CN105254572A - Crystal form, preparing method and application of Olaparib - Google Patents
Crystal form, preparing method and application of Olaparib Download PDFInfo
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- CN105254572A CN105254572A CN201510757797.4A CN201510757797A CN105254572A CN 105254572 A CN105254572 A CN 105254572A CN 201510757797 A CN201510757797 A CN 201510757797A CN 105254572 A CN105254572 A CN 105254572A
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- buddhist nun
- handkerchief buddhist
- aura handkerchief
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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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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Abstract
The invention provides a crystal form, preparing method and application of Olaparib. According to the Olaparib with the new crystal form, CuKa radiation is adopted, powder X-ray diffraction represented by 2 theta angle has diffraction peaks at 22.9+/-0.5, 23.4+/-0.5, 21.0+/-0.5, 17.1+/-0.5, 17.3+/-0.5, 14.2+/-0.5, 15.0+/-0.5, 13.5+/-0.5, 18.6+/-0.5, 20.6+/-0.5, 10.2+/-0.5, 20.3+/-0.5, 21.9+/-0.5, 25.8+/-0.5 and 26.5+/-0.5. The granularity D50 of the Olaparib with the crystal form is 2.45 microns which is quite small, so that dissolving-out speed is high when the Olaparib serves as a preparation, and drug efficacy of a product is improved. Furthermore, the preparing method is simple, and the performance of the obtained Olaparib with the crystal form is stable.
Description
Technical field
The present invention relates to crystal formation field, particularly relate to crystal formation of a kind of Aura handkerchief Buddhist nun and its preparation method and application.
Background technology
Aura handkerchief Buddhist nun, chemistry 4-[3-(4-cyclopropane carbonyl piperazine-1-carbonyl)-4-luorobenzyl]-2H-phthalazines-1-ketone by name, English Olaparib by name, structural formula is as follows:
Aura handkerchief Buddhist nun (Olaparib) is a kind of small molecules researched and developed by the KuDOS drugmaker of wholly-owned subsidiary of AstraZeneca (AstraZeneca), potent oral PARP inhibitor, it is repaired by inhibition tumor cell DNA damage, promote apoptosis of tumor cells, thus the curative effect of radiotherapy and alkylating agent and platinum-based chemotherapy can be strengthened, be mainly used in the transgenation cancer for the treatment of No. one, mastocarcinoma gene (BRCA-1), mastocarcinoma gene No. two (BRCA-2), mainly mammary cancer is present in, ovarian cancer and prostate cancer to gene.
Aura handkerchief Buddhist nun belongs to insoluble drug, usually be prepared into solid preparation administration, and for the solid preparation of crystal formation medicine, the crystal formation of the stability of preparation and dissolution rate and bulk drug has very large relation, at present, in CN101528714B, the crystal form A of the solvent-free compound of Aura handkerchief Buddhist nun is disclosed by Kudos Pharm Ltd, its X-ray powder diffraction pattern (2 θ) is at 12.0 °, 17.8 °, 21.1 °, 22.3 °, 29.2 °, 10.5 °, 14.0 °, 21.7 °, 24.3 °, 26.1 ° of existing characteristics peaks, DSC is presented at 210.1 DEG C ± 1 DEG C and there is endotherm(ic)peak, this stability of crystal form is good, but its granularity is larger, be unfavorable for Aura handkerchief Buddhist nun stripping from preparation.
Summary of the invention
In view of this, technical problem to be solved by this invention is crystal formation providing a kind of Aura handkerchief Buddhist nun and its preparation method and application, and the granularity of crystal formation Aura handkerchief Buddhist nun provided by the invention is little, and dissolution rate is fast.
The invention provides the new crystal of a kind of Aura handkerchief Buddhist nun, it is characterized in that, use CuK
αradiation, the powder x-ray diffraction represented with 2 θ angles 22.9 ± 0.5,23.4 ± 0.5,21.0 ± 0.5,17.1 ± 0.5,17.3 ± 0.5,14.2 ± 0.5,15.0 ± 0.5,13.5 ± 0.5,18.6 ± 0.5,20.6 ± 0.5,10.2 ± 0.5,20.3 ± 0.5,21.9 ± 0.5,25.8 ± 0.5,26.5 ± 0.5 have diffraction peak.
