CN106336444A - New crystal form of estradiol - Google Patents
New crystal form of estradiol Download PDFInfo
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- CN106336444A CN106336444A CN201610709151.3A CN201610709151A CN106336444A CN 106336444 A CN106336444 A CN 106336444A CN 201610709151 A CN201610709151 A CN 201610709151A CN 106336444 A CN106336444 A CN 106336444A
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- crystal formation
- preparation
- ethinyloestradiol
- dioxane
- pharmaceutical composition
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0081—Substituted in position 17 alfa and 17 beta
- C07J1/0088—Substituted in position 17 alfa and 17 beta the substituent in position 17 alfa being an unsaturated hydrocarbon group
- C07J1/0096—Alkynyl derivatives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a new crystal form of estradiol containing 2.5 water molecules, a crystal form X2 for short. The invention also discloses a preparation method of the crystal form. The crystal form X2 of estradiol has good stability and can be used for preparation of a medicinal preparation.
Description
Technical field
The invention belongs to medicinal chemistry art, it is related to a kind of novel crystal forms of medicine and in particular to a kind of novel crystal forms of ethinyloestradiol
x2.
Background technology
Ethinyloestradiol (ethinylestradiol), its chemistry is entitled: 3- hydroxy-19-nor -17 α-pregnant steroid -1, and 3,5
(10)-triolefin -20- alkynes -17- alcohol.For orally active potent estrogen, its activity is 7~8 times, diethylstilbestrol of estradiol
20 times.It is clinically used for paramenia, such as amenorrhoea, hypomenorrhia, functional uterine bleeding, climacteric syndrome, developing womb
Incomplete, prostate cancer etc..With progesterone compatibility, there is synergy to ovulation inhibition, strengthen contraceptive effect, be in oral contraceptive
The most frequently used estrogen.
Drug crystal forms research and the research and development of medicine solid-state have very important meaning in pharmacy industry.Drug molecule generally has not
With solid forms, including salt, polycrystalline, eutectic, amorphous, hydrate and solvate;The not isomorphous of same drug molecule
Type, in crystal structure, stability, the properties such as productibility and bioavilability might have significant difference, thus directly
The curative effect of impact medicine and exploitability.Therefore, any one drug research and development, is required for carrying out comprehensive and systematic polymorphic sieve
Choosing, finds crystal formation as much as possible, then carries out in-depth study using various solid-state approach to these crystal formations, thus finding
It is suitable for the crystal formation of exploitation.
Content of the invention
An object of the present invention is to provide a kind of novel crystal forms of ethinyloestradiol.
The second object of the present invention is to provide the preparation method of above-mentioned crystal formation.
The second object of the present invention is to provide the pharmaceutical composition of above-mentioned crystal formation preparation.
To achieve these goals, present invention employs following technical scheme:
The invention provides a kind of crystal formation x2 of ethinyloestradiol, in the x- ray powder diffraction pattern of described crystal formation x2 in 2 θ it is
8.022°±0.2°、10.765°±0.2°、11.879°±0.2°、13.133°±0.2°、13.791°±0.2°、16.305°
There is characteristic peak at ± 0.2 ° of position.
Further, described crystal formation x2 has and consists essentially of characteristic x- ray powder diffraction peak shown below:
The angle of diffraction 2 θ be respectively as follows: 5.349 ° ± 0.2 °, 7.677 ° ± 0.2 °, 8.022 ° ± 0.2 °, 10.765 ° ± 0.2 °,
11.879°±0.2°、13.133°±0.2°、13.791°±0.2°、14.644°±0.2°、15.049°±0.2°、15.448°
±0.2°、16.305°±0.2°、17.218°±0.2°、18.054°±0.2°、19.605°±0.2°、20.636°±0.2°、
22.033°±0.2°、22.43°±0.2°、23.662°±0.2°、24.592°±0.2°;Corresponding crystal face square d is respectively as follows:
Further, described crystal formation x2 has the x- ray powder diffraction pattern substantially the same with accompanying drawing Fig. 1.
