CN107141328A - A kind of Vidarabine Monophosphate novel crystal forms and preparation method thereof - Google Patents
A kind of Vidarabine Monophosphate novel crystal forms and preparation method thereof Download PDFInfo
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- CN107141328A CN107141328A CN201710447191.XA CN201710447191A CN107141328A CN 107141328 A CN107141328 A CN 107141328A CN 201710447191 A CN201710447191 A CN 201710447191A CN 107141328 A CN107141328 A CN 107141328A
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
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- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07B2200/13—Crystalline forms, e.g. polymorphs
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Abstract
The invention belongs to pharmaceutical technology field.Disclose a kind of novel crystal forms of Vidarabine Monophosphate and preparation method thereof.New crystal formation is characterized with means such as XRD, infrared spectrums, finds that the novel crystal forms have more excellent physical and chemical performance by study on the stability contrast.Vidarabine Monophosphate novel crystal forms preparation method of the present invention is simple, is easily controlled, favorable reproducibility, target crystal formation crystallinity height is obtained, with preferable Development volue.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of novel crystal forms of Vidarabine Monophosphate and preparation method thereof.
Background technology
Vidarabine Monophosphate is antiviral oligonucleotide, is arabinosy ladenosine（Ara-A）Second generation preparation.Can selectivity
Suppress varial polymerases and nucleotide reducing enzymatic activity, there is extensive inhibitory action to DNA virus.Current China is mainly used in
Stomatitis, dermatitis, encephalitis and cytomegalovirus infection caused by chronic viral hepatitis and herpesvirus infection.It can suppress B-mode
The duplication of hepatitis viruse, so as to reach the effect that HBV DNA and HBrAg the moon turn, it is compared to the sensitiveness that viral DNA-P suppresses
Host cell DNA-P sensitiveness is high 40 times.Due to its outstanding curative effect and security, Vidarabine Monophosphate has turned at present
After the most salable treatment hepatitis B medication, treatment herpesvirus infection more more popular than GCV and property after interferon
Sick medication.
Crystal formation is to influence one of key factor of drug quality, curative effect and preparation processing performance.Polymorphism refers to solid
Body material is with two or more different spaces arrangement mode, the solid state with different physicochemical properties of formation
Phenomenon.Different crystal forms have different colors, fusing point, dissolving, dissolving out capability, chemical stability, reactivity, mechanical stability
The preparation processing performance of medicine is directly affected Deng, these characteristics, and stability, solubility and the biology profit of medicine can be influenceed
Expenditure, and then have influence on quality, security, validity and its application of medicine.There is polymorphic in Vidarabine Monophosphate, in
State's patent（CN201310093504.8）Report prepares a kind of Vidarabine Monophosphate using methyl ethyl ketone as solvent
Crystalline compounds, its infrared spectrum is different from the former standard diagram for grinding bulk drug, with more preferable dissolubility, makes monophosphate arabinose
Solubility in adenosine water（20℃）115.6mg/mL is promoted to by 98.5mg/mL.Patent CN201310048253.1 is provided
A kind of process for purification of new Vidarabine Monophosphate, it is intended to solve prior art by water as the higher generation of solvent temperature
The problem of accessory substance, the Vidarabine Monophosphate crystal that the patent is obtained does not provide solubility data.2016 entitled《It is a kind of
Vidarabine Monophosphate crystal-form compound》Chinese patent CN105541945 A（Application number 201610125180.5）Carry out
Numerous studies, have been made Vidarabine Monophosphate crystal compound, it is in water by changing crystal formation solvent, crystallization condition
Solubility is better than other Vidarabine Monophosphates.But its preparation process condition is harsh, and N, N- dimethyl formyls have been used in preparation
Amine and methanol and acetonitrile, toxicity are larger, and cost is higher, do not meet the requirement of Green Chemistry.In fact, in DMF backflow temperature
The lower solution blackening quickly of degree, Vidarabine Monophosphate degraded is serious, and it is higher to obtain product impurity content through method crystallization.
Therefore, study and prepare the more preferable Vidarabine Monophosphate crystal-form compound of stability and have great importance.
