CN109134565A - 1/10 water Ribavirin compound of one kind and its pharmaceutical composition - Google Patents
1/10 water Ribavirin compound of one kind and its pharmaceutical composition Download PDFInfo
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- CN109134565A CN109134565A CN201710695223.8A CN201710695223A CN109134565A CN 109134565 A CN109134565 A CN 109134565A CN 201710695223 A CN201710695223 A CN 201710695223A CN 109134565 A CN109134565 A CN 109134565A
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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
- C07H19/056—Triazole or tetrazole radicals
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Abstract
The invention discloses a kind of 1/10 water Ribavirin compound and its pharmaceutical composition, every mole of Ribavirin compound contains 1/10 mole of water.Its infrared spectroscopy is 3451.8 ± 2cm in wave number‑1, 3347.5 ± 2cm‑1, 2857.1 ± 2cm‑1, 1663.3 ± 2cm‑1, 1502.8 ± 2cm‑1, 1438.4 ± 2cm‑1, 1336.8 ± 2cm‑1, 1281.8 ± 2cm‑1, 1070.3 ± 2cm‑1, 892.8 ± 2cm‑1, 773.3 ± 2cm‑1, 672.0 ± 2cm‑1There is characteristic absorption peak at place.The present invention is by influencing the factor investigation of crystallization and the research of different crystallization solvent systems on Ribavirin, purity is high, 1/10 water Ribavirin compound of stability are prepared, and the good pharmaceutical composition of stability is prepared by 1/10 water Ribavirin compound of the present invention.
Description
Technical field
The invention belongs to chemical engineering medicine crystallization technique fields, are related to 1/10 water Ribavirin compound of one kind and its medicine
Compositions.
Background technique
Ribavirin is also known as the happy star of ribavirin, virazole, prestige, triazole nucleoside, amide triazole nucleoside, is a kind of non-choosing
Selecting property ucleosides broad-spectrum antiviral drug belongs to monophosphate inosine (IMP) dehydrogenase inhibitor, bird is participated in human body
Purine metabolism interferes the biosynthesis of guanine, prevents the duplication of virus, has inhibiting effect to a variety of DNA and RNA virus.
Viral pneumonia caused by the clinical treatment infection of the upper respiratory tract, Respiratory Syncytial Virus(RSV) and bronchitis, influenza, rubeola, blister
Rash, rotavirus enteritis, children's early stage adenovirus pneumonia psoriasis etc. have special efficacy, and Epidemic Hemorrhagic Fever, hepatitis B, hepatitis A also have centainly
Curative effect.
Existing technology, which prepares Ribavirin, following three kinds of methods.
(1) chemical method:
Guanosine and guanylic acid are hydrolyzed under the action of glacial acetic acid and aceticanhydride first, generate ribose -1- phosphoric acid, then double-right
Under the catalysis of nitrophenol, reacted with three nitrine contracting amides and generate condensation product, through ammonolysis to obtain the final product.
(2) fermentation method:
In nucleosides, D-ribose or D-Glucose culture medium, 1,2,4- triazole -3- carboxylic acid amides and strain, room temperature is added
It cultivates up to Ribavirin.
(3) enzymatic method:
Guanosine and guanylic acid are hydrolyzed under the action of pyrimidine-nucleoside phosphorylase first, generate ribose -1- phosphoric acid, then fast
It is reacted under the action of purine nucleoside phosphorylase with three nitrine carboxylic acid amides and directly generates Ribavirin.
But the Ribavirin of existing technology preparation haves the shortcomings that stability is poor, and the stability of raw material is to preparation
Stability and drug safety and the performance of enterprises are significant, and the present inventor prepares a kind of purity is high, and stability is good
Ribavirin compound, and simple production process, it is easily operated, it is at low cost, it is suitble to industrialized production.And by of the present invention
Ribavirin compound prepares the good pharmaceutical composition of stability.