" substantially the same x- ray powder diffraction pattern " refers at least 80% in x- ray powder diffraction pattern, or at least
90%, or at least 95%, or at least 99% peak is shown in figure.
Further, the infrared spectrum of described crystal formation x2 has absorption band: 3409cm about values below-1±2cm-1、3291cm-1±2cm-1、3051cm-1±2cm-1、3027cm-1±2cm-1、2976cm-1±2cm-1、2937cm-1±2cm-1、2865cm-1±
2cm-1、2529cm-1±2cm-1、2221cm-1±2cm-1、2108cm-1±2cm-1、1863cm-1±2cm-1、1742cm-1±2cm-1、1720cm-1±2cm-1、1687cm-1±2cm-1、1617cm-1±2cm-1、1586cm-1±2cm-1、1498cm-1±2cm-1、
1449cm-1±2cm-1、1375cm-1±2cm-1、1358cm-1±2cm-1、1319cm-1±2cm-1、1286cm-1±2cm-1、
1249cm-1±2cm-1、1180cm-1±2cm-1、1156cm-1±2cm-1、1144cm-1±2cm-1、1134cm-1±2cm-1、
1114cm-1±2cm-1、1079cm-1±2cm-1、1060cm-1±2cm-1、1018cm-1±2cm-1、971cm-1±2cm-1、
931cm-1±2cm-1、913cm-1±2cm-1、871cm-1±2cm-1、845cm-1±2cm-1、819cm-1±2cm-1、786cm-1±
2cm-1、734cm-1±2cm-1There is infrared spectrum characteristic peak in place.
In the dsc analysis of described crystal formation x2, there is heat absorption at 100.7 DEG C ± 3 DEG C, 147.0 DEG C ± 3 DEG C, 184.8 DEG C ± 3 DEG C
Peak.
In the tg analysis of described crystal formation x2, being heated to weightless when 130 DEG C is 12.5%.
Known obtain x-ray powder diffraction spectrum, it has according to measuring condition (such as device therefor or machine)
One or more measure errors.Especially, the intensity of commonly known x-ray powder diffraction spectrum may be according to the difference of measuring condition
And fluctuate.Thus, it will be appreciated that the crystal formation x2 of the present invention be not limited to provide consistent with x-ray powder diffraction spectrum shown in the drawings
The crystal formation of x-ray powder diffraction spectrum, any crystal formation with those substantially identical x-ray powder diffraction spectrums shown in the drawings
Also within the scope of the present invention.The technical staff in x-ray powder diffraction field can interpolate that the essence of x-ray powder diffraction spectrum
Uniformity.
The invention provides a kind of preparation method of foregoing crystal formation x2, described preparation method comprises the steps:
By the ethinyloestradiol for 400:1 for the mass volume ratio and dioxane mixing, being slowly dropped into dioxane volume ratio is 4:1-10:1
Hexamethylene, stirring separate out solid.
Preferably, described preparation method comprises the steps: the ethinyloestradiol for 400:1 for the mass volume ratio and dioxane
Mixing, being slowly dropped into dioxane volume ratio is the hexamethylene of 8:1, and stirring separates out solid.
In the specific embodiment of the present invention, the invention provides a kind of preparation method of foregoing crystal formation x2,
Described preparation method comprises the steps: about 200mg ethinyloestradiol is dissolved in 0.5ml dioxane, and solution is slowly dropped into 4ml
In hexamethylene, stirring separates out solid.
Present invention also offers a kind of pharmaceutical composition, described pharmaceutical composition includes the foregoing of therapeutically effective amount
Crystal formation x2.