Present invention also offers the preparation method of a kind of Aura handkerchief Buddhist nun of crystal formation of the present invention, comprising:
1) Aura handkerchief Buddhist nun and solvent are refluxed, obtain Aura handkerchief Buddhist nun solution,
Described solvent is one or more in n-propyl alcohol, Virahol, propyl carbinol, isopropylcarbinol and the trimethyl carbinol;
2) filtered by Aura handkerchief Buddhist nun solution, cooling, obtains described Aura handkerchief Buddhist nun crystal formation.
Preferably, the amount ratio of described Aura handkerchief Buddhist nun and described solvent is 1g:(8 ~ 20) mL.
Preferably, naturally cooling is cooled to described in.
Preferably, described step 2) also comprise the described Aura handkerchief Buddhist nun crystal formation drying that will obtain,
The temperature of described drying is 40 ~ 70 DEG C.
Present invention also offers the mixing crystal formation of a kind of Aura handkerchief Buddhist nun, comprise the Aura handkerchief Buddhist nun of crystal formation of the present invention.
Present invention also offers a kind of medicine of Therapeutic cancer, comprise the Aura handkerchief Buddhist nun of crystal formation of the present invention or the Aura handkerchief Buddhist nun of mixing crystal formation of the present invention, and pharmaceutically acceptable vehicle.
Preferably, described cancer is mammary cancer, ovarian cancer, carcinoma of the pancreas or prostate cancer.
Preferably, the formulation of described medicine is pulvis, granule, tablet, capsule, pill, paste, sustained release preparation or controlled release preparation.
Preferably, described vehicle is one or more in wetting agent, dispersion agent, pH adjusting agent, oxidation inhibitor, weighting agent, thinner, lubricant, solubilizing agent, suspending agent, correctives, tackiness agent, disintegrating agent, osmotic pressure regulator, flocculation agent, antisticking agent, suspending agent, emulsifying agent and sanitas.
Compared with prior art, the invention provides a kind of Aura handkerchief Buddhist nun of new crystal, use CuK
αradiation, the powder x-ray diffraction represented with 2 θ angles 22.9 ± 0.5,23.4 ± 0.5,21.0 ± 0.5,17.1 ± 0.5,17.3 ± 0.5,14.2 ± 0.5,15.0 ± 0.5,13.5 ± 0.5,18.6 ± 0.5,20.6 ± 0.5,10.2 ± 0.5,20.3 ± 0.5,21.9 ± 0.5,25.8 ± 0.5,26.5 ± 0.5 have diffraction peak, and the granularity of crystal formation Aura handkerchief Buddhist nun of the present invention is D
50be 2.45 microns, granularity is less, and then when making it as preparation, dissolution rate is fast, improves the drug effect of product; And preparation method provided by the invention is simple, the crystal formation Aura handkerchief damping properties obtained also is stablized.
Accompanying drawing explanation
Fig. 1 is the x-ray diffraction pattern of the new crystal Aura handkerchief Buddhist nun that the embodiment of the present invention 1 prepares;
Fig. 2 is the DSC figure that the embodiment of the present invention 1 prepares new crystal Aura handkerchief Buddhist nun;
Fig. 3 is the X-ray powder diffraction pattern of the crystal form A Aura handkerchief Buddhist nun that comparative example 1 prepares.
Embodiment
The invention provides the new crystal of a kind of Aura handkerchief Buddhist nun, it is characterized in that, use CuK
αradiation, the powder x-ray diffraction represented with 2 θ angles 22.9 ± 0.5,23.4 ± 0.5,21.0 ± 0.5,17.1 ± 0.5,17.3 ± 0.5,14.2 ± 0.5,15.0 ± 0.5,13.5 ± 0.5,18.6 ± 0.5,20.6 ± 0.5,10.2 ± 0.5,20.3 ± 0.5,21.9 ± 0.5,25.8 ± 0.5,26.5 ± 0.5 have diffraction peak.
Concrete, the detail parameters of the X-ray diffraction of the new crystal of Aura handkerchief Buddhist nun of the present invention, in table 1, shows as diffraction peak position: 2 θ values (°); Diffraction peak relative intensity: peak height value (Height%).