Summary of the invention
The invention discloses the new solvates of one kind of Ribavirin, are more specifically 1/10 water Ribavirin chemical combination
Object, i.e. every mole of Ribavirin compound contain 1/10 mole of water, molecular formula C8H12N4O5·1/10H2O, molecular weight 246.01,
Structural formula is as follows:
1/10 water Ribavirin compound of the present invention, preparation the following steps are included:
Ribavirin crude product is added in water and the mixed solution of n,N-Dimethylformamide under normal temperature condition, is stirred molten
Active carbon is added in solution, and stirring and adsorbing filters carbon removal, rinses filter cake with n,N-Dimethylformamide, controls filtrate temperature, uses
10% aqueous sodium carbonate adjusts pH, and portions of ether and methyl alcohol mixed liquor is first added, and stands crystallization, reduces temperature, adds second
Ether and methyl alcohol mixed liquor stirring and crystallizing, are filtered under diminished pressure, and rinse filter cake with ether and methyl alcohol mixed liquor, are dried under reduced pressure, obtain 1/10 water
Ribavirin compound.
Preferably, in above-mentioned preparation method, the volume ratio of the water and n,N-Dimethylformamide is (0.5~3): 1, more
Preferably, the volume ratio of water and n,N-Dimethylformamide is (1~2): 1.
Preferably, in above-mentioned preparation method, the crystallization temperature for the first time is 10~40 DEG C, it is highly preferred that crystallization temperature for the first time
Degree is 20~30 DEG C.
Preferably, in above-mentioned preparation method, the adjusting pH value is 6~10, it is highly preferred that adjusting pH value is 7~9.
Preferably, in above-mentioned preparation method, the volume ratio of the ether and methanol is (2~5): 1, it is highly preferred that ether
Volume ratio with methanol is (3~4): 1.
Preferably, in above-mentioned preparation method, the secondary crystallization temperature is -10~20 DEG C, it is highly preferred that secondary crystallization temperature
Degree is 0~10 DEG C.
Preferably, in above-mentioned preparation method, the secondary crystallization time is 1~3h, it is highly preferred that the secondary crystallization time is
1.5~2.5h
Preferably, in above-mentioned preparation method, the drying temperature be 40~70 DEG C, it is highly preferred that drying temperature be 50~
60℃。
Preferably, in above-mentioned preparation method, the drying time is 2~5h, it is highly preferred that drying time is 3~4h.
Karl_Fischer method be containing one of the most single-minded, accurate method in moisture method in various measurement substances, by
It is classified as the basic skills of determination of moisture in many substances, especially to organic compound, as a result accurately and reliably.It is disclosed by the invention
Ribavirin compound Karl_Fischer method measures moisture content between 0.67%~0.78%, and theoretical moisture content is
0.73%, it may be determined that Ribavirin compound of the present invention contains 1/10 water.
1/10 water Ribavirin compound of the present invention, TG are analyzed the results show that according to the weightless percentage of TG line
Rate calculated result is it is found that weightlessness about 0.70%, and the theoretical percentage composition of water is 0.73% in Ribavirin molecule, referring to taking Xiu Shi
It is 0.67%~0.78% that method, which measures Ribavirin moisture content, and it is 0.70% that experiment, which measures TG weightlessness, with theoretical water content
Substantially it is consistent.It can be inferred that Ribavirin TG weightlessness is caused by removing water, and every mole of Ribavirin contains 1/10 mole of water.Such as
Shown in attached drawing 1.Data are obtained by heat analysis-mass spectrometer (NETZSCH STA 449C) analysis.Analysis condition are as follows: sample 2
~10mg, alumina crucible, high pure nitrogen do reaction gas and protection gas, and flow is respectively 40ml/min and 30ml/min, heating
Rate 10K/min, temperature test range are 25~400 DEG C.Sample decomposition temperature is about 254.7 DEG C.
1/10 water Ribavirin compound of the present invention, infrared spectroscopy are 3451.8 ± 2cm in wave number-1,
3347.5±2cm-1, 2857.1 ± 2cm-1, 1663.3 ± 2cm-1, 1502.8 ± 2cm-1, 1438.4 ± 2cm-1, 1336.8 ±
2cm-1, 1281.8 ± 2cm-1, 1070.3 ± 2cm-1, 892.8 ± 2cm-1, 773.3 ± 2cm-1, 672.0 ± 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.
