CN1342651A - Ganciclovir sodium hydrate and its preparing process and application - Google Patents
Ganciclovir sodium hydrate and its preparing process and application Download PDFInfo
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- CN1342651A CN1342651A CN 01133524 CN01133524A CN1342651A CN 1342651 A CN1342651 A CN 1342651A CN 01133524 CN01133524 CN 01133524 CN 01133524 A CN01133524 A CN 01133524A CN 1342651 A CN1342651 A CN 1342651A
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- Prior art keywords
- ganciclovir
- sodium hydrate
- preparation
- ganciclovir sodium
- sodium
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- JJICLMJFIKGAAU-UHFFFAOYSA-M sodium;2-amino-9-(1,3-dihydroxypropan-2-yloxymethyl)purin-6-olate Chemical compound [Na+].NC1=NC([O-])=C2N=CN(COC(CO)CO)C2=N1 JJICLMJFIKGAAU-UHFFFAOYSA-M 0.000 title claims abstract description 76
- 229960002687 ganciclovir sodium Drugs 0.000 title claims abstract description 53
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Substances [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 title claims abstract description 36
- 235000011121 sodium hydroxide Nutrition 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims description 10
- 229960002963 ganciclovir Drugs 0.000 claims abstract description 25
- 238000005406 washing Methods 0.000 claims abstract description 6
- 150000002576 ketones Chemical class 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 40
- 239000000243 solution Substances 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 9
- 239000007924 injection Substances 0.000 claims description 9
- 238000013019 agitation Methods 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 238000000967 suction filtration Methods 0.000 claims description 8
- 239000003889 eye drop Substances 0.000 claims description 7
- 229940012356 eye drops Drugs 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- -1 oral preparations Substances 0.000 claims description 3
- 206010011831 Cytomegalovirus infection Diseases 0.000 claims description 2
- 208000029433 Herpesviridae infectious disease Diseases 0.000 claims description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 2
- TYHFYNTXFIAETE-UHFFFAOYSA-N O.O.[Na].N1C(N)=NC=2N=CNC2C1=O Chemical compound O.O.[Na].N1C(N)=NC=2N=CNC2C1=O TYHFYNTXFIAETE-UHFFFAOYSA-N 0.000 claims description 2
- 208000001763 cytomegalovirus retinitis Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000002672 hepatitis B Diseases 0.000 claims description 2
- 230000036737 immune function Effects 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 17
- 238000003756 stirring Methods 0.000 abstract description 8
- 239000007864 aqueous solution Substances 0.000 abstract description 3
- 238000001914 filtration Methods 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 abstract 1
- 238000001291 vacuum drying Methods 0.000 abstract 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 239000000843 powder Substances 0.000 description 8
- 238000000921 elemental analysis Methods 0.000 description 7
- 238000004108 freeze drying Methods 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 238000004455 differential thermal analysis Methods 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000004580 weight loss Effects 0.000 description 5
- 229960004150 aciclovir Drugs 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 230000000840 anti-viral effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 230000002155 anti-virotic effect Effects 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- BLSQLHNBWJLIBQ-OZXSUGGESA-N (2R,4S)-terconazole Chemical compound C1CN(C(C)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2N=CN=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 BLSQLHNBWJLIBQ-OZXSUGGESA-N 0.000 description 1
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- BOXNENYOGRMVAM-UHFFFAOYSA-L [Na+].[Na+].[O-]P([O-])(Cl)=O Chemical compound [Na+].[Na+].[O-]P([O-])(Cl)=O BOXNENYOGRMVAM-UHFFFAOYSA-L 0.000 description 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- GHXRKGHKMRZBJH-UHFFFAOYSA-N boric acid Chemical compound OB(O)O.OB(O)O GHXRKGHKMRZBJH-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- SWXVUIWOUIDPGS-UHFFFAOYSA-N diacetone alcohol Natural products CC(=O)CC(C)(C)O SWXVUIWOUIDPGS-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229940089256 fungistat Drugs 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000013094 purity test Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000004457 water analysis Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A ganciclovir sodium hydrate, C9H12N5O4Na.2H2O, is prepared through dissolving ganciclovir in aqueous solution of sodium hydroxide, regulating pH value, stirring while adding unit adcohol or ketone with low-carbon chain, stirring, laying aside, sucking filtering, washing and vacuum drying the deposit to constant wt. at 40-80 deg.C. Its advantages include simple operation, low cost, relatively high purity, and high water solubility.