The X-ray diffraction result of table 1 Aura handkerchief Buddhist nun new crystal
| Peak | 2θ(±0.5°) | Peak height value % (± 5%) |
| 1 | 22.9 | 100.0 |
| 2 | 23.4 | 46.7 |
| 3 | 21.0 | 44.3 |
| 4 | 17.1 | 33.5 |
| 5 | 17.3 | 31.6 |
| 6 | 14.2 | 29.5 |
| 7 | 15.0 | 28.1 |
| 8 | 13.5 | 27.7 |
| 9 | 18.6 | 26.6 |
| 10 | 20.6 | 19.7 |
| 11 | 10.2 | 12.3 |
| 12 | 20.3 | 10.7 |
| 13 | 21.9 | 13.9 |
| 14 | 25.8 | 10.6 |
| 15 | 26.5 | 17.9 |
Should be appreciated that, the 2 θ values of X-ray powder diffraction figure slightly can change between machine or between sample, its numerical value may differ about 0.5 unit, or differ about 0.4 unit, or differ about 0.3 unit, or differ about 0.2 unit, or differ about 0.1 unit, therefore quoted numerical value can not be interpreted as absolute value.Should be appreciated that equally, the size of peak height may differ about 5 units equally, or differ about 4 units, or differ about 3 units, or differ about 2 units, or differ about 1 unit, XRPD trace (trace) intensity be therefore included in the present invention is illustrative, and is not intended to for definitely comparing.
As preferably, the crystal formation of Aura handkerchief Buddhist nun provided by the invention, uses CuK
αradiation, the powder x-ray diffraction represented with 2 θ angles 22.9 ± 0.4,23.4 ± 0.4,21.0 ± 0.4,17.1 ± 0.4,17.3 ± 0.4,14.2 ± 0.4,15.0 ± 0.4,13.5 ± 0.4,18.6 ± 0.4,20.6 ± 0.4,10.2 ± 0.4,20.3 ± 0.4,21.9 ± 0.4,25.8 ± 0.4,26.5 ± 0.4 have diffraction peak.
As preferably, the crystal formation of Aura handkerchief Buddhist nun provided by the invention, uses CuK
αradiation, the powder x-ray diffraction represented with 2 θ angles 22.9 ± 0.3,23.4 ± 0.3,21.0 ± 0.3,17.1 ± 0.3,17.3 ± 0.3,14.2 ± 0.3,15.0 ± 0.3,13.5 ± 0.3,18.6 ± 0.3,20.6 ± 0.3,10.2 ± 0.3,20.3 ± 0.3,21.9 ± 0.3,25.8 ± 0.3,26.5 ± 0.3 have diffraction peak.
As preferably, the crystal formation of Aura handkerchief Buddhist nun provided by the invention, uses CuK
αradiation, the powder x-ray diffraction represented with 2 θ angles 22.9 ± 0.2,23.4 ± 0.2,21.0 ± 0.2,17.1 ± 0.2,17.3 ± 0.2,14.2 ± 0.2,15.0 ± 0.2,13.5 ± 0.2,18.6 ± 0.2,20.6 ± 0.2,10.2 ± 0.2,20.3 ± 0.2,21.9 ± 0.2,25.8 ± 0.2,26.5 ± 0.2 have diffraction peak.
As preferably, the crystal formation of Aura handkerchief Buddhist nun provided by the invention, uses CuK
αradiation, the powder x-ray diffraction 22.9 ± 0.1,23.4 ± 0.1 represented with 2 θ angles, 21.0 ± 0.1,17.1 ± 0.1,17.3 ± 0.1,14.2 ± 0.1,15.0 ± 0.1,13.5 ± 0.1,18.6 ± 0.1,20.6 ± 0.1,10.2 ± 0.1,20.3 ± 0.1,21.9 ± 0.1,25.8 ± 0.1,26.5 ± 0.1 have diffraction peak.
In addition, the present invention is also analyzed described new crystal by differential canning calorimetry, when using differential canning calorimetry to analyze, show as when temperature rise rate is there is 1 endotherm(ic)peak in the DSC collection of illustrative plates of per minute 10 DEG C at 175.3 DEG C ± 1 DEG C place, its spectrogram substantially as shown in Figure 2.
Should be appreciated that deviation may be had to have similar situation with X-ray powder diffraction figure numerical value, the numerical value that differential canning calorimetry is quoted can not be interpreted as absolute value.
In the present invention, Aura handkerchief Buddhist nun crystal formation the present invention prepared is defined as Aura handkerchief Buddhist nun new crystal.
