CN109134566A - A kind of 1/20 water Ribavirin compound - Google Patents
A kind of 1/20 water Ribavirin compound Download PDFInfo
- Publication number
- CN109134566A CN109134566A CN201710709626.3A CN201710709626A CN109134566A CN 109134566 A CN109134566 A CN 109134566A CN 201710709626 A CN201710709626 A CN 201710709626A CN 109134566 A CN109134566 A CN 109134566A
- Authority
- CN
- China
- Prior art keywords
- water
- ribavirin
- compound
- ribavirin compound
- comparative example
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07H19/056—Triazole or tetrazole radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of 1/20 water Ribavirin compound, every mole of Ribavirin compound contains 1/20 mole of water.The present invention by by Ribavirin crude product it is soluble in water after, control solution temperature and pH value, 1/20 water Ribavirin compound is made in the crystallization in aqueous acetonitrile agent.Product purity produced by the present invention is high, and stability is good, has and value is applied even more extensively.
Description
Technical field
The invention belongs to chemical engineering medicine crystallization technique fields, are related to 1/20 water Ribavirin compound of one kind and its system
Method.
Background technique
Ribavirin is a kind of non-selective ucleosides broad-spectrum antiviral drug, belongs to monophosphate inosine (IMP)
Dehydrogenase inhibitor participates in guanine metabolism in human body, interferes the biosynthesis of guanine, the duplication of virus prevented, to more
Kind DNA and RNA virus have inhibiting effect.Viral pneumonia caused by clinical treatment Respiratory Syncytial Virus(RSV) and bronchus
Inflammation, influenza, encephalitis, varicella, rubeola, bleb etc..
There are three types of methods for the synthesis of Ribavirin: chemical method, fermentation method, enzymatic method
Chemical method is such as: CN 101891786A is condensed by 1,2,3,5-Tetra-O-Acetyl-D-Ribose and triazole methyl esters, then benefit bar is made in ammonolysis
Wei Lin.
Fermentation method is such as: CN 105483189A is to be overexpressed the genetic engineering bacterium BL21/Pet- of purine nucleoside phosphorylase
His-pupG is production bacterial strain, using lactose Fiber differentiation cell, in phosphate buffer, catalysis substrate guanosine and 1,2,4-
Triazole -3- formamide prepares Ribavirin.
For enzymatic method with inosine, guanosine, xanthosine or D-ribose -1- phosphate and 1,2,4- triazole -3- carboxylic acid amides are raw material,
Ribavirin is synthesized under the action of nucleoside phosphorylase esterase.
The Ribavirin of above-mentioned three kinds of methods preparation, haves the shortcomings that purity difference and stability are poor, the present inventor is
A kind of purity is high, stability is made by carrying out numerous studies to the factor for influencing its crystallization in the stabilization for improving Ribavirin
Good Ribavirin compound.
Summary of the invention
The invention discloses the new solvates of one kind of Ribavirin, are more specifically 1/20 water Ribavirin chemical combination
Object, i.e. every mole of Ribavirin compound contain 1/20 mole of water, molecular formula C8H12N4O51/20H2O, and molecular weight is
245.11 structural formula is as follows:
1/20 water Ribavirin compound of the present invention, preparation the following steps are included:
It adds water in container, controls temperature, Ribavirin crude product, stirring and dissolving, with disodium hydrogen phosphate and phosphorus is added
Acid dihydride sodium controls pH value, adds active carbon, stirring and adsorbing decoloration, and decompression filters, and is rinsed with water filter cake, takes filtrate to be added anti-
It answers in kettle, reduces temperature, be slowly added to acetonitrile, stand crystallization, decompression filters, and filter cake is washed with acetonitrile, is dried under reduced pressure, and obtains 1/20
Water Ribavirin compound.
Preferably, described controlled at 40~70 DEG C in above-mentioned preparation method, it is highly preferred that controlled at 50~
60℃。
Preferably, in above-mentioned preparation method, the control pH value is 4~7, it is highly preferred that control pH value is 5~6.
Preferably, in above-mentioned preparation method, the crystallization temperature is 0~30 DEG C, it is highly preferred that crystallization temperature is 10~20
℃。
Preferably, in above-mentioned preparation method, the crystallization time is 1~5h, it is highly preferred that the crystallization time is 2~4h.
Preferably, in above-mentioned preparation method, the drying temperature be 30~70 DEG C, it is highly preferred that drying temperature be 40~
60℃。
Preferably, in above-mentioned preparation method, the drying time is 0.5~3h, it is highly preferred that drying temperature is 1~2h.
