CN106967139B - A kind of lamp-dish flower acetic crystal form and preparation method thereof - Google Patents
A kind of lamp-dish flower acetic crystal form and preparation method thereof Download PDFInfo
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/06—Benzopyran radicals
- C07H17/065—Benzo[b]pyrans
- C07H17/07—Benzo[b]pyran-4-ones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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Abstract
The invention belongs to field of pharmaceutical chemistry technology.Lamp-dish flower acetic crystal form of the present invention, is named as lamp-dish flower acetic crystal form III.It is radiated using Cu-K α, λ=1.5405A, it is 107-137 DEG C that diffraction peak intensity, which is 100%, SC analysis endothermic transition temperature, at 2 position θ 16.18 of X-ray powder diffraction, and fusion and decomposition temperature is 195-201 DEG C.Preparation method includes the following steps: one, lamp-dish flower acetic being added in organic solvent, it is completely dissolved lamp-dish flower acetic, the solution of dissolution is slowly added to again in 5-12 times of liquor capacity of aqueous solvent, and be stirred, lamp-dish flower acetic is made to be precipitated and be dispersed in aqueous solvent immediately;Two, it filters, isolates solid, be dried under reduced pressure the lamp-dish flower acetic crystal form III to get micronization.It is an advantage of the invention that improving solution rate and reducing impurity.
Description
Technical field
The invention belongs to field of pharmaceutical chemistry technology, in particular to a kind of system of new lamp-dish flower acetic crystal form and the crystal form
Preparation Method.
Background technique
Fleabane flower is that the drying of compositae plant Erigeron breviscapus Erigeron breviscapus (Vant.) Hand-Mazz is complete
Grass is distributed mainly on Yunnan Province, first recorded in " the southern regions of the Yunnan Province book on Chinese herbal medicine ", for treating the diseases such as apoplexy sequelae, rheumatism, thoracic obstruction.20 generation
(i.e. scutellarin, scutellarin, No. CAS is 27740- to the lamp-dish flower acetic that discipline the seventies are therefrom separated through scholar's research
It is 01-8) effective component for the treatment of apoplexy.
Due to the intrinsic face type molecular structure of lamp-dish flower acetic, lead to the compound water soluble and fat-soluble poor.?
In daily injection production process, using the carboxyl on glucuronic acid in alkaline aqueous solution and lamp-dish flower acetic molecule at salt,
Finally it is dissolved into aqueous solution.Small size prepares lamp-dish flower acetic aqueous solution process because of the poor solubility of lamp-dish flower acetic and dissolution speed
Spend that slow physicochemical property will not also constitute a threat to injection product quality and production process causes inconvenience.But it industrializes
During producing breviscapine B injection agent with liquid on a large scale, because lamp-dish flower acetic poor solubility and solution rate will lead to slowly
Entire liquid preparation time significantly extends, and lamp-dish flower acetic is therefore brought to generate catabolite in alkaline aqueous solution for a long time, finally
It is reflected in product quality that related substance is higher, and production process is longer.It is necessary to study a kind of new scutellarin crystal shapes
Formula can make enhanced dissolution rate of the lamp-dish flower acetic in alkaline aqueous solution.
Chinese patent CN200910164855.7 discloses scutellarin crystal I and preparation method thereof, provides crystallization
Quantity of solvent is few, and production cost is low, easy industrialized production, scutellarin crystal I of high income and preparation method thereof.Knot obtained
The lamp-dish flower acetic of crystalline form state has purity is high, use is safer, is mass produced or is configured to compared with existing Breviscapinun
Performance required for therapeutic preparation stablizes light, wet, hot etc., more stable in alkaline solution, be convenient for industrialized production,
Storage.CN201410269593.1 discloses lamp-dish flower acetic dihydrate crystal II and preparation method thereof, provides a kind of conjunction
At high-purity scutellarin dihydrate crystallization II, with without the crystallization water plant extract lamp-dish flower acetic and it has been reported that
Scutellarin crystal I compare with purity is high, stability it is good, it is low draw dissolubility moist, in water and ethyl alcohol it is good, will not
Have the advantages that deliquesce phenomenon.Above-mentioned lamp-dish flower acetic correlation crystal form patent does not refer to that lamp-dish flower acetic is molten in alkaline aqueous solution
Solve the problem of speed is promoted.