Present invention also offers the preparation method of a kind of crystal formation Aura handkerchief Buddhist nun provided by the invention, comprising:
1) Aura handkerchief Buddhist nun and solvent are refluxed, obtain Aura handkerchief Buddhist nun solution,
Described solvent is one or more in n-propyl alcohol, Virahol, propyl carbinol, isopropylcarbinol and the trimethyl carbinol;
2) filtered by Aura handkerchief Buddhist nun solution, cooling, obtains the Aura handkerchief Buddhist nun of described crystal formation.
According to the present invention, Aura handkerchief Buddhist nun and solvent reflux by the present invention, obtain the saturated solution of Aura handkerchief Buddhist nun; Described solvent is preferably one or more in n-propyl alcohol, Virahol, propyl carbinol and the trimethyl carbinol; The amount ratio of described Aura handkerchief Buddhist nun and described solvent is preferably 1g:(8 ~ 20) mL, be more preferably 1g:(10 ~ 15) mL, and most preferably be 1g:(12 ~ 14) mL.
The Aura handkerchief Buddhist nun solution obtained also filters by the present invention, cooling, and drying obtains the Aura handkerchief Buddhist nun of described crystal formation; The Aura handkerchief Buddhist nun solution of heat preferably filters by described filtration, i.e. heat filtering; Described cooling is preferably naturally cooling, and the Aura handkerchief Buddhist nun solution by heat filtering naturally cools to room temperature, naturally cools to room temperature under being more preferably the Aura handkerchief Buddhist nun solution stirring by heat filtering; The present invention also comprises the Aura handkerchief Buddhist nun and separated from solvent that cooling are separated out, and the method for described separation is preferably solid filtering or centrifugation; The Aura handkerchief Buddhist nun that the present invention also comprises the crystal formation of the present invention solid-liquid separation obtained is dry, and the temperature of described drying is preferably 40 ~ 70 DEG C, is preferably 50 ~ 60 DEG C; The instrument of the present invention to drying does not have particular requirement, well known to a person skilled in the art the instrument for drying solid.
Present invention also offers the mixing crystal formation of a kind of Aura handkerchief Buddhist nun, comprise Aura handkerchief Buddhist nun crystal formation provided by the invention.
Present invention also offers a kind of medicine of Therapeutic cancer, include the Aura handkerchief Buddhist nun of effective amount crystal formation of the present invention Aura handkerchief Buddhist nun or mixing crystal formation provided by the invention, and pharmaceutically acceptable vehicle.
In the present invention, described cancer is preferably mammary cancer, ovarian cancer or prostate cancer.
In the present invention, described significant quantity refers to the pharmacologic agent dosage that can reach therapeutic action;
In the present invention, described vehicle refers to the annexation in pharmaceutical preparation except main ingredient, also can be described as auxiliary material.As the tamanori in tablet, weighting agent, disintegrating agent, lubricant, wine in medicine pill, vinegar, concoction etc., base portion in semi-solid preparation ointment, creme, sanitas in liquid preparation, oxidation inhibitor, correctives, perfume compound, solubility promoter, emulsifying agent, solubilizing agent, osmotic pressure regulator, tinting materials etc. all can be described as vehicle, specific to the present invention, preferably, vehicle of the present invention is wetting agent, dispersion agent, pH adjusting agent, oxidation inhibitor, weighting agent, thinner, lubricant, solubilizing agent, suspending agent, correctives, tackiness agent, disintegrating agent, osmotic pressure regulator, flocculation agent, antisticking agent, suspending agent, one or more in emulsifying agent and sanitas, be more preferably weighting agent, thinner, lubricant, disintegrating agent, one or more in wetting agent and tackiness agent, more preferably, weighting agent is preferably starch, Microcrystalline Cellulose, one or more in lactose and secondary calcium phosphate, described lubricant is preferably Magnesium Stearate, talcum powder or silicon-dioxide, described disintegrating agent is as one or more in dry starch, Xylo-Mucine and polyvinylpolypyrrolidone, described tackiness agent is preferably one or more in starch paste, methylcellulose gum, hydroxy propyl cellulose and gelatin.
In the present invention, the formulation of described medicine is preferably pulvis, granule, tablet, capsule, pill paste, sustained release preparation or controlled release preparation, is more preferably tablet or capsule.