The content of the invention
The Vidarabine Monophosphate novel crystal forms of the present invention, are examined using Brooker D8 AdvanceX x ray diffractometer xs in room temperature
Survey, 2 θ angle sweeps are from 5 degree to 60 degree, Cu K, sweep speed：0.1 °/step, obtained powder x-ray diffraction TuPu method absorbs
Peak（2θ）As follows with D values, error is ± 0.2.As a result novel crystal forms are shown in 2 θ angles 5.49,11.16,13.75,16.87,
18.83,20.51,25.83,26.88,27.39,28.40 there is characteristic peak at ± 0.2 °.
2- of the relative intensity more than 50% in the compound of above-mentioned crystal form, wherein crystal X- powder diffraction spectrums
Theta angles, the relative intensity is represented with strongest line percentage in collection of illustrative plates：
| 2-Theta angles | Relative intensity（%） |
| 11.16 | 66.2 |
| 16.87 | 100 |
2-Theta angle of the relative intensity more than 20% in the compound of above-mentioned crystal form, wherein crystal X- powder diffraction spectrums,
The relative intensity is represented with strongest line percentage in collection of illustrative plates：
| 2-Theta angles | Relative intensity（%） |
| 11.16 | 66.2 |
| 13.75 | 26.5 |
| 16.87 | 100 |
| 18.83 | 28.9 |
| 20.51 | 28.8 |
| 27.39 | 22.2 |
2-Theta angle of the relative intensity more than 10% in the compound of above-mentioned crystal form, wherein crystal X- powder diffraction spectrums,
The relative intensity is represented with strongest line percentage in collection of illustrative plates：
| 2-Theta angles | Relative intensity（%） |
| 5.49 | 17.3 |
| 11.16 | 66.2 |
| 13.75 | 26.5 |
| 16.87 | 100 |
| 18.83 | 28.9 |
| 20.51 | 28.8 |
| 25.83 | 14.7 |
| 26.88 | 11.3 |
| 27.39 | 22.2 |
| 28.40 | 12.5 |
It should be noted that in powder sample X ray diffracting spectrum, the diffraction spectrogram obtained by crystalline compounds is specifically brilliant
Type is often characteristic, wherein bands of a spectrum（Especially in low angle）Relative intensity may be because of crystallization condition, particle diameter, mixed
The difference of the relative amount of compound and other test conditions and the advantage orientation effect that produces and change.Therefore, the phase of diffraction maximum
It is not characteristic to targeted crystal to intensity, when judging whether identical with known crystal formation, it should be noted that
The position at peak rather than their relative intensity.In addition, judge crystal formation whether when should be noted that holding organic conception because simultaneously
It is not that a diffracted ray represents a thing phase, but a set of specific " d-I/I1" data just represent a certain thing phase.It is also pointed out that
, in the identification of mixture, because the factors such as content decline can cause the missing of part diffracted ray, now, without relying on
The whole bands of a spectrum observed in high-purity sample, or even a bands of a spectrum may also be characteristic to given crystal.
The Vidarabine Monophosphate novel crystal forms of the present invention, using the Nicolet-Magna FT-IR of U.S. Buddhist nun high-tensile strength company
750 infrared spectrometers detect in room temperature, pressing potassium bromide troche, and detection range is：4000-500 centimetres-1Wave number, its infrared spectrum
3353 ± 2,3139 ± 2,3058 ± 2,1702 ± 2,1676 ± 2,1555 ± 2,1492 ± 2,1413 ± 2,
1212±2, 1141±2, 1077±2, 1043±2, 957±2, 873±2, 795±2, 591±2cm-1There is feature at place
Peak.
The preparation of Vidarabine Monophosphate novel crystal forms of the present invention uses Vidarabine Monophosphate crude product or known crystal formation
Vidarabine Monophosphate is raw material, using absolute ethyl alcohol or Mixed Ethanol-Water Solvent as recrystallisation solvent, by turning brilliant or reaction
Method for crystallising is prepared, and specific method is as follows：
Vidarabine Monophosphate crude product or known crystal formation Vidarabine Monophosphate sample are hanged and are dissolved in water or ethanol water mixed solvent
In, add appropriate alkali regulation solution ph to 6 or so samples and be completely dissolved, the ethanol of certain volume is being added into solution,
Suitable temperature is heated to, the water or ethanol solution of hydrochloric acid or phosphoric acid, regulation solution ph to 3-3.5 or so is slowly added dropwise, it is natural
Cooling and stirring crystallization, is filtered, and is dried, is produced Vidarabine Monophosphate novel crystal forms.
