CN104945364A - Icaritin compound and application of compound - Google Patents
Icaritin compound and application of compound Download PDFInfo
- Publication number
- CN104945364A CN104945364A CN201510419782.7A CN201510419782A CN104945364A CN 104945364 A CN104945364 A CN 104945364A CN 201510419782 A CN201510419782 A CN 201510419782A CN 104945364 A CN104945364 A CN 104945364A
- Authority
- CN
- China
- Prior art keywords
- compound
- kela
- crystal formation
- cancer
- place
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
-
- 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
Abstract
The invention provides an icaritin compound which is a hydrate of icaritin. Crystallization preparation speed is high, the crystallization technology is simple, and the yield of the crystallization process can reach 95%. Thus, wide prospects are provided for further utilization of icaritin.
Description
Technical field
The present invention relates to the purposes that a kind of A Kela determines compound, this compound, belong to field of medicaments.
Background technology
A Kelading, has another name called Icaritin, epimedium aglucone, and be the new effective monomer that extraction and isolation obtains from Chinese medicinal materials Herba Epimedii main active ingredient Herba Epimedii extract obtains through enzymatic conversion, its structural formula is as shown in the formula shown in (A):
Disclose " Icaritin is on the impact of estrogen-dependent breast cancer MCF-7 cytosis " " the Chinese experimental pharmacology of traditional Chinese medical formulae " the 18th volume 14 in 2012 is interim, and disclose by research the proliferation function that Icaritin and estradiol combined action have the MCF-7 Human Breast Cancer Cells suppressing E2 to induce.
Disclose the article of " Icaritin In Vitro Anti lymphoma cell multiplication effect " in " Chinese comparative medicine magazine " the 6th phase in 2011, and this article disclose the effect of Icaritin to tumor cell proliferation.
Be the preparation method disclosing Icaritin in the Chinese patent of 200710099025.1 in the patent No., the method carries out enzyme digestion reaction by beta-glucosidase to icarin, carries out the sterling that recrystallization obtains Icaritin after enzyme digestion reaction by acetone-water.
Be disclose the crystal formation that a kind of A Kela determines compound in the Chinese patent application of 201410185323.2 at application number, this crystal formation is a kind of solvent-free crystal formation.
But present inventor is found by test of many times, A Kela also also exists the aquo compound of stable in properties surely, and therefore, the further utilization fixed for A Kela provides wide prospect.
Summary of the invention
An object of the present invention is to provide a kind of A Kela and determine compound.
Another object of the present invention is to provide A Kela of the present invention and determines the purposes of compound in the medicine for the preparation for the treatment of abnormal cell proliferation diseases related.
One aspect of the present invention provides a kind of A Kela and determines compound,
Wherein, X is 0.5 or 1.
Preferably, as X=0.5, described compound is that A Kela determines semihydrate, and the X-ray powder diffraction that its crystal formation uses Cu-Ka radionetric survey to obtain is 4.9 at 2 θ
0± 0.2
0, 5.9
0± 0.2
0with 25.3
0± 0.2
0place goes out peak.
Preferably, the crystal formation of described compound is also 9.2
0± 0.2
0, 9.9
0± 0.2
0with 12.4
0± 0.2
0place goes out peak.
Preferably, the crystal formation of described compound is also 15.4
0± 0.2
0, 16.6
0± 0.2
0with 22.7
0± 0.2
0place goes out peak.
Preferably, the crystal formation of described compound is also 18.2
0± 0.2
0, 18.8
0± 0.2
0, 20.1
0± 0.2
0with 21.3
0± 0.2
0place goes out peak.
Preferably, as X=1, described compound is that A Kela determines monohydrate, and the X-ray powder diffraction that its crystal formation uses Cu-Ka radionetric survey to obtain is 5.1 at 2 θ
0± 0.2
0, 6.1
0± 0.2
0with 10.1
0± 0.2
0place goes out peak.