Oral administration solid drug is by body absorption and plays a role depending on the water-soluble of active pharmaceutical ingredient and penetrates internal organ
Viscous permeability of the membrane, wherein being dissolved as the rate-determining steps of absorption process.Its active constituent of about 90% drug in pharmacy industry
Included in solid particle, it is not soluble in water that there are about one thirds in these solid drugs compounds.Water-insoluble drug due to
It cannot be effectively dissolved in gastro-intestinal Fluid, therefore, limit its performance acted in human body.Improve the solubility and dissolution of drug
Rate has become a major challenge of pharmacy industry development.According to Noyes-Whitney equation, since grain diameter reduction causes
Specific surface area increase and high wettability, can promote particle it is quick dissolution (Chen Peng, Zhang little Gang micronization technology raising water
Insoluble drugs solubility [J] chemistry is notified to .2007,10:766-771).
The common method for reducing drug granule granularity mainly has low-temperature airflow comminuting method, ball-milling method, solid dispersion method etc..
First two method generally there are energy consumption is high, low efficiency, Granularity Distribution are wide, easily make thermally labile drug structure destroy with
The disadvantages of environment is polluted due to dust from flying in degradation, crushing process.Though and solid dispersion method improves medicine to a certain extent
The result of extraction of object, but operating process is more complex, and (Zhou Minyi, Chen Jianfeng, Liu Xiaolin recrystallization method prepare micro mist to higher cost
Change desk study [J] the chemical industry progress .2003 of brufen, 22 (5): 524-527).
Micropowder crystallization process is another important method for preparing micronized medicine, is the appearance of solid matter under certain condition
The technical method for promoting it to be micronized in product when crystallization, this method are not necessarily to special disintegrating apparatus, the grain size of micropowder overwhelming majority
At 50 microns hereinafter, and granularity uniformity it is good, amplitude variation it is smaller (micronization of Zhang Gengyuan ticagrelor and its crystal form,
And preparation method and medicinal application [P] Chinese patent: 201410033754.7,2014-01-24).
Up to the present, it does not disclose still both at home and abroad and the rapidly-soluble lamp-dish flower acetic knot of energy is obtained by micronization approach
Brilliant report.
Summary of the invention
The purpose of the present invention is overcoming the deficiencies of existing technologies, a kind of new, faster fleabane flower second of solution rate is provided
Plain crystal form.
It is a further object of the present invention to provide the preparation methods of this lamp-dish flower acetic crystal form.
Lamp-dish flower acetic crystal form of the present invention, is named as lamp-dish flower acetic crystal form III.
Lamp-dish flower acetic crystal form III of the present invention, is radiated, λ=1.5405A using Cu-K α, is indicated with 2 θ angles
X-ray powder diffraction spectral signature is as follows:
2θ | I/I0% |
8.02 | 73.14 |
9.51 | 13.27 |
10.18 | 36.85 |
14.34 | 37.46 |
16.18 | 100 |
19.13 | 10 |
21.18 | 13.86 |
25.89 | 24.74 |
26.83 | 27.63 |
29.06 | 15.95 |
38.73 | 15.01 |
46.56 | 11.09 |
Lamp-dish flower acetic crystal form III of the present invention, diffraction peak intensity is 100% at 2 position θ 16.18 of X-ray powder diffraction.
The dsc analysis endothermic transition temperature of lamp-dish flower acetic crystal form III of the present invention is 107-137 DEG C.
The fusion and decomposition temperature of lamp-dish flower acetic crystal form III of the present invention is 195-201 DEG C.
Lamp-dish flower acetic crystal form III provided by the present invention, is a kind of crystal form of lamp-dish flower acetic micronization, and partial size exists
50 microns hereinafter, preferable particle size at 30 microns hereinafter, preferable particle size is at 1-20 microns, it is 1-10 microns more preferable, and its powder
X-ray diffracting spectrum and existing scutellarin crystal powder X-ray diffracting spectrum it is significantly different.