1/10 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 °, 15.61 ± 0.2 °, 18.22 ± 0.2 °, 23.30 ± 0.2 °, 24.11 ± 0.2 °, 25.40 ±
There is characteristic diffraction peak at 0.2 °, 27.11 ± 0.2 °, 29.18 ± 0.2 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,
48.49,15.06,22.15,69.27,84.58,77.36,48.22,54.35.As shown in Fig. 3.X-ray powder diffraction test
Condition: EMPYREAN (sharp shadow) X-ray diffractometer of Dutch Panalytical company, CuK α radiation, light pipe voltage 40kV, lamp
Silk electric current 300mA, continuous scanning, 0.02 ° of step-length, 8 °/min of scanning speed, scanning range is 2~50 °.
1/10 water Ribavirin compound of the present invention, dsc analysis is the results show that have heat absorption at about 171.8 DEG C
There is exothermic peak at peak at about 270.6 DEG C.As shown in Fig. 4.DSC data is by heat analysis-mass spectrometer (NETZSCH
STA449C) analysis obtains, analysis condition are as follows: and 2~10mg of sample, alumina crucible, high pure nitrogen do reaction gas and protection gas,
Flow is 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 1/10 water Ribavirin compound.It is excellent
Selection of land, described pharmaceutical composition include 1/10 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
Fig. 1 is that the TG of 1/10 water Ribavirin compound is analyzed.
Fig. 2 is the FTIR spectrum figure of 1/10 water Ribavirin compound.
Fig. 3 is that the x-ray diffractogram of powder of 1/10 water Ribavirin compound is composed.
Fig. 4 is the dsc analysis figure of 1/10 water Ribavirin compound.
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 1 1/10 water Ribavirin compound of embodiment
600ml (the volume ratio of water and N,N-dimethylformamide is added in lower Ribavirin crude product 80.15g of normal temperature condition
For in 1:1) mixed solution, active carbon 0.62g, stirring and adsorbing 20min is added in stirring and dissolving, carbon removal is filtered, with 50mlN, N- bis-
Methylformamide rinses filter cake, and control filtrate temperature is 20 DEG C, and adjusting pH value with 10% aqueous sodium carbonate is 7.0, is first added
The volume ratio of ether and methanol be 3:1 mixed liquor 200ml, stand crystallization 0.5h, reduce temperature to 0 DEG C, add ether with
The volume ratio of methanol is the mixed liquor 400ml stirring and crystallizing 1.5h of 3:1, is filtered under diminished pressure, is with 50ml ether and methanol volume ratio
The mixed liquor of 3:1 rinses filter cake, and 50 DEG C are dried under reduced pressure 4h, obtain 1/10 water Ribavirin compound 92.12g.
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 11.97 °, 13.45 °, 15.61 °, 18.22 °, 23.30 °,
There is characteristic diffraction peak at 24.11 °, 25.40 °, 27.11 °, 29.18 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,
48.49,15.06,22.15,69.27,84.58,77.36,48.22,54.35.
Infrared spectroscopy is 3451.8cm in wave number-1, 3347.5cm-1, 2857.1cm-1, 1663.3cm-1, 1502.8cm-1,
1438.4cm-1, 1336.8cm-1, 1281.8cm-1, 1070.3cm-1, 892.8cm-1, 773.3cm-1, 672.0cm-1There is feature at place
Absorption peak.
It is 99.75% that HPLC method, which detects purity,；It is 0.72% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.70%, it is almost the same with the result (theoretical value 0.73%) of 1/10 water contained in this way；Elemental Analysis theory are as follows: C:
39.06%, H:5.00%, N:22.77%, O:33.17%；Measured value are as follows: C:39.08%, H:5.03%, N:22.74%, O:
33.15%.
