CN1429826A - Preparation method and use of sodium Penciclovir sodium hydrate - Google Patents
Preparation method and use of sodium Penciclovir sodium hydrate Download PDFInfo
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- CN1429826A CN1429826A CN 01138373 CN01138373A CN1429826A CN 1429826 A CN1429826 A CN 1429826A CN 01138373 CN01138373 CN 01138373 CN 01138373 A CN01138373 A CN 01138373A CN 1429826 A CN1429826 A CN 1429826A
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- penciclovir
- sodium
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- hydrate
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Abstract
A monohydrated Penxiluowei sodium used for preparing injection or exterior-applied medicine is prepared through dissolving Penxiluowei in the solution of sodium hydroxide, regulating pH value, adding inertial organic solvent dissolved with water, stirring, laying aside, filter, washing, and vacuum drying the deposit at 40-90 deg.C. Its advantages are low cost, high purity and high water solubility.
Description
Technical field
The present invention relates to a kind of preparation method and application of Penciclovir sodium hydrate, specifically, the pharmaceutical preparation that this hydrate is made as bulk drug (as injection, external preparation etc.) can be used for treating the disease that causes because of some Causative virus.
Background technology
Penciclovir Penciclovir, chemistry 9-[4-Hydroxy-3-(hydroxymethyl) but-1-yl by name] and guanine, molecular formula is C
10H
15N
5O
4It is potent, a purine class antiviral selectively.Herpes simplex virus I type (HSV-1) and hepatitis B virus are had obvious activity, and it is at first to be invented by people's (United States Patent (USP) 4942166,5075445) such as Michael R, and the listing of its bulk drug and preparation thereof is all arranged at present both at home and abroad.
Because this solubleness less (about 1.7mg/ml) in water of Penciclovir, the preparation pharmaceutical preparation particularly water soluble preparation need add a certain amount of solubility promoter often, too much if solubility promoter adds, then will inevitably increase the toxic side effect in the clinical use.Therefore, under the prerequisite that guarantees the Penciclovir drug effect, how to improve its solubility property, avoid clinically because of using solubility promoter to cause that toxic side effect just seems particularly important.Because penciclovir sodium and hydrate be very easily dissolving (greater than 200mg/ml, 20 ℃) in water, the trend that replaces Penciclovir is arranged greatly when the preparation aqueous solubility pharmaceutical formulations.At present preparation penciclovir sodium and hydrate thereof have the method method that prepared Penciclovir sodium water solution is carried out lyophilize or drying under reduced pressure commonly used to be prepared, but when adopting lyophilize, not only grow (often greater than 2 days) time of drying, output is lower, but also will consume a large amount of energy consumptions; When adopting drying under reduced pressure, same time of drying is longer, also needs comparatively expensive instrument simultaneously, and sample also can destroy because of long-time heating under aqueous solution state produces to decompose, and causes the finished product purity lower.
In addition, be that medical material is prepared into intravenous injection and external preparation does not appear in the newspapers as yet with Penciclovir sodium hydrate.
Summary of the invention
In view of the shortcoming and defect that the preparation method of existing penciclovir sodium and hydrate thereof exists, the object of the present invention is to provide a kind of preparation method of Penciclovir sodium hydrate, this method has easy, and is with low cost, steady quality.
A further object of the invention be with prepared Penciclovir sodium hydrate as bulk drug, make injection and other external preparation, the application in simplexvirus and the caused infection of hepatitis B virus.
In order to achieve the above object, the present invention is by the following technical solutions: Penciclovir is dissolved in the sodium hydroxide solution, the pH value 9-14 of regulator solution, under agitation add the inert organic solvents that can dissolve each other with water, place suction filtration, washing, gained is deposited in 40-90 ℃ of drying under reduced pressure to constant weight, is Penciclovir sodium hydrate (Penciclovir sodium hydrate).The inert organic solvents that described and water dissolve each other is that solvent for use can dissolve mutually with water, and not with Penciclovir or penciclovir sodium generation chemical reaction, the PH of its aqueous solution be a neutrality.