The preparation method of lamp-dish flower acetic crystal form III of the present invention the following steps are included:
One, lamp-dish flower acetic is added in organic solvent, the additional amount of organic solvent is in room temperature to solvent reflux temperature
Under be completely dissolved lamp-dish flower acetic, then the solution of dissolution is slowly added in 5-12 times of liquor capacity of aqueous solvent, is gone forward side by side
Row stirring, makes lamp-dish flower acetic be precipitated and be dispersed in aqueous solvent immediately;
Two, it filters, isolates solid, be dried under reduced pressure the lamp-dish flower acetic crystal form III to get micronization.
Wherein, the speed of stirring is 500-1500r/min, and the organic solvent is methanol, ethyl alcohol, isopropanol, N, N-
One of dimethylformamide, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide are a variety of.
The aqueous solvent is the mixed solvent of water Yu above-mentioned organic solvent, such as methanol aqueous solution, ethanol water
Or isopropanol water solution etc..The dosage volume ratio of water and organic solvent is 100:0~40 in the aqueous solvent.
It should be noted that above-mentioned preparation method in, aqueous solvent can be water or the mixed solvent containing water, when water with
When the dosage volume ratio of organic solvent is 100:0, it is meant that aqueous solvent at this time is water.The water includes pure water, distillation
Water, deionized water or water for injection.
Described is dried under reduced pressure including the drying under the arbitrary temp of room temperature~60 DEG C.
Lamp-dish flower acetic crystal form III of the present invention has compared with not being micronized sample in methanol, ethyl alcohol, alkaline water
Solution rate in solution equal solvent faster the advantages of, especially in alkaline aqueous solution solution rate promotion become apparent.This
Outside, compared with not being micronized sample, impurity is less.It improves solution rate and reduces impurity, perhaps have little significance in some fields,
But in pharmaceutical field, improve solution rate even lesser numerical value can all bring it is more important as a result, reduce impurity even
It is the safety that lesser numerical value can all greatly improve drug.Lamp-dish flower acetic as injection bulk pharmaceutical chemicals, the two numerical value
It improves, time cost can be greatlyd save, improve product quality, bring extraordinary clinical effectiveness.
Solution rate test:
Precision weighs lamp-dish flower acetic highly finished product (not being micronized) and each 3 parts of lamp-dish flower acetic crystal form III (micronization), often
Part 10mg is separately added into alkaline aqueous solution (pH6-8), methanol, appropriate amount of ethanol under the conditions of 25 DEG C, and ultrasound makes it dissolve, record
Dissolution time.It the results are shown in Table 1, table 2, table 3.
Dissolution time (min) of the different lamp-dish flower acetic samples of table 1 in 100ml different solvents
It is shown from table 1, lamp-dish flower acetic crystal form III has faster compared with lamp-dish flower acetic highly finished product (not being micronized)
Solution rate.
The different lamp-dish flower acetic sample preparation 200L breviscapine B injection preparation dissolution times (h) of table 2
Sample ID | Alkaline aqueous solution (pH6-8) |
Lamp-dish flower acetic highly finished product (are not micronized) | 3.0 |
Scutellarin crystal III (embodiment 1) | 2.5 |
Scutellarin crystal III (embodiment 2) | 2.8 |
Scutellarin crystal III (embodiment 3) | 2.7 |
Scutellarin crystal III (embodiment 4) | 2.8 |
It is shown from table 2, when producing breviscapine B injection agent with liquid on a large scale, dissolution time is obviously increased, and is passed through micro-
The lamp-dish flower acetic crystal form III of dusting can significantly shorten liquid preparation time.
Table 3 is not micronized through micronization and preparation 200L lamp-dish flower acetic note with a collection of lamp-dish flower acetic sample
Penetrate the related substance testing result of preparation
Sample ID | Impurity (%) |
Lamp-dish flower acetic highly finished product (are not micronized) | 1.4 |
Scutellarin crystal III (embodiment 1) | 1.2 |
Show that compared with lamp-dish flower acetic highly finished product (not being micronized), impurity obviously subtracts lamp-dish flower acetic crystal form III from table 3
It is few.
Detailed description of the invention
Fig. 1 is the X-ray powder diffraction figure of scutellarin crystal III of the present invention.