Preferably, the crystal formation of this compound is also 7.8
0± 0.2
0, 9.4
0± 0.2
0, 12.6
0± 0.2
0with 16.8
0± 0.2
0place goes out peak.
Preferably, the crystal formation of this compound is also 15.6
0± 0.2
0, 20.2
0± 0.2
0, 21.5
0± 0.2
0with 25.5
0± 0.2
0place goes out peak.
Further aspect of the present invention additionally provides the purposes of the compounds of this invention in the medicine for the preparation of anti-cell abnormality proliferation diseases related.
Preferably, the relevant disease of described abnormal cell proliferation is malignant tumour or reproducibility aplastic anemia.
Preferably, described malignant tumour comprises mammary cancer, cervical cancer, ovarian cancer, colorectal carcinoma, carcinoma of endometrium, liver cancer, lung cancer, bone marrow cancer, prostate cancer or cancer of the stomach.
Beneficial effect of the present invention is: it is the fixed hydrate of A Kela that the A Kela in the present invention determines compound, and hydrate crystal forms is compared with solvent-free crystal formation, and it is fast that hydrate crystal forms of the present invention prepares speed, and crystallisation process only needs 10 minutes.And solvent-free crystal formation crystallization rate is slow, general needs more than 24 hours.Therefore, the production efficiency of solvent-free crystal-form compound contains crystal compound far below of the present invention.
Hydrate crystal forms preparation process operation of the present invention is simpler, and operating process controls without the need to strict temperature.Only need under agitation, acetone soln fixed for A Kela is added to the water fast and forms semihydrate crystal formation; Or water added in the fixed acetone soln of A Kela fast form monohydrate crystal form.And in the preparation process of solvent-free crystal formation, need under reflux, be first surely dissolved in by A Kela in the double solvents of acetone and water, then strict controlled cooling model temperature could the good crystal formation of acquired character.
In addition, it is 90-95% that A Kela determines hydrate crystal forms at the yield of preparation process, and the yield of solvent-free crystal-form compound preparation process is 75-85%.Under the condition that acetone consumption is identical, hydration crystal formation is in preparation process, and the volumetric usage of purified water is 4-20 times of acetone; And solvent-free crystal formation is in preparation process, the volumetric usage of purified water is 0.5-2 times of acetone.Under 40 DEG C of conditions, because A Kela can dissolve in acetone surely, water insoluble, therefore for the crystalline mother solution that water and acetone mixing solutions form, hydration crystal-form compound is less than solvent-free crystal-form compound the residual of crystalline mother solution.Therefore, the yield of hydration crystal formation is higher than solvent-free crystal formation.
A Kela of the present invention determines hydrate crystal forms and A Kela, and to determine anhydrous crystal forms the same, also has good storage stability.
In addition, the light stability that A Kela of the present invention determines hydration crystal formation is better than the light stability of anhydrous crystal forms, therefore, uses the fixed moisture crystal formation of A Kela by minimizing illumination to the impact of drug storage, extends the validity period of medicine.
Accompanying drawing explanation
Fig. 1 represents that A Kela prepared by embodiment 1 method determines the nmr spectrum of semihydrate crystal formation.
Fig. 2 represents that A Kela prepared by embodiment 1 method determines the nmr spectrum of anhydrous crystal forms.
Fig. 3 represents that A Kela prepared by embodiment 1 method determines thermogravimetric analysis and the differential scanning calorimetry curve of hemi-hydrate crystalline.
Fig. 4 represents the X-ray powder diffraction pattern of embodiment 1 A Kelading hemi-hydrate crystalline.
Fig. 5 represents that A Kela of the present invention determines the thermal gravimetric analysis curve of monohydrate crystal.
Fig. 6 represents that A Kela of the present invention determines the X-ray powder diffraction pattern of monohydrate crystal.
Fig. 7 represents that A Kela determines anhydrous crystal forms through the HPLC collection of illustrative plates of illumination after 5 days.