Or, be suspended in Vidarabine Monophosphate crude product, highly finished product or known crystal formation Vidarabine Monophosphate sample anhydrous
Ethanol or a certain proportion of ethanol water in the mixed solvent, are heated to suitable temperature 1 ~ 24h of outstanding stirring, are cooled to room temperature, filter, do
It is dry, produce Vidarabine Monophosphate novel crystal forms.
Wherein described ethanol is that mass percentage content is absolute ethyl alcohol, pure 95% analysis, chemical straight alcohol or industry
Alcohol, preferably industrial alcohol.The temperature conditionss are 40 DEG C to solvent reflux temperature, preferably 60 ~ 70 DEG C；The drying condition is
Vacuum drying or forced air drying, dry temperature is room temperature to 110 DEG C, preferably 50 ~ 80 DEG C；
Using the relevant material of Vidarabine Monophosphate and detection method of content described in Chinese Pharmacopoeia, it is bonded with octadecylsilane
Silica gel is filler；With 0.05mol/L potassium dihydrogen phosphate（Plus 10% tetrabutylammonium regulation pH to 6.5）- methanol
（90：10）For mobile phase；Flow velocity is 1.0ml/min, and Detection wavelength is 259nm.Vidarabine Monophosphate peak and other impurities peak
Separating degree should meet regulation, theoretical cam curve based on Vidarabine Monophosphate peak, should must not be less than 1500.Determination method is：Essence
The close Vidarabine Monophosphate sample that weighs is appropriate, plus the solution in every 1ml containing about 160 μ g is made in flowing phased soln and diluting, and makees
For need testing solution；Precision measures test liquid 1mL again, puts in 100mL volumetric flasks, plus mobile phase is diluted to scale, shakes up, and makees
For 1% own control solution.The μ L of contrast solution 20 are measured, injection liquid chromatograph analysis records chromatogram.It is full to adjust peak height
The 20 ~ 25% of range, then precision measure the μ L injecting chromatographs of need testing solution 20, record chromatogram to need testing solution principal component
2.5 times of peak retention time, need testing solution should cannot be greater than reference substance solution main peak such as aobvious impurity peaks, impurity peak area summation
5 times of area（0.5%）.Novel crystal forms obtained by this experiment and original are ground into crystal formation product and under equal conditions carry out stability pair
Than research, experimental method is as follows：1）It is former that high temperature experiment takes the Vidarabine Monophosphate crystal-form compound and original of the present invention to grind crystal formation
Expect medicine sample, test sample 0.2g is claimed respectively, put in measuring cup and number, opening is put in 60 DEG C of constant temperature in baking oven, place 10 days, respectively
In the 5th day, each sampling 0.2g liquid phases detection in the 10th day, analysis result was as shown in the table：
2）High humidity experiment takes the Vidarabine Monophosphate crystal-form compound and original of the present invention to grind crystal form samples and be laid in culture dish
（About 2mm thickness）, it is placed under conditions of 25 DEG C of room temperature, 2 DEG C of scholar, relative humidity RH90% scholar 5% and places 10 days, in the 5,10 days
Sampling detection.Analysis result is as shown in the table：
From above-mentioned experimental data, Vidarabine Monophosphate crystal compound of the invention grinds crystal form samples than original to be had more
Good stability.
It is a further object of the present invention to provide a kind of pharmaceutical composition comprising above-mentioned Vidarabine Monophosphate novel crystal forms and
Its application in treating hepatitis B.It is used in the present invention in oral, subcutaneous, intramuscular or intravenous pharmaceutical composition, institute
State reactive compound individually or with another reactive compound administering drug combinations.The appropriate example of form of medication includes the shape orally provided
Formula such as tablet, capsule, pill, particle and solution or oral suspension, through subcutaneous, intramuscular, intravenous administration form for example
Parenteral solution, transfusion or powder pin etc..
The Vidarabine Monophosphate crystal compound of the present invention has more preferable chemical stability, and dissolubility is more excellent, carries
High Drug safety, beneficial to the long term storage of medicine.
Brief description of the drawings
Fig. 1 is the X-ray powder diffraction of Vidarabine Monophosphate novel crystal forms（XRPD）Spectrogram.