According to technical scheme of the present invention, the inert organic solvents that described and water dissolve each other is methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, acetone, butanone and acetonitrile or wherein a kind of, and the mixture that also can be wherein two kinds or they is as solvent.Penciclovir sodium-the hydrate of described preparation adds pharmaceutically acceptable carrier as bulk drug, makes intravenous formulations and external preparation, can be used for treating the scar exanthema virus and infects and the caused infection of hepatitis B virus.
The performance test of Penciclovir sodium hydrate:
1, ultimate analysis C40.75%; H5.63%; N21.80%; Na7.88% (analytical value)
C40.96%; H5.50%; N21.82%; Na7.84% (theoretical value)
The result shows that analytical value and theoretical value are (with C
10H
14N
5O
4Na.H
2The O meter) unanimity.
2, thermal weight loss and differential thermal analysis
The sample of getting by the present invention's preparation (method of embodiment one) carries out thermal weight loss and differential thermal analysis.The result, the sample of this law preparation does not have weightlessness before 80 ℃, be no free-water or volatile solvent in the sample, 80 ℃ of-120 ℃ of weightlessness about 6.4%, this with sample in to contain result's (theoretical value 6.1%) of 1 molecular crystal water consistent, differential thermal analysis result shows: this product has endotherm(ic)peak between 90-110 ℃, contains crystal water or recrystallisation solvent in the interpret sample.
3, weight loss on drying and water analysis
The sample (method of embodiment one) of the present invention's preparation is dried to constant weight at 115 ℃, and subtracting weight loss is 6.6%; Press Ka Shi aquametry mensuration moisture wherein in addition, the moisture determination result is 6.8%, two kind of unanimity as a result.Only contain moisture in this table sample, do not contain other solvent.
Comprehensive ultimate analysis, thermal weight loss and differential thermal analysis result can prove the crystal water that contains 1 molecule in the sample.
4, purity test
With reference to high-efficient liquid phase chromatogram condition and the method under relevant acyclovir (the 332nd page) inspection of Chinese Pharmacopoeia 2000 editions (two ones) item, simultaneously to checking by the sample of different technology (this law, freeze-drying and direct hypobaric drying method) preparation, the result shows, be higher than other two kinds of methods (freeze-drying and directly hypobaric drying method) by the content of the sample of this law preparation, degradation production is starkly lower than the sample of direct hypobaric drying method preparation, that is: the purity by the product of this law preparation is higher.
Compare with existing penciclovir sodium technology of preparing (freeze-drying and hypobaric drying method), advantage of the present invention is that preparation technology is simple, low production cost, and also product purity is higher, steady quality, and good water solubility, clinical safe and reliable.
Embodiment
Embodiment 1: one of preparation method of Penciclovir sodium hydrate
Get Penciclovir 2g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 11, the ethanol that under agitation adds 10 times of amounts continues to stir after 10 minutes, places 1 hour, suction filtration, add washing with alcohol 3 times (3 * 5ml), gained is deposited in 70 ℃ of drying under reduced pressure to constant weight, promptly get the 2.1g white crystalline powder.Results of elemental analyses: C40.75%; H5.63%; N21.80%; Na7.88%[penciclovir sodium-hydrate (C
10H
14N
5O
4Na.H
2O) theoretical value: C40.96%; H5.50%; N21.82%; Na7.84%].
Embodiment 2: the preparation method's of Penciclovir sodium hydrate two
Get Penciclovir 2g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 10, removes by filter insolubles, under agitation adds the methyl alcohol of 10 times of amounts, continue to stir after 10 minutes, placed 2 hours, suction filtration adds methanol wash 3 times (3 * 5ml), gained is deposited in 80 ℃ of drying under reduced pressure to constant weight, promptly gets the 1.7g white crystalline powder.
Embodiment 3: the preparation method's of Penciclovir sodium hydrate three
Get Penciclovir 2g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 12, the propyl alcohol that under agitation adds 10 times of amounts continues to stir after 10 minutes, places 2 hours, suction filtration, add propyl alcohol washing 3 times (3 * 5ml), gained is deposited in 70 ℃ of drying under reduced pressure to constant weight, promptly get the 2.1g white crystalline powder.