The preparation of 2 1/10 water Ribavirin compound of embodiment
600ml is added in lower Ribavirin crude product 80.07g of normal temperature condition, and (water is with N,N-dimethylformamide volume ratio
2:1) in mixed solution, active carbon 0.61g, stirring and adsorbing 20min is added in stirring and dissolving, carbon removal is filtered, with 50mlN, N- diformazan
Base formamide rinses filter cake, and control filtrate temperature is 30 DEG C, and adjusting pH value with 10% aqueous sodium carbonate is 9.0, and second is first added
The mixed liquor 200ml that ether and methanol volume ratio are 4:1, stands crystallization 0.5h, reduces temperature to 10 DEG C, adds ether and methanol
Volume ratio is the mixed liquor 400ml stirring and crystallizing 2.5h of 4:1, is filtered under diminished pressure, and is the mixed of 4:1 with 50ml ether and methanol volume ratio
It closes liquid and rinses filter cake, 60 DEG C are dried under reduced pressure 3h, obtain 1/10 water Ribavirin compound 93.71g.
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 11.95 °, 13.46 °, 15.62 °, 18.23 °, 23.34 °,
There is characteristic diffraction peak at 24.13 °, 25.42 °, 27.15 °, 29.16 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,
47.55,16.18,21.27,68.70,82.53,77.69,48.35,53.27.
Infrared spectroscopy is 3451.7cm in wave number-1, 3347.5cm-1, 2857.3cm-1, 1663.4cm-1, 1502.9cm-1,
1438.6cm-1, 1336.5cm-1, 1281.7cm-1, 1070.2cm-1, 892.5cm-1, 773.0cm-1, 672.4cm-1There is feature at place
Absorption peak.
It is 99.77% that HPLC method, which detects purity,；It is 0.78% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.75%, it is almost the same with the result (theoretical value 0.73%) of 1/10 water contained in this way；Elemental Analysis theory are as follows: C:
39.06%, H:5.00%, N:22.77%, O:33.17%；Measured value are as follows: C:39.05%, H:5.00%, N:22.74%, O:
33.21%.
The preparation (specification: 1ml:100mg) of 3 1/10 water Ribavirin compound medicine composition of embodiment
Prescription:
| 1/10 water Ribavirin compound | 100g |
| Water for injection | Add to 1000ml |
| It is made | 1000 |
Preparation method: taking 800ml water for injection, and 1/10 water Ribavirin compound stirring and dissolving of recipe quantity is added, adds
Water for injection is stirred evenly to full dose；0.1% (g/ml) medicinal carbon is added, stirs 30 minutes, 0.45 μm of filter membrane carbon removal,
0.22 μm of filter membrane refined filtration measures intermediate product pH value of solution, content, determines that loading amount is sub-packed in ampoule bottle by specification, 121 DEG C after sealing
Moist heat sterilization 15min.
The preparation (specification: 2ml:250mg) of 4 1/10 water Ribavirin compound medicine composition of embodiment
Prescription:
| 1/10 water Ribavirin compound | 125g |
| Water for injection | Add to 1000ml |
| It is made | 1000 |
Preparation method: taking 800ml water for injection, and 1/10 water Ribavirin compound stirring and dissolving of recipe quantity is added, adds
Water for injection is stirred evenly to 1000ml；0.1% (g/ml) medicinal carbon is added, stirs 30 minutes, 0.45 μm of filter membrane removes
Charcoal, 0.22 μm of filter membrane refined filtration degerming measure intermediate product pH value of solution, content, determine that loading amount is sub-packed in ampoule bottle by specification, seal