Fig. 8 represents that the fixed semi-crystal type of A Kela is through the HPLC collection of illustrative plates of illumination after 5 days.
Fig. 9 represents that the fixed hydration crystal formation in Accra is through the HPLC collection of illustrative plates of illumination after 5 days.
Embodiment
Unless otherwise indicated, term " A Kela determines semihydrate " herein refers to the aquo compound that and half molecular water fixed by a part A Kela forms.
Unless otherwise indicated, term " A Kela determines monohydrate " herein refers to the aquo compound that and a part water fixed by a part A Kela forms.
Unless otherwise indicated, term " solvent-free crystal formation " herein refers to A Kela and to determine in compound not containing water or other solvent, the specific crystal formation formed by compound molecule or the special lattice vacancy arrangement of atom.
Unless otherwise indicated, term " abnormal cell proliferation " herein refers to the growth of cell, differentiation and apoptosis and departs from the normal growth cycle of cell.
Unless otherwise indicated, term " disease that anti-cell abnormality proliferation is relevant " herein refers to treatment or the prevention disease relevant with abnormal cell proliferation.
Unless otherwise indicated, term " thermogravimetric analysis " herein refers to a kind of thermoanalysis technology measuring relation between the quality of testing sample and temperature variation under programed temperature.
Unless otherwise indicated, term " differential scanning calorimetry " herein refers under the condition of temperature variation, measures thing relative to reference substance in the temperature variant a kind of analytical technology of the energy difference of unit time.
Embodiment
Embodiment 1
Be purchased Herba Epimedii extract enzymolysis process and prepare A Kela calmly
Herba Epimedii extract in the present embodiment is purchased from Jiahe, Shaanxi plant Chemical Co., Ltd., and trade name is " Herba Epimedii extract ", and wherein containing massfraction is the icarin of 90%.
Step one: it is fixed that enzymolysis process prepares A Kela
By the 80g Herba Epimedii extract be purchased, wherein containing massfraction is the icarin of 90%, be scattered in Sodium phosphate dibasic-potassium phosphate buffer 2.0L that concentration is the pH5.2 of 1mol/L, add ethanol 0.6L, RAPIDASE polygalacturonase 1400g, amount to 1.4L in 5L reactor.Wherein, " polygalacturonase " is the polygalacturonase of RAPIDASE purchased from the trade mark of DSM company, and production code member is 984.
Temperature of reaction carries out enzymolysis under the condition of 50 DEG C, and concrete condition is as table 1:
Table 1 enzymatic hydrolysis condition
| Herba Epimedii extract g | Enzyme amount L | Ethanol L | Damping fluid L | Temperature of reaction |
| 80 | 1.4 | 0.6 | 2.0 | 50℃ |
Detected by HPLC, reaction system transforms 70 hours, and it is fixed that icarin is converted into A Kela, and transformation efficiency reaches 90%.The purity fixed due to the A Kela obtained is inadequate, needs to purify further.
The preparation of the fixed half hydration crystal formation of step 2: A Kela
Get the Partial digestion product that step one obtains and carry out purifying.Get 10.0g enzymolysis product, 700mL acetone in 1L beaker, stirring and dissolving in warm water bath.Then acetone soln fixed for A Kela is joined fast in the flask of the purified water that 4L normal temperature is housed, vigorous stirring 10min, now separate out a large amount of yellow solid.Be down to after room temperature until solution and filter, filter cake is placed in 25 DEG C of air dry ovens dry 48 hours, obtains yellow powder 9.2g, yield 92%.Sample presentation carry out nuclear magnetic resonance spectroscopy (
1h NMR), obtain collection of illustrative plates as shown in Figure 1; Thermogravimetric analysis and differential scanning calorimetry (TGA/DSC), obtain collection of illustrative plates as shown in Figure 3; Powder diffraction analysis (XRPD) collection of illustrative plates as shown in Figure 4.