Karl_Fischer method is that one of the most single-minded, accurate method, the present invention are public in moisture method in various measurement substances
Between 0.32~0.43%, theoretical water content is the Ribavirin compound Karl_Fischer method measurement moisture content opened
0.37%, it may be determined that each Ribavirin compound of the present invention contains 1/20 mole of water.
1/20 water Ribavirin compound of the present invention, TG are analyzed the results show that weightlessness about 0.34%, Li Bawei
The theoretical percentage composition of water is 0.37% in standing forest, referring to expense Xiu Shi method measure Ribavirin moisture content be 0.32~
0.43%, and it is 0.34% that experiment, which measures TG weightlessness, is consistent substantially with theoretical water content.It can be inferred that Ribavirin TG is weightless
It is caused by removing water, and every mole of Ribavirin contains 1/20 mole of water.As shown in Fig. 1.Data are by heat analysis-mass spectrometer
(NETZSCH STA 449C) analysis obtains.Analysis condition are as follows: 2~10mg of sample, alumina crucible, high pure nitrogen do reaction gas
With protection gas, flow is respectively 40ml/min and 30ml/min, and heating rate 10K/min, temperature test range is 25~400
℃.Sample decomposition temperature is about 254.9 DEG C.
1/20 water Ribavirin compound of the present invention, infrared spectroscopy are 3451.7 ± 2cm in wave number-1,
3349.1±2cm-1, 2955.6 ± 2cm-1, 1663.3 ± 2cm-1, 1502.8 ± 2cm-1, 1438.4 ± 2cm-1, 1362.1 ±
2cm-1, 1234.6 ± 2cm-1, 1070.6 ± 2cm-1, 958.7 ± 2cm-1, 836.6 ± 2cm-1, 773.2 ± 2cm-1There is feature at place
Absorption peak, as shown in Fig. 2.Examination of infrared spectrum condition are as follows: Agilent Cary 630, pressing potassium bromide troche.
1/20 water Ribavirin compound of the present invention, x-ray diffractogram of powder spectrum are 11.97 in 2 θ of the angle of diffraction
± 0.2 °, 13.45 ± 0.2 °, 18.22 ± 0.2 °, 23.30 ± 0.2 °, 24.11 ± 0.2 °, 25.40 ± 0.2 °, 27.12 ±
There is characteristic diffraction peak at 0.2 °, 29.18 ± 0.2 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,48.66,21.72,
60.30,76.51,67.64,47.33,50.94.As shown in Fig. 3.X-ray powder diffraction test condition: Holland
EMPYREAN (sharp shadow) X-ray diffractometer of Panalytical company, CuK α radiation, light pipe voltage 40kV, heater current
300mA, continuous scanning, 0.02 ° of step-length, 8 °/min of scanning speed, scanning range is 2~50 °.
1/20 water Ribavirin compound of the present invention, dsc analysis is the results show that have heat absorption at about 172.0 DEG C
There is exothermic peak at peak at about 270.8 DEG C.As shown in Fig. 4.DSC data is by heat analysis-mass spectrometer (NETZSCH STA
449C) analysis obtains, analysis condition are as follows: 2~10mg of sample, alumina crucible, high pure nitrogen do reaction gas and protection gas, flow
Respectively 40ml/min and 30ml/min.10 DEG C/min of heating rate, 25~400 DEG C of temperature range.
Further purpose of the invention provides a kind of pharmaceutical composition containing 1/20 water Ribavirin compound.It is excellent
Selection of land, described pharmaceutical composition include 1/20 water Ribavirin compound and the excipient pharmaceutically received.It is highly preferred that drug
Composition is selected from pharmaceutically acceptable dosage form.
Detailed description of the invention
The TG analysis chart of 1/20 water Ribavirin compound of Fig. 1.
The FTIR spectrum figure of 1/20 water Ribavirin compound of Fig. 2.
The x-ray diffractogram of powder of 1/20 water Ribavirin compound of Fig. 3 is composed.
The dsc analysis figure of 1/20 water Ribavirin compound of Fig. 4.
Specific embodiment
Below will by specific embodiment, the present invention will be further described, but therefore do not limit the present invention to institute
In the scope of embodiments stated, it should be understood by those skilled in the art that changing to the equivalent replacement that the content of present invention is done, or accordingly
Into still falling within protection scope of the present invention.