121 DEG C of moist heat sterilization 15min afterwards.
Comparative example 1 prepares Ribavirin compound according to 1535278 A of existing technical literature CN
Using the identical method of the patent Example
Preparation process:
The synthesis of 1- (tri--O- acetyl group-β of 2,3,5--D-RIBOSE base) -1H-1,2,4- triazole -3- carboxylate methyl ester
1680ml is added in the 4 neck anhydrous response devices for being equipped with the 6000ml of thermometer, condenser and mechanical agitator
The tetra-acetylated ribose of methylene chloride, 400.05g and 185.21g3- carbomethoxy triazole, while stirring and being passed through nitrogen.By the mixing
Object is cooled to about 5 DEG C and 360.03g tin tetrachloride is added in the suspension in the form of thread, stirs, passes through simultaneously
It is cooled with an ice bath and controls the exothermic heat of reaction to make temperature be no more than 15-20 DEG C, and after being added completely into, it is mixed to heat the reaction
Object is closed to the 2h that flows back, 20 DEG C is allowed to cool to water and ice bath in 15min, is then added at+20 DEG C of temperature below
30% hydrochloric acid (176.7ml) and water (1503.3ml) simultaneously stir 45min；Mixture 15min is placed to be layered, is then made
The water-soluble liquid phase of layer is separated with the organic phase of enrichment, is then handled this with 30% hydrochloric acid (176.7ml) and water (1503.3ml) and is had
Machine phase.After stirring 45min, which is placed into 15min to separate each phase, by the organic phase of the water phase on top and enrichment
Separation, then handles the organic phase with 30% hydrochloric acid (176.7ml) and water (1503.3ml), after stirring 45min, by mixture
Placing 15min, phases were separated to be layered: distilling the organic phase (45 DEG C of interior temperature) under atmospheric pressure and adds to the oil residue
Enter 3000ml toluene, it is a kind of humid pasta capable of stirring that the mixture is distilled under the vacuum of about 200mbar residual gas pressure.
It is allowed to cool to 5-10 DEG C of 2h and filters on a Buchner funnel while being washed with toluene.Obtain 521.36g damp product.
The synthesis of 1- β--3 carboxylate methyl ester of D-RIBOSE base -1H-1,2,4- triazole
2000ml methanol is added into the moist solids residue of acquisition, controls moisture 0.2% hereinafter, the cooling mixing
The 34.01g sodium methoxide in 30% methanol is added to 10 DEG C and with 30min in object.A kind of clear yellow solution is obtained, at 10 DEG C
Under, solution 3h is stirred in holding in an inert atmosphere.Then 11.40g glacial acetic acid is added and (300mbar is extremely in vacuum
The mixture is distilled under 50mbar) in 30-35 DEG C, obtains a kind of oily residue, the residue is dissolved again with methanol, true
The lower distillation of sky, obtains a kind of oily residue.
The synthesis of Ribavirin
1000ml methanol and 64.12g ammonia are added into the residue of acquisition and under stiring by the mixture 20
DEG C place 4h；Occurs the precipitating of product during reflection.(200mmHg is depressurized again；40 DEG C of internal temperature) under distillation to big
About half volume is simultaneously added to 200ml water；60-70 DEG C is heated to until dissolving and being added 400ml methanol.The cooling mixed liquor arrives
0-5 DEG C 4 hours and with the filtered on buchner funnel solid, while being washed with methanol；The Ribavirin for obtaining 302.22g humidity is thick
Product are crystallized without dry.
Crystallization
200ml water is put into 1000ml reactor and is heated to 40-50 DEG C, while 302.22g is added a little every time
Moist Ribavirin is heated to 60 DEG C of maximum temperature, while stirring until dissolution, and 500ml methanol is then added；PH value is
7.6,45 DEG C are cooled to, places 1h crystallization, while stirring at ambient temperature；5 DEG C of 2h filtered on buchner funnel are cooled to, simultaneously
It is washed with 200ml methanol, is dried overnight for 60 DEG C under vacuum, obtains 193.72g Ribavirin.
It is 99.66% that HPLC method, which detects purity,；It is 0.27% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.30%；Elemental Analysis theory are as follows: C:39.35%, H:4.95%, N:22.94%, O:32.76%；Measured value are as follows: C:
39.36%, H:4.96%, N:22.93%, O:32.75%.
Comparative example 2 prepares Ribavirin compound according to 102127134 A of existing technical literature CN
Using the identical method of patent Example 1
Preparation process:
100.02g Ribavirin crude product is dissolved in 1500ml water, 5% benzoic acid solution is slowly added to, is stirred to react, is produced
Raw precipitating, filters to obtain Ribavirin benzoate solid, and it is 2:3 that Ribavirin benzoate solid, which is dissolved in 2000ml volume ratio,
Acetonitrile and methylene chloride in the mixed solvent, be added 2.51g active carbon, 60 DEG C of stirring 30min, filtering carbon removal, filtrate is led to
Chromatography column separating purification is crossed, is the acetonitrile of 2:3 and the mixed solvent of methylene chloride as mobile phase using volume ratio, fixed phase stuffing is
Aluminium oxide, flow velocity 2.8ml/min, collect filtrate by 30 DEG C of column temperature, and 10% sodium bicarbonate solution, 60 DEG C of decompressions are added into filtrate
Stirring, is gradually precipitated solid, then keeps the temperature and reaction 1.5h is sufficiently stirred, and filtering is washed with water, 60 DEG C are dried under reduced pressure, and obtain Li Ba
Wei Lin 88.89g.