Embodiment 4: the preparation method's of Penciclovir sodium hydrate four
Get Penciclovir 2g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 12, the Virahol 100ml that under agitation adds 10 times of amounts continues to stir after 10 minutes, places 2 hours, suction filtration, add washed with isopropyl alcohol 3 times (3 * 5ml), gained is deposited in 90 ℃ of drying under reduced pressure to constant weight, promptly get the 2.1g white crystalline powder.
Embodiment 5: the preparation method's of Penciclovir sodium hydrate five
Get Penciclovir 2g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 11, the acetone that under agitation adds 10 times of amounts continues to stir after 10 minutes, places 2 hours, suction filtration, add washing with acetone 3 times (3 * 5ml), gained is deposited in 40 ℃ of drying under reduced pressure to constant weight, promptly get the 2.2g white crystalline powder.Results of elemental analyses: C40.83%; H5.60%; N21.91%; Na7.80%[penciclovir sodium-hydrate (C
10H
14N
5O
4Na.H
2O) theoretical value: C40.96%; H5.50%; N21.82%; Na7.84%].
Embodiment 6: the preparation method's of Penciclovir sodium hydrate six
Get Penciclovir 2g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 11, the acetonitrile that under agitation adds 5 times of amounts continues to stir after 10 minutes, places 1 hour, suction filtration, add acetonitrile washing 3 times (3 * 5ml), gained is deposited in 80 ℃ of drying under reduced pressure to constant weight, promptly get the 2.0g white crystalline powder.
Embodiment 7: the preparation method's of Penciclovir sodium hydrate seven
Get Penciclovir 2g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 11, the methyl alcohol that under agitation adds 10 times of amounts: Virahol: acetone (1: 1: 1), continue to stir after 10 minutes, placed 2 hours, suction filtration, add methyl alcohol: Virahol: acetone (1: 1: 1) washing 3 times (3 * 5ml), gained is deposited in 70 ℃ of drying under reduced pressure, promptly get the 1.7g white crystalline powder.
Embodiment 8: the preparation method's of Penciclovir sodium hydrate eight
Get Penciclovir 2g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 11, the acetone and the alcohol mixed solution (V: V=1: 1), continue to stir after 10 minutes, placed 2 hours that under agitation add 10 times of amounts, suction filtration, add washing with acetone 3 times (3 * 10ml), gained is deposited in 60 ℃ of drying under reduced pressure to constant weight, promptly get the 2.2g white crystalline powder.Results of elemental analyses: results of elemental analyses: C40.90%; H5.71%; N21.75%; Na7.76%[Penciclovir sodium hydrate (C
10H
14N
5O
4Na.H
2O) theoretical value: C40.96%; H5.50%; N21.82%; Na7.84%].
Embodiment 9: the preparation of Penciclovir sodium injection
Get Penciclovir sodium hydrate 28g, after adding injection and being diluted with water to 500ml, divide 5ml can, promptly.Specification be the 250mg Penciclovir/.Be diluted to the concentration of 1mg/ml during use with suitable transfusion, for intravenous drip.Be used for the treatment of the caused infection of herpesvirus infection and hepatitis B virus.
Embodiment 10: the preparation of Penciclovir sodium freeze-dried preparation
Get Penciclovir sodium hydrate 28g, after adding injection and being diluted with water to 250ml, divide the 2.5ml can in the 10ml cillin bottle, lyophilize promptly.Specification is 250mg Penciclovir/bottle.Be diluted to the concentration of 1mg/ml during use with suitable transfusion, for intravenous drip.
Embodiment 11: the preparation of penciclovir sodium transfusion
Get Penciclovir sodium hydrate 2.8g, sodium-chlor 22.5g (or glucose 125g) adds an amount of water for injection dissolving earlier, is diluted to 2500ml then, and can is in the 250ml infusion bottle, for intravenous drip.