Term as used herein, " therapeutically effective amount " refers to the amount of compound, when for treat a kind of disease, or a kind of disease or
Uncomfortable at least one clinical symptoms and to an individual be administered when, enough for affecting controlling of these diseases, discomfort or symptom
Therapeutic effect.Described " therapeutically effective amount " can be according to the symptom of compound, disease, discomfort and/or disease or discomfort, disease, no
The seriousness of the symptom of suitable and/or disease or discomfort, treat the individual age, and/or is treated individual weight and become
Change.Suitable amount in any specific example is obvious to those skilled in the art, or can be by conventional real
Test to determine.In the case of composite treatment, term " therapeutically effective amount " refers to effectively treatment disease, the composition of discomfort or situation
Total amount.
Further, described pharmaceutical composition also includes pharmaceutically acceptable carrier.
Described " pharmaceutically acceptable carrier " refers to be suitable to the pharmaceutical carrier of the routine of pharmaceutical dosage form of requirement, for example: dilute
Release agent, communication media such as water, various organic solvents, etc.;Filler such as starch, sucrose, etc.;Binder such as cellulose
Derivative, alginates, gelatin and polyvinylpyrrolidone (pvp);Wetting agent such as glycerine;Disintegrant such as agar, calcium carbonate,
Sodium acid carbonate;Sorbefacient, such as quarternary ammonium salt compound;Surfactant such as hexadecanol;Adsorbent such as kaolin and soap
Soil;Lubricant such as mica, calcium stearate, magnesium stearate, polyethylene glycol, etc..In addition, described pharmaceutical composition is wrapped further
Include other medicines acceptable excipient such as dispersant, stabilizer, thickener, complexing agent, buffer, penetration enhancer, height
Molecule, aromatic, sweetener, and coloring agent.Preferably, described excipient is suitable for formulation and the administering mode of requirement.
The pharmaceutical composition of compound of the present invention can be sucked, rectum by oral, and injection or local are administered to needing
Individual administration to be treated.For Oral administration, described pharmaceutical composition can be conventional solid dosage forms, such as medicine
Piece, powder, little particle, capsule etc., liquid dosage form such as water or oil suspension or other liquid dosage form such as syrup, solution,
Suspension etc.;For drug administration by injection mode, described pharmaceutical composition can be solution, the aqueous solution, oil-based suspension concentrates,
Freeze-dried powder etc..
Preferably, the formulation of described pharmaceutical composition is selected from tablet, coated tablet, capsule, suppository, nasal spray or injection
Agent, more preferably tablet or capsule.Described pharmaceutical composition can be to have the individual unit administration of exact dose.
Whole formulations of pharmaceutical composition of the present invention can be prepared by the conventional method of drug world.
" crystal formation " refers to the ordered arrangement of uniqueness and/or the conformation of molecule in lattice for the compound in the present invention.
In the present invention, 2 θ values in x- ray powder diffraction pattern are all to spend (°) as unit.
When refer to spectrogram or/and occur in figure data when, what " peak " referred to that those skilled in the art are capable of identify that will not
Belong to a feature of background noise.
In general, x- ray powder diffraction peak, 2 θ of its x- ray powder diffraction or the diffraction maximum of described crystal formation
Measured experimental error, between a machine and another machine and between a sample and another sample, x- penetrates
2 θ of line powder diffraction spectrum or diffraction maximum measure may slightly difference, the numerical value of described experimental error or difference is probably
About 0.2 unit of +/-, about 0.1 unit of +/- or about 0.05 unit of +/-, the numerical value of therefore described 2 θ or diffraction maximum
Can not be considered as absolute.
In the context of the present invention, when using or regardless of whether when using the wording such as " about " or " about ", represent every
One digital numerical value is possible to 1%, 2%, 5%, 7%, 8% or 10% difference occurs.
Advantages of the present invention and beneficial effect:
The crystal formation x2 of the present invention has stability height, the pharmaceutical composition stability made by the crystal formation x2 of the present invention
Height, long shelf-life, and be suitable for being transported under extreme weather and storing.