By the comparison of Fig. 1 and Fig. 2, can find out that nmr spectrum that A Kela prepared by embodiment 1 method determines semihydrate crystal formation and the fixed solvent-free crystal formation of Fig. 2 A Kela goes out peak position and do not change.In addition, go out peak at Fig. 1 displacement 2.1ppm place, this peak is the hydrogen peak of acetone, because the mass content of acetone in sample is 0.2%, illustrates in this sample not containing acetone solvent.
Visible by the thermogravimetric analysis figure of Fig. 3, weightless when sample is heated to 80 DEG C is 3.0% of example weight, differential scanning calorimetry figure is presented at when starting temperature is 60.3 DEG C and occurs desolventizing endotherm(ic)peak, there is melting endotherm(ic)peak at 253.6 DEG C, and fusion enthalpy is 120.32J/g.Shown in conjunction with 1H NMR figure by differential scanning calorimetry and thermogravimetric analysis figure, product is a kind of hydration crystal formation, and by calculating, this hydration crystal formation is the fixed semihydrate of A Kela.
Fig. 4 represents that A Kela determines the X-ray powder diffraction pattern of semihydrate crystal formation, can see that semihydrate is about 4.9 at 2 θ angles from this figure
0, about 5.9
0, about 9.2
0, about 9.9
0, about 12.4
0, about 15.4
0, about 16.6
0, about 18.2
0, about 18.8
0, about 20.1
0, about 20.8
0, about 21.3
0, about 22.7
0, about 25.3
0about 26.4
0place goes out peak.
Embodiment 2
Get the Partial digestion product that step one obtains and carry out purifying.Get 10.0g enzymolysis product, 700mL acetone in 5.0L flask, stirring and dissolving in warm water bath.Then under agitation add 4L purified water fast, continue to stir 10min.Now separate out a large amount of yellow solid, be down to after room temperature until solution and filter.Filter cake is placed in 25 DEG C of air dry ovens dry 48 hours, obtains yellow powder 9.5g, yield 95%.Filter cake is placed in 25 DEG C of air dry ovens dry 48 hours.Thermogravimetric analysis (TGA), obtains collection of illustrative plates as shown in Figure 5; Powder diffraction analysis (XRPD) collection of illustrative plates as shown in Figure 6.
Weightless when being heated to 80 DEG C by Fig. 5 thermogravimetric analysis figure show sample is 4.6% of sample gross weight.By calculating, the hydration crystal formation obtaining the present embodiment is that A Kela determines monohydrate crystal form.
Visible by X-ray powder diffraction, A Kela determines monohydrate crystal form about 5.1
0, about 6.1
0, about 7.8
0, about 9.4
0, about 10.1
0, about 12.6
0, about 15.6
0, about 16.8
0, about 20.2
0, about 21.5
0about 25.5
0place goes out peak.
Comparative example
Undertaken centrifugal by the enzymolysis product 10g that embodiment 1 step one prepares, remove supernatant, precipitation uses 2L acetone solution, filters, then in filtrate, adds about 1L distilled water, and 75 DEG C of backflows are dissolved, and places crystallization for 20 DEG C.Crystallization is after 24 hours, filters and obtains light yellow crystal, and 60 DEG C of forced air dryings 48 hours, until the weight of crystal no longer changes, obtain the anhydrous crystal forms that A Kela is fixed.Anhydrous crystal forms totally 8.1 grams, relative to enzymolysis product, yield is 81%.
Embodiment 3
The evaluation of A Kelading hydration stability of crystal form
The fixed half hydration crystal formation of A Kela get the fixed anhydrous crystal forms of the A Kela for preparing according to comparative example method, preparing according to embodiment 1 method, the placement of weighing bottle split shed is placed in each 0.2 gram of the fixed hydration crystal formation product of the A Kela prepared according to embodiment 2 method, be that 4500 ± 500 lux illumination casees place 5 days in illuminance, then detect its related substances in sample, its HPLC-UV detection is shown in shown in Fig. 7, Fig. 8 and Fig. 9 respectively.