The preparation of embodiment 1:1/20 water Ribavirin compound
1000ml water is added in container, temperature is controlled at 50 DEG C, 100.06g Ribavirin crude product is added, stir molten
Solution adds 1.02g active carbon with disodium hydrogen phosphate and sodium dihydrogen phosphate control pH value 5.0, and stirring and adsorbing is decolourized 30min,
Decompression filters, and rinses filter cake with 50ml water, filtrate is taken to be added in reaction kettle, reduces temperature to 15 DEG C, is slowly added to acetonitrile
1000ml stands crystallization 2h, and decompression filters, and filter cake is washed with acetonitrile 50ml, and 40 DEG C are dried under reduced pressure 2h, obtain 1/20 water Ribavirin
Compound 92.62g.
As a result:
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 11.97 °, 13.45 °, 18.22 °, 23.30 °, 24.11 °,
There is characteristic diffraction peak at 25.40 °, 27.12 °, 29.18 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,48.66,21.72,
60.30,76.51,67.64,47.33,50.94.
Infrared spectroscopy is 3451.7cm in wave number-1, 3349.1cm-1, 2955.6cm-1, 1663.3cm-1, 1502.8cm-1,
1438.4cm-1, 1362.1cm-1, 1234.6cm-1, 1070.6cm-1, 958.7cm-1, 836.6cm-1, 773.2cm-1There is feature at place
Absorption peak.
It is 99.86% that HPLC method, which detects purity,；It is 0.38% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.34%, it is almost the same with the result (theoretical value 0.37%) of 1/20 water contained in this way；Elemental Analysis theory are as follows: C:
39.20%, H:4.98%, N:22.86%, O:32.96%；Measured value are as follows: C:39.18%, H:4.96%, N:22.89%, O:
32.97%.
The preparation of embodiment 2:1/20 water Ribavirin compound
1000ml water is added in container, temperature is controlled at 55 DEG C, 100.14g Ribavirin crude product is added, stir molten
Solution adds 1.05g active carbon with disodium hydrogen phosphate and sodium dihydrogen phosphate control pH value 6.0, and stirring and adsorbing is decolourized 30min,
Decompression filters, and rinses filter cake with 50ml water, filtrate is taken to be added in reaction kettle, reduces temperature to 10 DEG C, is slowly added to acetonitrile
1000ml stands crystallization 4h, and decompression filters, and filter cake is washed with acetonitrile 50ml, and 50 DEG C are dried under reduced pressure 1.5h, obtain 1/20 water conservancy Ba Wei
Woods compound 93.35g.
As a result:
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 11.94 °, 13.46 °, 18.25 °, 23.32 °, 24.12 °,
There is characteristic diffraction peak at 25.43 °, 27.14 °, 29.19 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,47.23,20.85,
61.54,77.19,65.46,46.07,51.25.
Infrared spectroscopy is 3451.3cm in wave number-1, 3349.0cm-1, 2955.8cm-1, 1663.5cm-1, 1502.6cm-1,
1438.9cm-1, 1362.0cm-1, 1234.2cm-1, 1070.4cm-1, 958.8cm-1, 836.5cm-1, 773.4cm-1There is feature at place
Absorption peak.
It is 99.82% that HPLC method, which detects purity,；It is 0.32% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.33%, it is almost the same with the result (theoretical value 0.37%) of 1/20 water contained in this way；Elemental Analysis theory are as follows: C:
39.20%, H:4.98%, N:22.86%, O:32.96%；Measured value are as follows: C:39.19%, H:4.98%, N:22.88%, O:
32.95%.
The preparation of embodiment 3:1/20 water Ribavirin compound
1000ml water is added in container, temperature is controlled at 60 DEG C, 100.02g Ribavirin crude product is added, stir molten
Solution adds 1.01g active carbon with disodium hydrogen phosphate and sodium dihydrogen phosphate control pH value 5.5, and stirring and adsorbing is decolourized 30min,
Decompression filters, and rinses filter cake with 50ml water, filtrate is taken to be added in reaction kettle, reduces temperature to 20 DEG C, is slowly added to acetonitrile
1000ml stands crystallization 3h, and decompression filters, and filter cake is washed with acetonitrile 50ml, and 60 DEG C are dried under reduced pressure 1h, obtain 1/20 water Ribavirin
Compound 91.82g.
As a result:
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 11.94 °, 13.44 °, 18.21 °, 23.32 °, 24.12 °,
There is characteristic diffraction peak at 25.44 °, 27.15 °, 29.17 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,49.24,22.75,
58.68,73.70,65.45,46.12,48.77.