Fig. 2 is that the DSC of scutellarin crystal III of the present invention schemes.
Fig. 3 is that the TG-DTA of scutellarin crystal III of the present invention schemes.
Fig. 4 is that the HPLC of scutellarin crystal III of the present invention schemes.
Specific embodiment
Embodiment 1:
It takes lamp-dish flower acetic highly finished product 1g to be added in 50ml methanol, is heated to reflux 20~25min and makes it completely dissolved, slowly
(or dropwise addition) is added into 300ml distilled water, side is added dropwise, and side stirring, mixing speed 800r/min, lamp-dish flower acetic is analysed immediately
Out and it is dispersed in water.Filtering, is stirred with distilled water and washes or rinse 2-4 times, is filtered, and is dried under reduced pressure to constant weight at 30 DEG C to get micro-
The scutellarin crystal III of dusting, yield 90%.Above-mentioned powder is taken to carry out powder diameter detection, powder average particle size 4-7
Micron.
Embodiment 2:
It takes lamp-dish flower acetic highly finished product 1g to be added in 45ml methanol, is heated to reflux 30min and makes it completely dissolved, be slowly added to
(or dropwise addition) into the mixed solution (V:V=360:40) of 400ml distilled water and ethyl alcohol, side is added dropwise, side stirring, and mixing speed is
750r/min, lamp-dish flower acetic are precipitated and are dispersed in water immediately.Filtering, is stirred with distilled water and washes or rinse 2-4 times, is filtered, 50
The scutellarin crystal III to constant weight to get micronization, yield 92% are dried under reduced pressure at DEG C.Above-mentioned powder is taken to carry out powder grain
Diameter detection, powder average particle size are 6-8 microns.
Embodiment 3:
It takes lamp-dish flower acetic highly finished product 1g to be added in the mixed solvent (V:V=8:2) of 60ml methanol and isopropanol, heats back
30~35min of stream makes it completely dissolved, and is slowly added to (or dropwise addition) into 800ml distilled water, and side is added dropwise, side stirring, stirring speed
Degree is 800r/min, and lamp-dish flower acetic is precipitated and is dispersed in water immediately.Filtering, is stirred with distilled water and washes or rinse 2-4 times, mistake
It filters, the scutellarin crystal III to constant weight to get micronization, yield 89% is dried under reduced pressure at 60 DEG C.Above-mentioned powder is taken to carry out
Powder diameter detection, powder average particle size are 6-9 microns.
Embodiment 4:
It takes lamp-dish flower acetic highly finished product 1g to be added in 60ml ethyl alcohol, is heated to reflux 30~35min and makes it completely dissolved, slowly
(or dropwise addition) is added into the mixed solution (V:V=550:50) of 600ml distilled water and isopropanol, side is added dropwise, side stirring, stirring
Speed is 900r/min, and lamp-dish flower acetic is precipitated immediately and is dispersed in the mixed solution.Filtering, is stirred with distilled water and washes or rinse
It 2-4 times, filters, the scutellarin crystal III to constant weight to get micronization, yield 87% is dried under reduced pressure at 45 DEG C.It takes above-mentioned
Powder carries out powder diameter detection, and powder average particle size is 3-7 microns.
The purity testing of lamp-dish flower acetic in scutellarin crystal III:
Chromatographic condition and system suitability: using octadecylsilane chemically bonded silica as filler;With methanol -0.1%
Phosphoric acid solution (40:60) is mobile phase;Flow velocity is 1.0ml per minute;40 DEG C of column temperature;Detection wavelength 335nm.Number of theoretical plate is by open country
Scutelloside, which calculates, should be not less than 5000.
The preparation of reference substance solution takes scutellarin reference substance 10mg, accurately weighed, sets in 100ml measuring bottle, adds methanol
70ml, ultrasonic treatment (power 300W, frequency 50kHz) 45 minutes are taken out, and room temperature is placed, and methanol dilution is added to shake up to scale,
To obtain the final product.