The invention provides the new crystal of a kind of Aura handkerchief Buddhist nun, use CuK
αradiation, the powder x-ray diffraction represented with 2 θ angles 22.9 ± 0.5,23.4 ± 0.5,21.0 ± 0.5,17.1 ± 0.5,17.3 ± 0.5,14.2 ± 0.5,15.0 ± 0.5,13.5 ± 0.5,18.6 ± 0.5,20.6 ± 0.5,10.2 ± 0.5,20.3 ± 0.5,21.9 ± 0.5,25.8 ± 0.5,26.5 ± 0.5 have diffraction peak, and the granularity of the Aura handkerchief Buddhist nun of new crystal is D
50be 2.45 microns, granularity is less, and then when making it as preparation, dissolution rate is fast, improves the drug effect of product.
Technical scheme below in conjunction with the embodiment of the present invention is clearly and completely described, and obviously, described embodiment is only the present invention's part embodiment, instead of whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.
Embodiment 1
20.0g Aura handkerchief Buddhist nun (purity 99.1%), 200mL Virahol are added in reaction flask, be warming up to backflow, stir 30min, filtered while hot, filtrate under agitation naturally cools to room temperature crystallization, and filter, 50 DEG C of drying under reduced pressure obtain the Aura handkerchief Buddhist nun that 17.6g has new crystal, yield 88.0%, purity is 99.9%.
Carry out X-ray powder diffraction by the new crystal Aura handkerchief Buddhist nun prepared embodiment 1, the results are shown in Figure the x-ray diffraction pattern that 1, Fig. 1 is the new crystal Aura handkerchief Buddhist nun that the embodiment of the present invention 1 prepares;
Carry out differential thermal analysis by the new crystal Aura handkerchief Buddhist nun prepared embodiment 1, the results are shown in Figure 2, Fig. 2 is the DSC figure that the embodiment of the present invention 1 prepares new crystal Aura handkerchief Buddhist nun.
The stability of the new crystal Aura handkerchief Buddhist nun that embodiment 1 prepares is detected, the results are shown in Table 2, the Detection of Stability result of the new crystal Aura handkerchief Buddhist nun that 2 embodiment of the present invention 1 prepare.
The Detection of Stability result of table 2 new crystal Aura handkerchief Buddhist nun
Visible, the new crystal Aura handkerchief Buddhist nun that the present invention prepares is stable under high temperature, illumination and high humidity environment, is still stable in accelerated test.
Carry out comminution by gas stream, system pressure by the new crystal Aura handkerchief Buddhist nun obtained prepared embodiment 1: 0.8Mpa, aspiration pressure: 0.45MPa, pulverize pressure: 0.45MPa, carry out granularity Detection afterwards, result shows, its granularity (D
50) be 2.45 microns.
Comparative example 1
By adding in reaction flask in 20.0g Aura handkerchief Buddhist nun, 210mL ethanol, being warming up to backflow, stirring 30min, under stirring, naturally cooling to room temperature crystallization, filter, 70 DEG C of dry 17.6g products.
Add in reaction flask by above-mentioned product, 180mL purified water, backflow 4h, is cooled to room temperature, and filter, 70 DEG C of dried overnight, obtain the Aura handkerchief Buddhist nun that 16.8g has crystal form A, yield 84.0%, purity is 99.8%.
Carry out X-ray powder diffraction by the crystal form A Aura handkerchief Buddhist nun obtained comparative example 1, the results are shown in Figure the X-ray powder diffraction pattern that 3, Fig. 3 is the crystal form A Aura handkerchief Buddhist nun type that comparative example 1 obtains.
Carry out comminution by gas stream, system pressure by the crystal form A obtained prepared comparative example 1: 0.8Mpa, aspiration pressure: 0.45MPa, pulverize pressure: 0.45MPa, Aura handkerchief Buddhist nun carries out granularity Detection, and result shows, its granularity (D
50) be 7.63 microns.
Embodiment 2
20.0g Aura handkerchief Buddhist nun, the 300mL trimethyl carbinol are added in reaction flask, is warming up to 100 DEG C, stir 30min, filtered while hot, filtrate under agitation naturally cools to room temperature crystallization, filters, 50 DEG C of drying under reduced pressure obtain 17.9g new crystal Aura handkerchief Buddhist nun, yield 89.5%, and purity is 99.9%.
Carry out X-ray powder diffraction to the crystal formation Aura handkerchief Buddhist nun obtained, result shows, the diffraction peak position of the Aura handkerchief Buddhist nun that embodiment 2 obtains is identical with embodiment 1, is same crystal formation.
Embodiment 3
20.0g Aura handkerchief Buddhist nun, 280mL propyl carbinol add in reaction flask, are warming up to 100 DEG C, stir 30min, filtered while hot, filtrate naturally cools to room temperature crystallization under leaving standstill, and filters, 50 DEG C of drying under reduced pressure obtain 17.0g new crystal Aura handkerchief Buddhist nun, yield 85%, and purity is 99.8%.