Fig. 2 is infrared spectrum (IR) figure of Vidarabine Monophosphate novel crystal forms.
Embodiment
Technical scheme is described in further detail below in conjunction with specific embodiment, but the embodiment does not limit this
The protection domain of invention.
Embodiment 1
10g Vidarabine Monophosphates crude product is hanged and is dissolved in 100 mL deionized waters, hydrogenation aqueous solution of sodium oxide regulation pH to 6 is left
Right sample is completely dissolved, then adds 100 mL absolute ethyl alcohols into the solution, is warming up to 60 DEG C, aqueous hydrochloric acid solution is slowly added dropwise,
PH value of solution is adjusted to 3-3.5, natural cooling stirring and crystallizing, filtering, in 50 DEG C of normal pressures or decompression drying, obtains Vidarabine Monophosphate
Novel crystal forms.
Embodiment 2
10g Vidarabine Monophosphate originals are ground crystal form samples and hanged and are dissolved in 100 mL deionized waters, hydrogenation aqueous solution of sodium oxide is adjusted
Section pH is completely dissolved to 6 or so samples, then adds 100 mL absolute ethyl alcohols into the solution, is warming up to 60 DEG C, salt is slowly added dropwise
Aqueous acid, regulation pH value of solution to 3-3.5, natural cooling stirring and crystallizing, filtering, in 50 DEG C of normal pressures or decompression drying, obtains single phosphorus
Sour arabinosy ladenosine novel crystal forms.
Embodiment 3
10g Vidarabine Monophosphates crude product is hanged and is dissolved in 100 mL deionized waters, plus aqueous sodium carbonate regulation pH to 6 or so
Sample is completely dissolved, then adds 100 mL absolute ethyl alcohols into the solution, is warming up to 60 DEG C, ethanol solution hydrochloride is slowly added dropwise,
PH value of solution is adjusted to 3-3.5, natural cooling stirring and crystallizing, filtering, in 60 DEG C of normal pressures or decompression drying, obtains Vidarabine Monophosphate
Novel crystal forms.
Embodiment 4
10g Vidarabine Monophosphates crude product is hanged and is dissolved in 100 mL deionized waters, plus sodium acid carbonate adjusts pH to 6 or so samples
It is completely dissolved, then 100 mL absolute ethyl alcohols is added into the solution, be warming up to 60 DEG C, phosphate aqueous solution is slowly added dropwise, adjusts pH
To 3-3.5, natural cooling stirring and crystallizing, filtering, in 70 DEG C of normal pressures or decompression drying, obtains Vidarabine Monophosphate novel crystal forms.
Embodiment 5
10g Vidarabine Monophosphates crude product is hanged and is dissolved in 100 mL deionized waters, ammonification water regulation pH is complete to 6 or so samples
Dissolving, then 100 mL absolute ethyl alcohols are added into the solution, 60 DEG C are warming up to, phosphate aqueous solution is slowly added dropwise, pH to 3- is adjusted
3.5, natural cooling stirring and crystallizing, filtering, in 70 DEG C of normal pressures or decompression drying, obtains Vidarabine Monophosphate novel crystal forms.
Embodiment 6
By the outstanding 200 mL volume ratios that are dissolved in of 10g Vidarabine Monophosphates crude product in 50% ethanol water, ammonification water adjusts pH to 6
Left and right sample is completely dissolved, and is warming up to 60 DEG C, and aqueous hydrochloric acid solution is slowly added dropwise, and adjusts pH to 3-3.5, natural cooling stirring analysis
Crystalline substance, filtering, in 80 DEG C of normal pressures or decompression drying, obtains Vidarabine Monophosphate novel crystal forms.
Embodiment 7
10g Vidarabine Monophosphates crude product is hanged and is dissolved in the ethanol water that 200 mL volume ratios are 60%, plus sodium acid carbonate regulation pH
It is completely dissolved to 6 or so samples, is warming up to 60 DEG C, ethanol solution hydrochloride is slowly added dropwise, adjust pH to 3-3.5, natural cooling is stirred
Crystallization is mixed, filters, in 90 DEG C of normal pressures or decompression drying, obtains Vidarabine Monophosphate novel crystal forms.