It is 99.61% that HPLC method, which detects purity,；It is 0.25% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.22%；Elemental Analysis theory are as follows: C:39.35%, H:4.95%, N:22.94%, O:32.76%；Measured value are as follows: C:
39.33%, H:4.96%, N:22.95%, O:32.76%.
1 accelerated test of test example
Under the conditions of Ribavirin compound prepared by Examples 1 to 2, comparative example 1, comparative example 2 is placed in 40 DEG C ± 2 DEG C,
Respectively in 0,1,2,3,6 month sample detection.
Test result:
Conclusion: become before and after the related substance accelerated test of 1/10 water Ribavirin compound prepared by the embodiment of the present invention 1~2
Change less, the related substance of Ribavirin compound prepared by comparative example 1, comparative example 2 accelerates to significantly increase after investigating 6 months, table
1/10 water Ribavirin compound stability prepared by the bright embodiment of the present invention 1~2 is significantly better than prior art comparative example 1, right
Ribavirin compound prepared by ratio 2.The moisture of Examples 1 to 2 infers its water contained substantially without significant change simultaneously
It is the crystallization water, and non-adsorbed water.
2 tabletting stability of test example
The Ribavirin compound that the present inventor prepares Examples 1 to 2, 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.
Test result:
Conclusion: the tablet accelerated test moisture of 1/10 water Ribavirin compound compacting prepared by the embodiment of the present invention 1~2
Substantially there is no significant change, comparative example 1, the tablet moisture that the Ribavirin compound of comparative example 2 is suppressed are substantially reduced, and show this
Moisture in 1/10 water Ribavirin compound of invention is the crystallization water, in comparative example 1,2 Ribavirin compound of comparative example
Moisture is absorption water.
The freeze-drying of test example 3 is investigated
Freeze-drying front and back is vacuumized by the way that Examples 1 to 2, comparative example 1,2 Ribavirin of comparative example are placed in freeze dryer
Moisture variation, the moisture to verify in compound are the crystallization water or absorption water, and experiment condition is: -30 DEG C of vacuum dryings
24h。
Experimental result:
| Embodiment | 0h | 48h |
| Embodiment 1 | 0.72 | 0.68 |
| Embodiment 2 | 0.78 | 0.75 |
| Comparative example 1 | 0.27 | 0.09 |
| Comparative example 2 | 0.25 | 0.11 |
Conclusion (of pressure testing): the moisture of 1/10 water Ribavirin compound of Examples 1 to 2 preparation has almost no change, and compares
Moisture in Ribavirin compound prepared by example 1, comparative example 2 is decreased obviously, and can deduce the preparation of the embodiment of the present invention 1~2
Ribavirin compound in moisture be the crystallization water, the moisture in comparative example 1,2 Ribavirin compound of comparative example is absorption
Water.
Claims (4)
1. a kind of 1/10 water Ribavirin compound, which is characterized in that every mole of Ribavirin contains 1/10 mole of water, and molecular formula is
C8H12N4O5·1/10H2O, molecular weight 246.01, structural formula is as follows:
2. a kind of pharmaceutical composition, it is characterised in that include 1/10 water Ribavirin compound described in claim 1.
3. a kind of pharmaceutical composition, it is characterised in that include 1/10 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.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109134566A (en) * | 2017-08-18 | 2019-01-04 | 樊艳芳 | A kind of 1/20 water Ribavirin compound |
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| CN1535277A (en) * | 2001-07-30 | 2004-10-06 | �����ﰲ�ط���������ѧ(�����)�ɷ��� | Process for preparation of L-ribavirin |
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