Carry out X-ray powder diffraction to the crystal formation Aura handkerchief Buddhist nun obtained, result shows, the diffraction peak position of the Aura handkerchief Buddhist nun that embodiment 3 obtains is identical with embodiment 1, is same crystal formation.
Embodiment 4
Aura handkerchief Buddhist nun tablet
Its prescription is in table 3, and table 3 is the composition of Aura handkerchief Buddhist nun tablet and the content of each component;
The composition of table 3 Aura handkerchief Buddhist nun tablet and the content of each component
| Aura handkerchief Buddhist nun | 100mg |
| Lactose | 240mg |
| Microcrystalline Cellulose | 40mg |
| Croscarmellose sodium | 15mg |
| Lauroyl sodium sulfate | 2mg |
| Magnesium Stearate | 4mg |
Auxiliary material is identical, makes Aura handkerchief Buddhist nun be crystal form A Aura handkerchief Buddhist nun and new crystal Aura handkerchief Buddhist nun of the present invention, and preparing containing Aura handkerchief Buddhist nun is respectively the tablet of crystal form A Aura handkerchief Buddhist nun and the tablet of new crystal Aura handkerchief Buddhist nun;
To obtain containing Aura handkerchief Buddhist nun be that the tablet of crystal form A Aura handkerchief Buddhist nun and the tablet of new crystal Aura handkerchief Buddhist nun carry out dissolution rate detection, the results are shown in Table 4, table 4 is the dissolution rate detected result of the tablet of crystal form A Aura handkerchief Buddhist nun and the tablet of new crystal Aura handkerchief Buddhist nun,
The dissolution rate detected result (unit %) of the tablet of table 4 crystal form A Aura handkerchief Buddhist nun and the tablet of new crystal Aura handkerchief Buddhist nun
As can be seen from Table 4, the pharmaceutical preparation stripping containing new crystal has significant difference with the pharmaceutical preparation stripping containing crystal form A, and the drug-eluting of new crystal is faster.
The explanation of above embodiment just understands method of the present invention and core concept thereof for helping.It should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention, can also carry out some improvement and modification to the present invention, these improve and modify and also fall in the protection domain of the claims in the present invention.
Claims (10)
1. an Aura handkerchief Buddhist nun's new crystal, is characterized in that, uses CuK
αradiation, the powder x-ray diffraction represented with 2 θ angles 22.9 ± 0.5,23.4 ± 0.5,21.0 ± 0.5,17.1 ± 0.5,17.3 ± 0.5,14.2 ± 0.5,15.0 ± 0.5,13.5 ± 0.5,18.6 ± 0.5,20.6 ± 0.5,10.2 ± 0.5,20.3 ± 0.5,21.9 ± 0.5,25.8 ± 0.5,26.5 ± 0.5 have diffraction peak.
2. the Aura handkerchief Buddhist nun's of a crystal formation according to claim 1 preparation method, comprising:
1) Aura handkerchief Buddhist nun and solvent are refluxed, obtain Aura handkerchief Buddhist nun solution,
Described solvent is one or more in n-propyl alcohol, Virahol, propyl carbinol, isopropylcarbinol and the trimethyl carbinol;
2) filtered by Aura handkerchief Buddhist nun solution, cooling, obtains described Aura handkerchief Buddhist nun crystal formation.
3. preparation method according to claim 2, is characterized in that, the amount ratio of described Aura handkerchief Buddhist nun and described solvent is 1g:(8 ~ 20) mL.
4. preparation method according to claim 2, is characterized in that, described in be cooled to naturally cooling.
5. preparation method according to claim 2, is characterized in that, described step 2) also comprise the described Aura handkerchief Buddhist nun crystal formation drying that will obtain,
The temperature of described drying is 40 ~ 70 DEG C.
6. an Aura handkerchief Buddhist nun's mixing crystal formation, comprises the Aura handkerchief Buddhist nun of crystal formation according to claim 1.
7. a medicine for Therapeutic cancer, comprises the Aura handkerchief Buddhist nun of the crystal formation described in Claims 1 to 5 any one or the Aura handkerchief Buddhist nun of mixing crystal formation according to claim 6, and pharmaceutically acceptable vehicle.