Evaluation of result: Fig. 7 be anhydrous crystal forms through the HPLC collection of illustrative plates of illumination after 5 days, wherein retention time is 7.6 minutes, to be 8.6 minutes and retention time be retention time that the foreign matter content of 9.3 minutes is respectively 0.13%, 0.21% and 0.76%.Fig. 8 be the fixed half hydration crystal formation of A Kela through the HPLC-UV detection of illumination after 5 days, wherein retention time be the foreign matter content of 7.6 minutes, 8.6 minutes and 9.3 minutes be respectively do not detect, 0.05% and 0.59%.Fig. 9 is that A Kela determines hydration crystal formation through the high-efficient liquid phase color collection of illustrative plates of illumination after 5 days, and wherein retention time is that the foreign matter content of 7.6 minutes, 8.8 minutes and 9.3 minutes is respectively 0.03%, 0.04% and 0.42%.From above data, the light stability of the fixed half hydration crystal formation of A Kela and a hydration crystal formation is better than A Kela and determines anhydrous crystal forms.Therefore, using the fixed moisture crystal formation of A Kela by reducing illumination to the impact of drug storage, extending the validity period of medicine.
Embodiment 4
Detect A Kela respectively and determine monohydrate crystal form and A Kela determines semihydrate crystal formation to people's Endometrial carcinoma cell line Hec1A (ATCC HTB-112
tM), to liver cancer Huh-7 cell strain (purchased from Japanese Cancer Research Bank (JCRB), Tokyo, Japan), to acute myeloid leukemia cells in children MV-4-11 (ATCC CRL-9591
tM), Breast cancer lines MDA-MB-231 (ATCC HTB-26
tM), stomach cancer cell line MGC-803 (the true Industrial Co., Ltd. in Shanghai), lung cancer cell line H460 (ATCC HTB177
tM), colon cancer cell line LS 174T (ATCC CL-188
tM), pancreas cancer cell strain PANC-1 (ATCC CRL1469
tM), ptostate cancer PC 3 cell line (ATCC CRL1435
tM), cervical cancer cell lines Hela (ATCC CCL2
tM), Ovarian Cancer Cells SKOV3 (ATCC HTB-77
tM) and the restraining effect of myeloma cell strain RPMI8226 (the true Industrial Co., Ltd. in Shanghai).Detection method is identical with detection method disclosed in 201410185323.2 patent applications.
Compared with determining anhydrate crystal formation with A Kela disclosed in 201410185323.2 patent applications, detected result shows it is not no matter that A Kela determines monohydrate crystal form or A Kela and determines the inhibiting rate of semihydrate crystal formation to tumour cell equal to determine anhydrate crystal formation with A Kela identical, without any difference, therefore visible crystal water can not affect the fixed restraining effect to tumour cell of A Kela.
Claims (10)
1. the A Kela shown in following formula I determines a compound,
It is characterized in that, X is 0.5 or 1.
2. compound according to claim 1, as X=0.5, described compound is that A Kela determines semihydrate, and the X-ray powder diffraction that its crystal formation uses Cu-Ka radionetric survey to obtain is that 4.9 ° ± 0.2 °, 5.9 ° ± 0.2 ° and 25.3 ° ± 0.2 ° place go out peak at 2 θ.
3. compound according to claim 2, is characterized in that, the crystal formation of this compound also goes out peak at 9.2 ° ± 0.2 °, 9.9 ° ± 0.2 ° and 12.4 ° ± 0.2 ° place.
4. compound according to claim 2, is characterized in that, the crystal formation of this compound also goes out peak at 15.4 ° ± 0.2 °, 16.6 ° ± 0.2 ° and 22.7 ° ± 0.2 ° place.
5. compound according to claim 2, is characterized in that, the crystal formation of this compound also goes out peak at 18.2 ° ± 0.2 °, 18.8 ° ± 0.2 °, 20.1 ° ± 0.2 ° and 21.3 ° ± 0.2 ° place.