Brief description
Fig. 1 shows the x- ray powder diffraction pattern of ethinyloestradiol crystal formation x2;
Fig. 2 shows the dsc figure of ethinyloestradiol crystal formation x2;
Fig. 3 shows the ir figure of ethinyloestradiol crystal formation x2;
Fig. 4 shows the tg figure of ethinyloestradiol crystal formation x2.
Specific embodiment
Further illustrate the present invention below by specific embodiment it should be noted that such as no particularly pointing out, the enforcement of the present invention
Example is only used for explaining the present invention, is not meant to limit protection scope of the present invention.
The preparation of embodiment 1 ethinyloestradiol crystal formation x2
About 200mg ethinyloestradiol is dissolved in 0.5ml dioxane, solution is slowly dropped in 4ml hexamethylene, stirring separates out
Solid.
The preparation of embodiment 2 ethinyloestradiol crystal formation x2
About 200mg ethinyloestradiol is dissolved in 0.5ml dioxane, solution is slowly dropped in 2ml hexamethylene, stirring separates out
Solid.
The preparation of embodiment 3 ethinyloestradiol crystal formation x2
About 200mg ethinyloestradiol is dissolved in 0.5ml dioxane, solution is slowly dropped in 5ml hexamethylene, stirring separates out
Solid.
The sign of embodiment 4 ethinyloestradiol crystal formation x2
1st, x- ray powder diffraction detection
Preparation of samples: crystal form samples are ground and cross 100 mesh sieves, and precision weighing 50mg is as diffraction experiment sample.
Using instrument: Japanese rigaku company (d/max-2550) is detected.
Experiment condition: cuk α radiation, graphite monochromator, pipe presses 3~80 ° of θ sweep limits of 40kv, pipe stream 150ma, 2, scanning
Speed 8 °/point, 0.02 ° of step-length, 1 ° of ds transmite slit, 1 ° of ss antiscatter slits, it is 0.15mm that rs receives slit.
Result: the x- ray powder diffraction of ethinyloestradiol crystal formation x2 is as shown in figure 1, design parameter is as shown in table 2:
Table 2 ethinyloestradiol crystal formation x2 diffraction maximum parameter
2nd, ir detection
Preparation of samples: crystal form samples are ground and cross 100 mesh sieves, kbr compressing tablet, carry out infrared detection.
Using instrument: perkinelmer company of the U.S. produces (spectrum 400).
Experiment condition: spectral scanning range 4000-650cm-1, resolution ratio 4.000cm-1, scanning times 16 times, using declining
Subtract total reflection technology (atr) and measure infrared absorption spectroscopy.
Result: the infrared spectrum of described crystal formation x2 has absorption band: 3409cm about values below-1、3291cm-1、3051cm-1、3027cm-1、2976cm-1、2937cm-1、2865cm-1、2529cm-1、2221cm-1、2108cm-1、1863cm-1、1742cm-1、
1720cm-1、1687cm-1、1617cm-1、1586cm-1、1498cm-1、1449cm-1、1375cm-1、1358cm-1、1319cm-1、
1286cm-1、1249cm-1、1180cm-1、1156cm-1、1144cm-1、1134cm-1、1114cm-1、1079cm-1、1060cm-1、
1018cm-1、971cm-1、931cm-1、913cm-1、871cm-1、845cm-1、819cm-1、786cm-1、734cm-1Place exists infrared
Spectral signature peak, the tolerance of its middle infrared spectrum characteristic peak is ± 2cm-1.
3rd, tg detection
Preparation of samples: crystal form samples are ground and cross 100 mesh sieves, and precision weighs 2~4mg sample, detection.
Using instrument: mettler toledo company of Switzerland produces (tga/dsc-1).
Experiment condition: alumina crucible, temperature range: 30~500 DEG C, heating rate: 10k/min, nitrogen flow rate:
50ml/ divides, and weighs 4~10mg sample and is detected.
Result: in the tg analysis of described crystal formation x2, being heated to weightless when 130 DEG C is 12.5%.
4th, dsc detection
Preparation of samples: crystal form samples are ground and cross 100 mesh sieves, and precision weighs 2~4mg sample, detection.