Infrared spectroscopy is 3451.8cm in wave number-1, 3349.3cm-1, 2955.8cm-1, 1663.5cm-1, 1502.7cm-1,
1438.2cm-1, 1362.4cm-1, 1234.5cm-1, 1070.6cm-1, 958.8cm-1, 836.3cm-1, 773.0cm-1There is feature at place
Absorption peak.
It is 99.83% that HPLC method, which detects purity,；It is 0.43% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.40%, it is almost the same with the result (theoretical value 0.37%) of 1/20 water contained in this way；Elemental Analysis theory are as follows: C:
39.20%, H:4.98%, N:22.86%, O:32.96%；Measured value are as follows: C:39.20%, H:4.96%, N:22.85%, O:
32.99%.
Comparative example 1 prepares Ribavirin compound according to existing technical literature CN 101891786A
Using the patent Example 1 and the identical method of embodiment 2
Preparation method:
1- (2,3,5- tri- -0- acetyl group-β-D-RIBOSE base) -1H-1, the synthesis of 2,4- triazole -3- carboxylate methyl esters
In the there-necked flask equipped with thermometer and churned mechanically 2000ml, 318.03g (1mol) 1,2,3,5-Tetra-O-Acetyl-D-Ribose is added,
The triazole methyl esters of 127.10g (1mol), 20.06g trifluoromethanesulfonic acid are put into microwave reactor, and power 400W, heating is arranged
To 55 DEG C, insulation reaction 60min is cooled to room temperature, and 1000ml methanol is added, and is dissolved by heating, is poured out, and is precipitated after cooling a large amount of white
Color solid filters, and washs, dry, obtains 1- (2,3,5- tri- -0- acetyl group-β-D-RIBOSE base) -1H-1,2,4- triazole -3-
Carboxylate methyl ester 346.92g.
The synthesis of Ribavirin
1- (2,3, the 5- tri- -0- acetyl group-β-D-RIBOSE of 191.05g (0.5mol) are added in a high pressure reaction kettle
Base) -1H-1, the methanol of 2,4- triazole -3- carboxylate methyl esters and 2000ml, being passed through nitrogen at room temperature makes reaction kettle keep 2kg's
Pressure reacts 5h, then recycles extra ammonia, and solvent is removed under reduced pressure, and residue ethyl alcohol recrystallization obtains Ribavirin production
Product 107.52g
It is 99.63% that HPLC method, which detects purity,；It is 0.22% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.23%；Elemental Analysis theory are as follows: C:39.35%, H:4.95%, N:22.94%, O:32.76%；Measured value are as follows: C:
39.38%, H:4.94%, N:22.92%, O:32.76%.
Comparative example 2 prepares Ribavirin compound according to existing technical literature CN 102127134A
Using the identical method of patent Example 2
Preparation method:
(1) 100.03g Ribavirin crude product is dissolved in 2000ml purified water, is slowly added to 10% benzoic acid solution, stirs
Reaction is mixed, precipitating is generated, Ribavirin benzoate solid is obtained by filtration.
(2) Ribavirin benzoate solid is dissolved in the mixing of acetonitrile and methylene chloride that 2000ml volume ratio is 2:3
In solvent, 3.00g active carbon, 60 DEG C of stirring 20min is added, filtering decarbonization collects filtrate.
(3) it is for the acetonitrile of 2:3 and the mixed solvent of methylene chloride with volume ratio by chromatography column separating purification by filtrate
Mobile phase, fixed phase stuffing are silica gel, and flow velocity 4.5ml/min, collects filtrate by 30 DEG C of column temperature.
(4) 8% sodium bicarbonate solution is added into filtrate, solid is gradually precipitated, then keeps the temperature and sufficiently stir in 60 DEG C of decompression stirrings
Reaction 2h is mixed, filtering, water washing, 60 DEG C are dried under reduced pressure, and obtain Ribavirin 90.16g.
It is 99.29% that HPLC method, which detects purity,；It is 0.25% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.27%；Elemental Analysis theory are as follows: C:39.35%, H:4.95%, N:22.94%, O:32.76%；Measured value are as follows: C:
39.35%, H:4.93%, N:22.92%, O:32.80%.
1 study on the stability of test example
The Ribavirin compound that the present inventor prepares embodiment 1, comparative example 1, comparative example 2 has carried out stability and has examined
It examines.Temperature is 40 DEG C ± 2 DEG C, is placed 6 months, is sampled respectively at 0,1,2,3,6 the end of month.Inspection target be character, solution it is clear
Clear degree and color, moisture, content and related substance.