6. compound according to claim 1, as X=1, described compound is that A Kela determines monohydrate, and the X-ray powder diffraction that its crystal formation uses Cu-Ka radionetric survey to obtain is that 5.1 ° ± 0.2 °, 6.1 ° ± 0.2 ° and 10.1 ° ± 0.2 ° place go out peak at 2 θ.
7. compound according to claim 6, the crystal formation of this compound also goes out peak at 7.8 ° ± 0.2 °, 9.4 ° ± 0.2 °, 12.6 ° ± 0.2 ° and 16.8 ° ± 0.2 ° place.
8. the compound according to claim 6 or 7, the crystal formation of this compound also goes out peak at 15.6 ° ± 0.2 °, 20.2 ° ± 0.2 °, 21.5 ° ± 0.2 ° and 25.5 ° ± 0.2 ° place.
9. the purposes of compound in the medicine for the preparation of anti-cell abnormality proliferation diseases related described in claim 1,2 and 6.
10. purposes according to claim 9, it is characterized in that, the relevant disease of described abnormal cell proliferation is malignant tumour or reproducibility aplastic anemia, preferably, described malignant tumour comprises mammary cancer, cervical cancer, ovarian cancer, colorectal carcinoma, carcinoma of endometrium, liver cancer, lung cancer, bone marrow cancer, prostate cancer or cancer of the stomach.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510419782.7A CN104945364B (en) | 2014-09-16 | 2015-07-16 | A kind of A Kela determines the purposes of compound and the compound |
| TW104130599A TWI632907B (en) | 2014-09-16 | 2015-09-16 | Icaritin compound crystal form and application thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410472018.1A CN104230870A (en) | 2014-09-16 | 2014-09-16 | Icaritin compound and application thereof |
| CN2014104720181 | 2014-09-16 | ||
| CN201510419782.7A CN104945364B (en) | 2014-09-16 | 2015-07-16 | A kind of A Kela determines the purposes of compound and the compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104945364A true CN104945364A (en) | 2015-09-30 |
| CN104945364B CN104945364B (en) | 2017-03-08 |
Family
ID=52219873
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410472018.1A Pending CN104230870A (en) | 2014-09-16 | 2014-09-16 | Icaritin compound and application thereof |
| CN201510419782.7A Active CN104945364B (en) | 2014-09-16 | 2015-07-16 | A kind of A Kela determines the purposes of compound and the compound |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410472018.1A Pending CN104230870A (en) | 2014-09-16 | 2014-09-16 | Icaritin compound and application thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (2) | CN104230870A (en) |
| TW (1) | TWI632907B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105476957B (en) * | 2014-12-18 | 2021-04-20 | 北京珅奥基医药科技有限公司 | Acoradine injection and preparation method and application thereof |
| CN110699263B (en) * | 2019-10-29 | 2021-05-11 | 浙江工业大学 | Aspergillus niger YH-6 and application thereof in improving content of icaritin in epimedium |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101200743A (en) * | 2007-12-17 | 2008-06-18 | 北京珅奥基医药科技有限公司 | Method for preparing hydrated icaritin |
| CN101302548A (en) * | 2007-05-09 | 2008-11-12 | 北京珅奥基医药科技有限公司 | Preparation of icaritin |
| CN102038673A (en) * | 2009-10-20 | 2011-05-04 | 北京盛诺基医药科技有限公司 | Application of hydroxyl benzopyrone compound for preparing medicament for treating leukemia |
| CN103936705A (en) * | 2014-05-05 | 2014-07-23 | 北京盛诺基医药科技有限公司 | Crystal form of icaritin compound, drug containing crystal form and application of crystal form |
-
2014
- 2014-09-16 CN CN201410472018.1A patent/CN104230870A/en active Pending
-
2015
- 2015-07-16 CN CN201510419782.7A patent/CN104945364B/en active Active
- 2015-09-16 TW TW104130599A patent/TWI632907B/en active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101302548A (en) * | 2007-05-09 | 2008-11-12 | 北京珅奥基医药科技有限公司 | Preparation of icaritin |
