preparing medicament for treatment of depression | |
| WO2020233226A1 (en) | B crystal form of tetrahydrothienopyridine compound, preparation method therefor, composition and application | |
| Ledeti et al. | Thermal stability of desipramine and imipramine | |
| CN104650086A (en) | Ponatinib hydrochloride compound | |
| CN102557979B (en) | Agomelatine crystal form, as well as preparation method, application and medicinal composition thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| DD01 | Delivery of document by public notice | ||
| DD01 | Delivery of document by public notice |
Addressee: Sun Dejie Document name: payment instructions |
|
| DD01 | Delivery of document by public notice | ||
| DD01 | Delivery of document by public notice |
Addressee: Sun Dejie Document name: Notice of Termination of Patent Rights |