As a result: can be seen that by accelerated test result, significant change, comparative example 1 do not occur for the moisture of the embodiment of the present invention 1
It is substantially reduced with the moisture of comparative example 2, can further infer that sample contained humidity prepared by the present embodiment 1 is the crystallization water；This hair
Other every Testing index of bright embodiment 1 are also significantly better than comparative example 1 and comparative example 2, have absolutely proved prepared by the present invention
1/20 water Ribavirin compound stability is more preferable, and quality is better than similar product.
The freeze-drying test of test example 2
The Ribavirin compound that the present inventor prepares embodiment 1, comparative example 1, comparative example 2 is freeze-dried.
Ribavirin compound prepared by embodiment 1, comparative example 1, comparative example 2 is sub-packed in cillin bottle with 0.25g/ bottles, is placed in
Freeze drier, under vacuum condition -40 DEG C of dryings for 24 hours, the moisture variation of detection freeze-drying front and back.
As a result as follows:
Conclusion: moisture does not occur bright after 1/20 water Ribavirin compound prepared by the embodiment of the present invention 1 is freeze-dried
Aobvious variation, Ribavirin compound moisture prepared by comparative example 1, comparative example 2 are substantially reduced, and can speculate Ribavirin of the present invention
Closing the moisture in object is the crystallization water, and the moisture in comparative example 1,2 Ribavirin of comparative example is absorption water.
3 tabletting stability of test example
The Ribavirin compound that the present inventor prepares embodiment 1, comparative example 1, comparative example 2 is pressed into tablet press machine
The circular piece of 0.5g/ piece carries out acceleration investigation.Temperature is 40 DEG C ± 2 DEG C, places 6 months, takes respectively at 0,1,2,3,6 the end of month
Sample.Inspection target is moisture.
Conclusion: the tablet accelerated test moisture of 1/20 water Ribavirin compound compacting prepared by the embodiment of the present invention 1 is not
Significant change occurs, comparative example 1, the tablet moisture that the Ribavirin compound of comparative example 2 is suppressed are substantially reduced, and can reason out this
Moisture in invention Ribavirin compound is the crystallization water, and the moisture in comparative example 1,2 Ribavirin of comparative example is absorption water.
Claims (4)
1. a kind of 1/20 water Ribavirin compound, which is characterized in that every mole of Ribavirin contains 1/20 mole of water, and molecular formula is
C8H12N4O5·1/20H2O, molecular weight 245.11, structural formula is as follows:
2. a kind of pharmaceutical composition, it is characterised in that include 1/20 water Ribavirin compound described in claim 1.
3. a kind of pharmaceutical composition, it is characterised in that include 1/20 water Ribavirin compound described in claim 1 and pharmacy
The excipient of upper receiving.
4. pharmaceutical composition according to claim 3, it is characterised in that described pharmaceutical composition is selected from pharmaceutically acceptable
Dosage form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710709626.3A CN109134566A (en) | 2017-08-18 | 2017-08-18 | A kind of 1/20 water Ribavirin compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710709626.3A CN109134566A (en) | 2017-08-18 | 2017-08-18 | A kind of 1/20 water Ribavirin compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109134566A true CN109134566A (en) | 2019-01-04 |
Family
ID=64803345
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710709626.3A Withdrawn CN109134566A (en) | 2017-08-18 | 2017-08-18 | A kind of 1/20 water Ribavirin compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109134566A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109134565A (en) * | 2017-08-15 | 2019-01-04 | 李双喜 | 1/10 water Ribavirin compound of one kind and its pharmaceutical composition |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1535277A (en) * | 2001-07-30 | 2004-10-06 | �����ﰲ�ط���������ѧ(�����)�ɷ��� | Process for preparation of L-ribavirin |
| JP2008222630A (en) * | 2007-03-12 | 2008-09-25 | Permachem Asia Ltd | PRODUCTION METHOD OF R-II TYPE CRYSTAL OF 1-beta-D-RIBOFURANOSYL-1,2,4-TRIAZOLE-3-CARBOXAMIDE |