Embodiment 8
10g Vidarabine Monophosphates crude product is hanged and is dissolved in the ethanol water that 200 mL volume ratios are 60%, 60 DEG C, ammonification are warming up to
Water adjusts pH and is completely dissolved to 6 or so samples, then aqueous hydrochloric acid solution is slowly added dropwise, and adjusts pH to 3-3.5, natural cooling stirring analysis
Crystalline substance, filtering, in 100 DEG C of normal pressures or decompression drying, obtains Vidarabine Monophosphate novel crystal forms.
Embodiment 9
10g Vidarabine Monophosphates crude product is hanged and is dissolved in the ethanol water that 200 mL volume ratios are 70%, 70 DEG C, ammonification are warming up to
Water adjusts pH and is completely dissolved to 6 or so samples, then aqueous hydrochloric acid solution is slowly added dropwise, and adjusts pH to 3-3.5, natural cooling stirring analysis
Crystalline substance, filtering, in 50 DEG C of normal pressures or decompression drying, obtains Vidarabine Monophosphate novel crystal forms.
Embodiment 10
Known crystal formation Vidarabine Monophosphate sample is suspended in absolute ethyl alcohol, 50 DEG C of outstanding stirring 3h is heated to, filters while hot,
Dry, produce Vidarabine Monophosphate novel crystal forms.
Embodiment 11
Known crystal formation Vidarabine Monophosphate sample is suspended in absolute ethyl alcohol, 60 DEG C of outstanding stirring 1h is heated to, is cooled to room
Temperature, is filtered, and is dried, is produced Vidarabine Monophosphate novel crystal forms.
Embodiment 12
Known crystal formation Vidarabine Monophosphate sample is suspended in absolute ethyl alcohol, 70 DEG C of outstanding stirring 1h is heated to, is cooled to room
Temperature, is filtered, and is dried, is produced Vidarabine Monophosphate novel crystal forms.
Embodiment 13
Known crystal formation Vidarabine Monophosphate sample is suspended in absolute ethyl alcohol, solvent refluxing is heated to, stirring 1h, cooling is hanged
To room temperature, filter, dry, produce Vidarabine Monophosphate novel crystal forms.
Embodiment 14
Known crystal formation Vidarabine Monophosphate sample is suspended in the ethanol water that volume ratio is 50%, heats 50 DEG C, hang stirring 1-
3h, is filtered while hot, is dried, is produced Vidarabine Monophosphate novel crystal forms.
Embodiment 15
Known crystal formation Vidarabine Monophosphate sample is suspended in the ethanol water that volume ratio is 60%, heats 60 DEG C, hang stirring 1-
3h, is filtered while hot, is dried, is produced Vidarabine Monophosphate novel crystal forms.
Embodiment 16
Known crystal formation Vidarabine Monophosphate sample is suspended in the ethanol water that volume ratio is 70%, heats 60 DEG C, hang stirring 1-
3h, is cooled to room temperature, filters, and dries, produces Vidarabine Monophosphate novel crystal forms.
Embodiment 17
Known crystal formation Vidarabine Monophosphate sample is suspended in the ethanol water that volume ratio is 80%, heats 70 DEG C, hang stirring 1-
3h, is cooled to room temperature, filters, and dries, produces Vidarabine Monophosphate novel crystal forms.
Embodiment 18
Known crystal formation Vidarabine Monophosphate sample is suspended in 95% ethanol, outstanding stirring 1-3h is heated to reflux, is cooled to room
Temperature, is filtered, and is dried, is produced Vidarabine Monophosphate novel crystal forms.
Finally it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention and it is unrestricted, although ginseng
The present invention is described in detail according to preferred embodiment, it will be understood by those within the art that, can be to invention
Technical scheme is modified or equivalent substitution, and without departing from the spirit and scope of technical solution of the present invention, it all should cover
In scope of the presently claimed invention.
Claims (9)
1. a kind of novel crystal forms of Vidarabine Monophosphate, it is characterised in that with 2θThe X-ray powder diffraction that angle is represented is about：
5.49,1.16,13.75,16.87,18.83,20.51,25.83,26.88,27.39,28.4 0 ± 0.2 ° etc.
With characteristic peak.
2. a kind of novel crystal forms of Vidarabine Monophosphate, it is characterised in that its infrared spectrum is 3353 ± 2,3139 ± 2,3058
±2, 1702±2, 1676±2, 1555±2, 1492±2, 1413±2, 1212±2, 1141±2, 1077±2,
1043±2, 957±2, 873±2, 795±2, 591±2 cm-1There is characteristic peak at wave number.