Embodiment 12: the preparation of penciclovir sodium eye drops
Get Penciclovir sodium hydrate 2.8g, after adding 10ml water earlier and making solution, add an amount of isotonic regulator (as sodium-chlor, phosphate buffered saline buffer, boric acid-borate buffer solution or glucose etc.) again, reach fungistat etc., after regulating pH to 5-9, filtration sterilization, add injection and be diluted with water to 2500ml, can is in eye drop bottle, promptly.During use soup 1-2 is splashed in the eyelid.One for several times.
Embodiment 13: the preparation of penciclovir sodium externally-applied liniment
Get Penciclovir sodium hydrate 2.8g, add azone 2.5g, be dissolved in water and be diluted to 250ml, can is in the 5-20ml bottle, and specification is 1% (in Penciclovir), puts the affected part during use on the skin, and one for several times.
Embodiment 14: the preparation of penciclovir sodium ointment
Get Penciclovir sodium hydrate 2.8g, add the 247g ointment base and mix, be sub-packed in the ointment tube, specification is 1% (in Penciclovir), is coated with the affected part during use, and one for several times.
Embodiment 15: the preparation of penciclovir sodium emulsifiable paste
Get Penciclovir sodium hydrate 2.8g, add the 247g emulsifiable paste matrix and mix, be sub-packed in the ointment tube, specification is 1% (in Penciclovir), is coated with the affected part during use, and one for several times.
Embodiment 16: the preparation of Penciclovir sodium gel
Get Penciclovir sodium hydrate 2.8g, add the 247g gel matrix and mix, be sub-packed in the ointment tube, specification is 1% (in Penciclovir), is coated with the affected part during use, and one for several times.
Claims (5)
1. the preparation method of a Penciclovir sodium hydrate, this method comprises the following steps: Penciclovir is dissolved in the sodium hydroxide solution, the pH value 9-14 of regulator solution, under agitation add the inert organic solvents that can dissolve each other with water, place suction filtration, washing, gained is deposited in 40-90 ℃ of drying under reduced pressure to constant weight, is Penciclovir sodium hydrate.
2. the preparation method of a kind of penciclovir sodium-hydrate according to claim 1 is characterized in that the described inert organic solvents that dissolves each other with water is that solvent for use can dissolve mutually with water, and not with Penciclovir or penciclovir sodium generation chemical reaction.
3. according to the preparation method of the described a kind of penciclovir sodium-hydrate of claim 1, it is characterized in that the inert organic solvents that dissolves each other with water is methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, acetone, butanone and acetonitrile or wherein a kind of or their mixture.
4. the application of the described Penciclovir sodium hydrate of claim 1 in the caused infection of simplexvirus.
5, the application of the described penciclovir sodium-hydrate of claim 1 in the caused infection of hepatitis B virus.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011383739A CN1182137C (en) | 2001-12-30 | 2001-12-30 | Preparation method and use of sodium Penciclovir sodium hydrate |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011383739A CN1182137C (en) | 2001-12-30 | 2001-12-30 | Preparation method and use of sodium Penciclovir sodium hydrate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1429826A true CN1429826A (en) | 2003-07-16 |
| CN1182137C CN1182137C (en) | 2004-12-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB011383739A Expired - Fee Related CN1182137C (en) | 2001-12-30 | 2001-12-30 | Preparation method and use of sodium Penciclovir sodium hydrate |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110627793A (en) * | 2019-09-10 | 2019-12-31 | 天津理工大学 | Penciclovir and 3, 5-dihydroxy benzoic acid eutectic crystal and preparation method thereof |
| CN114380831A (en) * | 2022-01-13 | 2022-04-22 | 安徽普利药业有限公司 | Ganciclovir sodium monohydrate and preparation method thereof |
-
2001
- 2001-12-30 CN CNB011383739A patent/CN1182137C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110627793A (en) * | 2019-09-10 | 2019-12-31 | 天津理工大学 | Penciclovir and 3, 5-dihydroxy benzoic acid eutectic crystal and preparation method thereof |
| CN114380831A (en) * | 2022-01-13 | 2022-04-22 | 安徽普利药业有限公司 | Ganciclovir sodium monohydrate and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN1182137C (en) | 2004-12-29 |
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