Using instrument: mettler toledo company of Switzerland produces (dsc-1 500).
Experiment condition: aluminium crucible, heating rate is 10k/min, and calefactive interzone is 30~200 DEG C.
Result: in the dsc analysis of described crystal formation x2, have at 100.7 DEG C ± 3 DEG C, 147.0 DEG C ± 3 DEG C, 184.8 DEG C ± 3 DEG C
Endothermic peak.
The explanation of above-described embodiment is only intended to understand the method for the present invention and its core concept.It should be pointed out that for this
For the those of ordinary skill in field, under the premise without departing from the principles of the invention, some improvement can also be carried out to the present invention
And modification, these improve and modify also by the protection domain falling into the claims in the present invention.
Claims (10)
1. a kind of crystal formation x2 of ethinyloestradiol is it is characterised in that in the x- ray powder diffraction pattern of described crystal formation x2 in 2 θ be
8.022°±0.2°、10.765°±0.2°、11.879°±0.2°、13.133°±0.2°、13.791°±0.2°、16.305°
There is characteristic peak, described crystal formation x2 is the crystal formation of the ethinyloestradiol hydrate containing 2.5 hydrones at ± 0.2 ° of position.
2. crystal formation x2 according to claim 1 is it is characterised in that described crystal formation x2 consists essentially of feature shown below
Property x- ray powder diffraction peak:
The angle of diffraction 2 θ be respectively as follows: 5.349 ° ± 0.2 °, 7.677 ° ± 0.2 °, 8.022 ° ± 0.2 °, 10.765 ° ± 0.2 °,
11.879°±0.2°、13.133°±0.2°、13.791°±0.2°、14.644°±0.2°、15.049°±0.2°、15.448°
±0.2°、16.305°±0.2°、17.218°±0.2°、18.054°±0.2°、19.605°±0.2°、20.636°±0.2°、
22.033°±0.2°、22.43°±0.2°、23.662°±0.2°、24.592°±0.2°;Corresponding crystal face square d is respectively as follows:
3. crystal formation x2 according to claim 1 and 2 it is characterised in that described crystal formation x2 have substantially the same with Fig. 1
X- ray powder diffraction pattern.
4. crystal formation x2 according to claim 1 is it is characterised in that the infrared spectrum of described crystal formation x2 is in 3409cm-1±
2cm-1、3291cm-1±2cm-1、3051cm-1±2cm-1、3027cm-1±2cm-1、2976cm-1±2cm-1、2937cm-1±2cm-1、2865cm-1±2cm-1、2529cm-1±2cm-1、2221cm-1±2cm-1、2108cm-1±2cm-1、1863cm-1±2cm-1、
1742cm-1±2cm-1、1720cm-1±2cm-1、1687cm-1±2cm-1、1617cm-1±2cm-1、1586cm-1±2cm-1、
1498cm-1±2cm-1、1449cm-1±2cm-1、1375cm-1±2cm-1、1358cm-1±2cm-1、1319cm-1±2cm-1、
1286cm-1±2cm-1、1249cm-1±2cm-1、1180cm-1±2cm-1、1156cm-1±2cm-1、1144cm-1±2cm-1、
1134cm-1±2cm-1、1114cm-1±2cm-1、1079cm-1±2cm-1、1060cm-1±2cm-1、1018cm-1±2cm-1、
971cm-1±2cm-1、931cm-1±2cm-1、913cm-1±2cm-1、871cm-1±2cm-1、845cm-1±2cm-1、819cm-1±
2cm-1、786cm-1±2cm-1、734cm-1±2cm-1There is infrared spectrum characteristic peak in place.
5. crystal formation x2 according to claim 1 it is characterised in that described crystal formation x2 dsc analysis in, at 100.7 DEG C ± 3
DEG C, 147.0 DEG C ± 3 DEG C, 184.8 DEG C ± 3 DEG C have endothermic peak.