Description
Affiliated technical field
The present invention relates to ganciclovir sodium hydrate, preparation method and in medically application, the pharmaceutical preparation that this hydrate is made as bulk drug (as injection, eye drops and oral preparations etc.) is used for the treatment of the disease that causes because of some Causative virus.
Background technology
(Ganciclovir, former name are gancyclovir to ganciclovir, molecular formula C
9H
13N
5O
4) be a purine class antiviral commonly used of exploitation listing behind acyclovir.Its structure is similar to acyclovir, but its antivirus action is stronger than acyclovir, chemical property is also more stable, its chemistry 9-[[2-hydroxyl-1-(methylol) oxyethyl group by name] methyl] guanine, it is by people such as Verheyden (United States Patent (USP) 4355032,4423050) at first invention, at present domestic all have its bulk drug and preparation thereof to go on the market.
Because this solubleness less (about 4mg/ml) in water of ganciclovir, the preparation pharmaceutical preparation particularly aqueous solution 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 ganciclovir drug effect, how to improve its solubility property, avoid just seeming particularly important because of the toxic side effect of using solubility promoter to cause clinically.
The innovation and creation content
Shortcoming and defect in view of existing ganciclovir existence, the present invention will provide a kind of ganciclovir sodium hydrate, this ganciclovir sodium hydrate should have better solubility property under the prerequisite that guarantees the ganciclovir drug effect, thereby avoids the toxic side effect because of using solubility promoter to cause.
Another object of the present invention provides the preparation method of a sharp ganciclovir sodium hydrate of the present invention, characteristics such as that this method has is easy, with low cost, steady quality.
A further object of the invention be with ganciclovir sodium hydrate of the present invention as bulk drug, make injection, oral preparations, eye drops, for using clinically.
Concrete technical scheme is as follows:
A kind of name is called the compound of ganciclovir sodium hydrate, its chemistry 9-[[2-hydroxyl-1-(methylol) oxyethyl group by name] methyl] guanine sodium dihydrate, its molecular formula is C
9H
12N
5O
4Na2H
2O.This hydrate is a white crystalline powder, is difficult for the moisture absorption, and solvability is fine in water, and its solubleness is greater than 50%, and its antiviral activity and ganciclovir are suitable, and toxic reaction is lower.As the bulk drug of pharmaceutical preparation, be used to prepare injection, eye drops and oral preparations etc., to satisfy various needs clinically.
A kind of method for preparing the ganciclovir sodium hydrate:
Ganciclovir is dissolved in the sodium hydroxide solution, the pH value 10-14 of regulator solution, under agitation add and contain five carbon following unit alcohol or ketone, place, suction filtration, with above-mentioned organic solvent washing throw out, gained is deposited in 40-80 ℃ of drying under reduced pressure to constant weight, the white crystalline powder that obtains is the ganciclovir sodium hydrate.
According to technical scheme of the present invention, the described following unit alcohol of five carbon or the ketone of containing is wherein a kind of such as methyl alcohol, ethanol, propyl alcohol, butanols, acetone, also can be two kinds or five kinds mixture wherein.
This ganciclovir sodium hydrate has better solubility property, is a kind of ideal raw material medicine, can be used for preparing injection, eye drops and oral preparations etc., to satisfy various needs clinically.Pharmaceutically can be used for treating lower immune function concurrent cmv infection disease, cytomegaloviral retinitis, herpesvirus infection and hepatitis B etc.
The compound that medicine hydrate of the present invention contains the above-mentioned molecular formula for the treatment of significant quantity is an activeconstituents, and contains one or more pharmaceutically acceptable carriers.