| CN101200743A (en) * | 2007-12-17 | 2008-06-18 | 北京珅奥基医药科技有限公司 | Method for preparing hydrated icaritin |
| CN102038673A (en) * | 2009-10-20 | 2011-05-04 | 北京盛诺基医药科技有限公司 | Application of hydroxyl benzopyrone compound for preparing medicament for treating leukemia |
| CN103936705A (en) * | 2014-05-05 | 2014-07-23 | 北京盛诺基医药科技有限公司 | Crystal form of icaritin compound, drug containing crystal form and application of crystal form |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201611832A (en) | 2016-04-01 |
| CN104945364B (en) | 2017-03-08 |
| TWI632907B (en) | 2018-08-21 |
| CN104230870A (en) | 2014-12-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104910149A (en) | Palbociclib preparation method | |
| CN101845026A (en) | 5-(4-chlorophenylmethyl)-4-tertiary butyl thiazole derivatives and preparation method and application thereof | |
| CN103896969A (en) | Method for synthesizing 4-methyl salicylacylhydrazone copper complex with antitumor activity | |
| CN103936705B (en) | The crystal formation of A Kelading compound, the medicine containing this crystal formation and purposes | |
| CN106986871B (en) | A kind of crystal form and its preparation method and application of deuterated Palbociclib | |
| CN101486733B (en) | Oxygen-containing bridge dinuclear molybdenum cluster compound, and preparation and use thereof | |
| CN104945364A (en) | Icaritin compound and application of compound | |
| CN108033912A (en) | Low 1,8- Naphthalamide derivatives of a kind of toxicity and its preparation method and application | |
| CN103102331B (en) | Pharmaceutical application of chalcone compound containing piperazine ring | |
| CN110396077B (en) | Preparation method of belamcanda chinensis aglycone sodium sulfonate | |
| CN111892488A (en) | Method for efficiently synthesizing 2, 6-dichloro-3-fluoro acetophenone | |
| CN103497155A (en) | (+)-4-(2,3-dihydroxypropyl)-formamide-6-azabenzanthrone, and synthetic method and application thereof | |
| CN113801107B (en) | Naringenin derivative with anti-tumor activity and preparation and application of Ni (II) complex of naringenin derivative | |
| CN103319485B (en) | 6-(beta-alkylnaphthy)mercaptopurine compound, and synthesis method and application thereof | |
| CN103044326A (en) | 5-bromo oxoisoaporphine, and synthesis method and application thereof | |
| CN101716175B (en) | New application of 3-amido-6-(4-methoxyphenyl) thiopheno[2, 3-b] pyridine-2-formamide | |
| CN113788822B (en) | Novel naringenin pyrimidine hydrazone derivative and preparation method and application thereof | |
| CN102603694B (en) | Novel synthesis method of murrayone and novel application of murrayone | |
| CN103130803B (en) | Oxidized iso-aporphine alkaloid derivative, synthetic method and application | |
| CN108084201B (en) | Oxoindolspirotetrahydrofuran skeleton material, crystal thereof and preparation method thereof | |
| CN107382941B (en) | Flavone derivative and preparation method and application thereof | |
| CN115746017A (en) | Thienopyrimidine compound and preparation method and application thereof | |
| CN107365330B (en) | Dihydromyricetin two banks mono-sodium salt derivative and its preparation method and application | |
| CN104341415B (en) | A kind of Fibrauretin acylhydrazone and its production and use | |
| CN104666311A (en) | Application of O-(triazolyl) ethyl derivative of Cleistanone in preparation of medicine resistant to acute gout |
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 | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 100086, A205, Haidian District, Beijing, 5 Patentee after: Beijing shengnuoji Pharmaceutical Technology Co., Ltd Address before: 100086, A205, Haidian District, Beijing, 5 Patentee before: Beijing Shengnuoji Medicine Technology Co., Ltd. |