6. a kind of preparation method of the crystal formation x2 any one of claim 1-5 is it is characterised in that described preparation method bag
Include following steps: the mifepristone for 400:1 for the mass volume ratio and dioxane mixing are slowly dropped into and dioxane volume
The hexamethylene for 4:1-10:1 for the ratio, stirring separates out solid.
7. preparation method according to claim 6 is it is characterised in that described preparation method comprises the steps: quality
Volume ratio is mifepristone and the dioxane mixing of 400:1, and being slowly dropped into dioxane volume ratio is the hexamethylene of 8:1,
Stirring separates out solid.
8. preparation method according to claim 7 is it is characterised in that described preparation method comprises the steps: about
200mg ethinyloestradiol is dissolved in 0.5ml dioxane, and solution is slowly dropped in 4ml hexamethylene, and stirring separates out solid.
9. a kind of pharmaceutical composition is it is characterised in that described pharmaceutical composition includes appointing in claim 1-5 of therapeutically effective amount
Crystal formation x2 described in one.
10. pharmaceutical composition according to claim 9 is it is characterised in that described pharmaceutical composition also includes pharmaceutically may be used
The carrier accepting.
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108794555A (en) * | 2018-04-26 | 2018-11-13 | 国家卫生计生委科学技术研究所 | A kind of ethinyloestradiol pharmaceutical co-crystals and preparation method thereof |
CN111662354A (en) * | 2019-03-05 | 2020-09-15 | 中国医学科学院药物研究所 | Mifepristone crystal N-type solid matter, preparation method, pharmaceutical composition and application thereof |
CN111662355A (en) * | 2019-03-05 | 2020-09-15 | 中国医学科学院药物研究所 | Mifepristone crystal W-type solid matter, preparation method, pharmaceutical composition and application thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101198332A (en) * | 2005-05-13 | 2008-06-11 | 拜耳先灵医药股份有限公司 | Pharmaceutical composition comprising progestogens and/or estrogens and 5-methyl- (6S)-tetrahydrofolate |
CN101484143A (en) * | 2006-07-06 | 2009-07-15 | 拜耳先灵医药股份有限公司 | Pharmaceutical composition containing a tetrahydrofolic acid |
-
2016
- 2016-08-23 CN CN201610709151.3A patent/CN106336444A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101198332A (en) * | 2005-05-13 | 2008-06-11 | 拜耳先灵医药股份有限公司 | Pharmaceutical composition comprising progestogens and/or estrogens and 5-methyl- (6S)-tetrahydrofolate |
CN101484143A (en) * | 2006-07-06 | 2009-07-15 | 拜耳先灵医药股份有限公司 | Pharmaceutical composition containing a tetrahydrofolic acid |
Non-Patent Citations (1)
Title |
---|
C. GUGUTA等: "Structural Diversity of Ethinyl Estradiol Solvates", 《CRYSTAL GROWTH & DESIGN 》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108794555A (en) * | 2018-04-26 | 2018-11-13 | 国家卫生计生委科学技术研究所 | A kind of ethinyloestradiol pharmaceutical co-crystals and preparation method thereof |
CN111662354A (en) * | 2019-03-05 | 2020-09-15 | 中国医学科学院药物研究所 | Mifepristone crystal N-type solid matter, preparation method, pharmaceutical composition and application thereof |
CN111662355A (en) * | 2019-03-05 | 2020-09-15 | 中国医学科学院药物研究所 | Mifepristone crystal W-type solid matter, preparation method, pharmaceutical composition and application thereof |
CN111662354B (en) * | 2019-03-05 | 2023-03-24 | 中国医学科学院药物研究所 | Mifepristone crystal N-type solid matter, preparation method, pharmaceutical composition and application thereof |
CN111662355B (en) * | 2019-03-05 | 2023-03-24 | 中国医学科学院药物研究所 | Mifepristone crystal W-type solid matter, preparation method, pharmaceutical composition and application thereof |
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