| CN101891786A (en) * | 2010-08-04 | 2010-11-24 | 王明 | Ribavirin compound and new preparation method thereof |
| CN102532226A (en) * | 2010-12-15 | 2012-07-04 | 上海迪赛诺医药发展有限公司 | Ribavirin crystal form and preparation method thereof |
| CN105483189A (en) * | 2016-01-28 | 2016-04-13 | 天津科技大学 | Preparation method of ribavirin |
| CN105693793A (en) * | 2016-03-22 | 2016-06-22 | 湖北美林药业有限公司 | Ribavirin compound and drug composition of ribavirin compound |
| CN109134565A (en) * | 2017-08-15 | 2019-01-04 | 李双喜 | 1/10 water Ribavirin compound of one kind and its pharmaceutical composition |
| CN109160930A (en) * | 2017-08-18 | 2019-01-08 | 郝志艳 | An a kind of water Troxerutin compound |
-
2017
- 2017-08-18 CN CN201710709626.3A patent/CN109134566A/en not_active Withdrawn
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1535277A (en) * | 2001-07-30 | 2004-10-06 | �����ﰲ�ط���������ѧ(�����)�ɷ��� | Process for preparation of L-ribavirin |
| JP2008222630A (en) * | 2007-03-12 | 2008-09-25 | Permachem Asia Ltd | PRODUCTION METHOD OF R-II TYPE CRYSTAL OF 1-beta-D-RIBOFURANOSYL-1,2,4-TRIAZOLE-3-CARBOXAMIDE |
| CN101891786A (en) * | 2010-08-04 | 2010-11-24 | 王明 | Ribavirin compound and new preparation method thereof |
| CN102532226A (en) * | 2010-12-15 | 2012-07-04 | 上海迪赛诺医药发展有限公司 | Ribavirin crystal form and preparation method thereof |
| CN105483189A (en) * | 2016-01-28 | 2016-04-13 | 天津科技大学 | Preparation method of ribavirin |
| CN105693793A (en) * | 2016-03-22 | 2016-06-22 | 湖北美林药业有限公司 | Ribavirin compound and drug composition of ribavirin compound |
| CN109134565A (en) * | 2017-08-15 | 2019-01-04 | 李双喜 | 1/10 water Ribavirin compound of one kind and its pharmaceutical composition |
| CN109160930A (en) * | 2017-08-18 | 2019-01-08 | 郝志艳 | An a kind of water Troxerutin compound |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109134565A (en) * | 2017-08-15 | 2019-01-04 | 李双喜 | 1/10 water Ribavirin compound of one kind and its pharmaceutical composition |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2016343633B2 (en) | Valbenazine salts and polymorphs thereof | |
| CN101220068B (en) | A set of geldanamycin derivant and method for preparing the same | |
| US10669300B2 (en) | Methods of separating gemcitabine-phosphate diastereoisomers | |
| EP2308886B1 (en) | Process for the production of a spiroketal derivative | |
| CN109134566A (en) | A kind of 1/20 water Ribavirin compound | |
| CN109160930A (en) | An a kind of water Troxerutin compound | |
| CN109134500A (en) | A kind of 1/2 water cefradine compound | |
| CN109134565A (en) | 1/10 water Ribavirin compound of one kind and its pharmaceutical composition | |
| CN113603721B (en) | Method for synthesizing SAICAR | |
| CN113683653B (en) | Adenosine crystal form, preparation method and application thereof | |
| CN115260053A (en) | Compound with antitumor activity and preparation method and application thereof | |
| CN109134581A (en) | Three water dexamethasone sodium phosphate compounds of one kind and its drug combination preparation | |
| CN109134501A (en) | 1/5 water cefradine compound of one kind and its drug combination preparation | |
| CN104163771A (en) | Preparation method of Agomelatine crystal form I | |
| CN112939876A (en) | Crystal form I of Mavacamten and preparation method thereof | |
| CN109096306A (en) | A kind of 1/2 water Cefazolin sodium compound | |
| CN113045554A (en) | Fexotinib crystal form and preparation method thereof | |
| CN113880872A (en) | Preparation of camptothecin boric acid compound and application of camptothecin boric acid compound in anti-tumor aspect | |
| CN108324717B (en) | Application of pivaloylchlorobenzo [ d ] aza-quinazoline compound in preparation of drugs for treating cervical cancer | |
| CN108125962B (en) | Application of benzo [ d ] aza-quinazoline compound in preparation of drugs for treating lung cancer | |
| CN109336937A (en) | A kind of preparation method of Ribavirin | |
| CN109081848B (en) | A kind of 1/4 water Cefazolin sodium compound | |
| CN113234027B (en) | 4, 6-bis (aryloxy) pyrimidine derivative and synthesis method and application thereof | |
| CN109081847A (en) | A kind of 1/2 water cefotaxime sodium compound | |
| CN103508920A (en) | Preparation method for optical isomers of phenylalaninol compound and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20190104 |