8. medicine according to claim 7, is characterized in that, described cancer is mammary cancer, ovarian cancer, carcinoma of the pancreas or prostate cancer.
9. medicine according to claim 7, it is characterized in that, the formulation of described medicine is pulvis, granule, tablet, capsule, pill, paste, sustained release preparation or controlled release preparation.
10. overmedication proliferative disease medicine according to claim 7, it is characterized in that, described vehicle is one or more in wetting agent, dispersion agent, pH adjusting agent, oxidation inhibitor, weighting agent, thinner, lubricant, solubilizing agent, suspending agent, correctives, tackiness agent, disintegrating agent, osmotic pressure regulator, flocculation agent, antisticking agent, suspending agent, emulsifying agent and sanitas.
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| CN201510757797.4A CN105254572A (en) | 2015-11-09 | 2015-11-09 | Crystal form, preparing method and application of Olaparib |
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105753789A (en) * | 2015-04-17 | 2016-07-13 | 苏州晶云药物科技有限公司 | Olaparib and urea eutectic and preparation method thereof |
| CN105902512A (en) * | 2016-06-13 | 2016-08-31 | 佛山市腾瑞医药科技有限公司 | Olaparib effervescent tablet and preparation method thereof |
| CN105997911A (en) * | 2016-06-13 | 2016-10-12 | 佛山市腾瑞医药科技有限公司 | Olaparib dispersible tablets and preparation method thereof |
| CN106074409A (en) * | 2016-06-13 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of Aura handkerchief Buddhist nun's preparation and application thereof |
| WO2017153958A1 (en) * | 2016-03-11 | 2017-09-14 | Lupin Limited | Novel polymorphic forms and amorphous form of olaparib |
| CN107162985A (en) * | 2017-06-05 | 2017-09-15 | 山东裕欣药业有限公司 | A kind of olaparib compound and preparation method thereof |
| CN107266370A (en) * | 2017-08-14 | 2017-10-20 | 山东裕欣药业有限公司 | A kind of process for purification of olaparib compound |
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| CN105753789B (en) * | 2015-04-17 | 2018-09-25 | 苏州晶云药物科技有限公司 | The eutectic and preparation method thereof of olaparib and urea |
| CN105753789A (en) * | 2015-04-17 | 2016-07-13 | 苏州晶云药物科技有限公司 | Olaparib and urea eutectic and preparation method thereof |
| WO2017153958A1 (en) * | 2016-03-11 | 2017-09-14 | Lupin Limited | Novel polymorphic forms and amorphous form of olaparib |
| CN105902512A (en) * | 2016-06-13 | 2016-08-31 | 佛山市腾瑞医药科技有限公司 | Olaparib effervescent tablet and preparation method thereof |
| CN105997911A (en) * | 2016-06-13 | 2016-10-12 | 佛山市腾瑞医药科技有限公司 | Olaparib dispersible tablets and preparation method thereof |
| CN106074409A (en) * | 2016-06-13 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of Aura handkerchief Buddhist nun's preparation and application thereof |
| CN107162985A (en) * | 2017-06-05 | 2017-09-15 | 山东裕欣药业有限公司 | A kind of olaparib compound and preparation method thereof |
| CN107266370A (en) * | 2017-08-14 | 2017-10-20 | 山东裕欣药业有限公司 | A kind of process for purification of olaparib compound |
| US10662178B2 (en) | 2018-01-31 | 2020-05-26 | Apotex Inc. | Crystalline form of Olaparib |
| CN109293576A (en) * | 2018-11-08 | 2019-02-01 | 威海贯标信息科技有限公司 | A kind of preparation method of small grain size olaparib |
| CN111718300A (en) * | 2019-06-18 | 2020-09-29 | 台湾神隆股份有限公司 | Novel crystal form of olaparib and preparation method thereof |
| CN111995582A (en) * | 2020-07-09 | 2020-11-27 | 天津理工大学 | Eutectic of olaparib and urea and preparation method thereof |
| CN111995582B (en) * | 2020-07-09 | 2021-12-03 | 天津理工大学 | Eutectic of olaparib and urea and preparation method thereof |
| CN111689905A (en) * | 2020-07-22 | 2020-09-22 | 天津理工大学 | Eutectic of olaparib and maleic acid and preparation method thereof |
| CN111689905B (en) * | 2020-07-22 | 2021-12-03 | 天津理工大学 | Eutectic of olaparib and maleic acid and preparation method thereof |
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