3. a kind of preparation method of Vidarabine Monophosphate novel crystal forms, it is characterised in that using Vidarabine Monophosphate crude product or
Known crystal formation Vidarabine Monophosphate is raw material, using ethanol or Mixed Ethanol-Water Solvent as recrystallisation solvent, by turn it is brilliant or
Reactive crystallization is made.
4. according to claim 1 and 2, it is characterised in that described Vidarabine Monophosphate crude product or known crystal formation monophosphate arabinose
The purity of adenosine is in 40% ~ 100%, preferably more than 90%, more preferably more than 95%.
5. according to claim 2, it is characterised in that described ethanol is absolute ethyl alcohol, and the ratio of second alcohol and water is 50-100:0,
It is preferred that absolute ethyl alcohol and 95% ethanol.
6. described in cleaning solvent be 95-100% ethanol.
7. according to claim 2, it is characterised in that the temperature conditionss are room temperature to alcohol reflux temperature, preferably 60 ~ 70 DEG C；Institute
It is vacuum drying or forced air drying to state drying condition, and dry temperature is room temperature to 110 DEG C, preferably 70 ~ 100 DEG C；
A kind of pharmaceutical composition, the Vidarabine Monophosphate crystal-form compound of the claim 1-2 comprising therapeutically effective amount and
Pharmaceutically acceptable carrier.
8. the pharmaceutical composition of claim 7, it is used for oral, subcutaneous, intramuscular or intravenous administration, particularly preferably freezes thousand
Powder-injection.
9. application of the claim 7-8 pharmaceutical composition in treatment hepatitis B.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114736258A (en) * | 2022-04-18 | 2022-07-12 | 北京斯利安药业有限公司 | Crystal form of cytarabine hydrochloride and preparation method and application thereof |
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| CN1560065A (en) * | 2004-03-05 | 2005-01-05 | 陈铁钎 | Synthesis process of adenosine aose monophosphate |
| CN103122017A (en) * | 2013-02-06 | 2013-05-29 | 广东先强药业股份有限公司 | Refining method of vidarabine monophosphate |
| CN103159815A (en) * | 2013-03-22 | 2013-06-19 | 海南中化联合制药工业股份有限公司 | Monophosphate vidarabine crystalline compound, medical composition and preparation method thereof |
| CN105039466A (en) * | 2015-06-10 | 2015-11-11 | 海南中化联合制药工业股份有限公司 | Preparation method of vidarabine monophosphate |
| CN105541945A (en) * | 2016-03-07 | 2016-05-04 | 邓爱相 | Crystal form compound of Ara-ATP |
| CN106866763A (en) * | 2017-04-17 | 2017-06-20 | 上海应用技术大学 | A kind of synthesis technique of Vidarabine Monophosphate |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4123609A (en) * | 1976-11-03 | 1978-10-31 | Warner-Lambert Company | Process for the production of 9-(β-D-arabinofuranosyl)adenine, 5'-phosphate |
| CN1560065A (en) * | 2004-03-05 | 2005-01-05 | 陈铁钎 | Synthesis process of adenosine aose monophosphate |
| CN103122017A (en) * | 2013-02-06 | 2013-05-29 | 广东先强药业股份有限公司 | Refining method of vidarabine monophosphate |
| CN103159815A (en) * | 2013-03-22 | 2013-06-19 | 海南中化联合制药工业股份有限公司 | Monophosphate vidarabine crystalline compound, medical composition and preparation method thereof |
| CN105039466A (en) * | 2015-06-10 | 2015-11-11 | 海南中化联合制药工业股份有限公司 | Preparation method of vidarabine monophosphate |
| CN105541945A (en) * | 2016-03-07 | 2016-05-04 | 邓爱相 | Crystal form compound of Ara-ATP |
| CN106866763A (en) * | 2017-04-17 | 2017-06-20 | 上海应用技术大学 | A kind of synthesis technique of Vidarabine Monophosphate |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114736258A (en) * | 2022-04-18 | 2022-07-12 | 北京斯利安药业有限公司 | Crystal form of cytarabine hydrochloride and preparation method and application thereof |
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Application publication date: 20170908 |