The preparation of test solution takes this product 10mg, accurately weighed, sets in 100ml measuring bottle, adds methanol 70ml, ultrasonic treatment
(power 300W, frequency 50kHz) 45 minutes takes out, places room temperature, and methanol dilution is added to shake up to scale, filters, takes subsequent filtrate,
To obtain the final product.
Measuring method is accurate respectively to draw reference substance solution and each 5 μ l of test solution, injects liquid chromatograph, measures, i.e.,
?.
Impurity determination: taking this product appropriate (being equivalent to scutellarin 20mg), set in 50ml measuring bottle, add methanol appropriate, ultrasound
It handles (power 300W, frequency 50kHz) 45 minutes, puts to room temperature, add methanol dilution to scale, shake up, as test solution.
Precision measures test solution 1ml, sets in 100ml measuring bottle, adds methanol dilution to scale, shake up, as reference substance solution.According to
Chromatographic condition under [assay] item takes 5 μ l of contrast solution, injects liquid chromatograph, adjusts detection sensitivity, makes principal component
The peak height of chromatographic peak is the 10% of full scale, then accurate measurement test solution and each 5 μ l of contrast solution, is injected separately into liquid phase color
Spectrometer, 2.5 times of record chromatogram to principal component peak retention time.In test solution chromatography, the sum of other compositions peak area
It is not greater than 2 times of contrast solution main peak peak area.
Claims (5)
1. a kind of lamp-dish flower acetic crystal form, it is characterised in that be named as lamp-dish flower acetic crystal form III, partial size is 1-10 microns, is used
Cu-K α radiation, λ=1.5405A are as follows with the X-ray powder diffraction spectral signature that 2 θ angles indicate:
。
2. lamp-dish flower acetic crystal form as described in claim 1, it is characterised in that X-ray powder diffraction is spread out at 2 position θ 16.18
Penetrating peak intensity is 100%.
3. lamp-dish flower acetic crystal form as described in claim 1, it is characterised in that its dsc analysis endothermic transition temperature is 107-
137℃。
4. lamp-dish flower acetic crystal form as described in claim 1, it is characterised in that its fusion and decomposition temperature is 195-201 DEG C.
5. the preparation method of lamp-dish flower acetic crystal form as described in claim 1, it is characterised in that the following steps are included:
One, lamp-dish flower acetic is added in organic solvent, the additional amount of organic solvent is to make under room temperature to solvent reflux temperature
Lamp-dish flower acetic is completely dissolved, then the solution of dissolution is slowly added in 5-12 times of liquor capacity of aqueous solvent, and is stirred
It mixes, lamp-dish flower acetic is made to be precipitated and be dispersed in aqueous solvent immediately;
Two, it filters, isolates solid, be dried under reduced pressure the lamp-dish flower acetic crystal form III to get micronization;
The mixing speed be 500-1500r/min, the organic solvent be one of methanol, ethyl alcohol, isopropanol or
A variety of, the aqueous solvent is the mixed solvent of water Yu above-mentioned organic solvent, water and organic solvent in the aqueous solvent
Dosage volume ratio be 100:0~40.
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101993462A (en) * | 2009-08-11 | 2011-03-30 | 昆明制药集团股份有限公司 | Scutellarin crystal I and preparation method thereof |
CN103102337A (en) * | 2013-01-24 | 2013-05-15 | 昆明理工大学 | Preparation method of wild baicalein |
CN105273018A (en) * | 2014-06-17 | 2016-01-27 | 昆明制药集团股份有限公司 | Scutellarin dihydrate crystal II and preparation method thereof |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101993462A (en) * | 2009-08-11 | 2011-03-30 | 昆明制药集团股份有限公司 | Scutellarin crystal I and preparation method thereof |
CN103102337A (en) * | 2013-01-24 | 2013-05-15 | 昆明理工大学 | Preparation method of wild baicalein |
CN105273018A (en) * | 2014-06-17 | 2016-01-27 | 昆明制药集团股份有限公司 | Scutellarin dihydrate crystal II and preparation method thereof |
Non-Patent Citations (1)
Title |
---|
高纯度灯盏乙素的多晶型制备及改善其溶解性的初步研究;冯博闻;《中国优秀硕士学位论文全文数据库-医药卫生科技辑》;20160815(第8期);第33-52页 |
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