The performance test of ganciclovir sodium hydrate: 1, in-vitro antibacterial test:
Adopt the described method of document [Acta Pharmaceutica Sinica 24 (5): 331,1989], extracorporeal antivirus effect activity by the ganciclovir sodium dihydrate of embodiment one method preparation is tested, compare simultaneously with commercial ganciclovir (tolerant within the dried frozen aquatic products), the result shows that strain suppresses the concentration (IC that 50% plaque forms to herpes simplex virus I-type (HSV-1) KOS in tissue culture for this product and commercial ganciclovir
50) be 0.125 μ g/ml.That is: ganciclovir is prepared into behind the ganciclovir sodium dihydrate the not influence of its antiviral activity.2. solubility test
Get ganciclovir sodium dihydrate 12.5g, put in the 25ml measuring bottle, thin up shakes up to scale, can obtain the solution of achromaticity and clarification, thus explanation: ganciclovir sodium of the present invention solvability in water is fine, and its solubleness is greater than 50%.And ganciclovir is almost insoluble in water.3. porosity test
Get the ganciclovir sodium dihydrate (method of embodiment one) for preparing by the present invention and get the about 1g of ganciclovir sodium (each 2 parts) for preparing by freeze-drying [United States Patent (USP) 4355032], behind the precision weighing, put simultaneously in 75% and 92.5% the moisture eliminator, regularly take out and claim to decide weight, and calculating moisture absorption ratio (moisture absorption ratio=[example weight before (example weight before test back example weight-test)/test] * 100%), the result shows: this law prepares the moisture absorption ratio of sample far below the sample by the freeze-drying preparation.The product that is this law preparation is difficult for the moisture absorption.4. purity test
With reference to high-efficient liquid phase chromatogram condition and the method under Chinese Pharmacopoeia relevant acyclovir (the 332nd page) inspection of version (two ones) in 2000 item, check by the sodium salt of different technology (crystallization and freeze-drying) preparation to the ganciclovir bulk drug and with this bulk drug simultaneously, the result shows, be starkly lower than the ganciclovir bulk drug and with the sodium salt of lyophilization preparation by the impurity in the ganciclovir sodium hydrate of this law preparation, that is: the purity by the product of this law preparation is higher.5. thermal weight loss and differential thermal analysis (are seen Fig. 1, Fig. 2)
Get by the sample (method of embodiment one) of the present invention's preparation and the sample of getting by freeze-drying [United States Patent (USP) 4355032] preparation and carry out thermal weight loss and differential thermal analysis simultaneously.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 ℃～120 ℃ weightlessness 11.2%, this with sample in to contain result's (theoretical value 11.5%) of the crystal water of 2 molecules 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; And a spot of weightlessness is all arranged before 100 ℃ by the sample of lyophilization preparation, be to contain a spot of free-water in the sample, 80 ℃～120 ℃ weightlessness 1.7%, differential thermal analysis result does not have endotherm(ic)peak between 100-120 ℃, no crystal water or recrystallisation solvent in the interpret sample.6. 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 105 ℃, and subtracting weight loss is 11.6%; Press Ka Shi aquametry mensuration moisture wherein in addition, the moisture determination result is 12.0%, two kind of unanimity as a result.This shows and only contains moisture in the sample, does not contain other solvent.Comprehensive thermal weight loss, differential thermal analysis and results of elemental analyses can prove the crystal water that contains 2 molecules in the sample
With existing ganciclovir sodium technology of preparing (United States Patent (USP) 4355032, with the freeze-drying preparation, do not contain crystal water) relatively, advantage of the present invention is that made final product is the ganciclovir sodium dihydrate, not only very easily dissolving in the aqueous solution, preparation technology is simple, low production cost, and also product purity is higher, steady quality, be difficult for the moisture absorption, preserve easily, clinical use is safer.
Description of drawings: Fig. 1. ganciclovir sodium hydrate differential thermal analysis curve Fig. 2. ganciclovir sodium hydrate thermogravimetic analysis (TGA) figure
Embodiment embodiment one: one of preparation method of ganciclovir sodium hydrate
Get ganciclovir 10g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 11, under agitation add ethanol 100ml, continue to stir after 10 minutes, placed 2 hours, suction filtration, add washing with alcohol 3 times (3 * 10ml), gained is deposited in 60 ℃ of drying under reduced pressure to constant weight, promptly get the 10.7g white crystalline powder.Results of elemental analyses: C34.41%; H5.14%; N22.29%; Na7.30%[ganciclovir sodium dihydrate (C
9H
12N
5O
4Na2H
2O) theoretical value: C34.48%; H5.11%; N22.35%; Na7.34%].Embodiment two: the preparation method's of ganciclovir sodium hydrate two
Get ganciclovir 10g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 10, under agitation add methyl alcohol 100ml, continue to stir after 10 minutes, placed 2 hours, suction filtration, add methanol wash 3 times (3 * 10ml), gained is deposited in 40 ℃ of drying under reduced pressure to constant weight, promptly get the 8.3g white crystalline powder.Results of elemental analyses: C34.03%; H5.25%; N22.22%; Na7.38%[ganciclovir sodium dihydrate (C
9H
12N
5O
4Na2H
2O) theoretical value: C34.48%; H5.11%; N22.35%; Na7.34%].Embodiment three: the preparation method's of ganciclovir sodium hydrate three
Get ganciclovir 10g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 12, under agitation add acetone 100ml, continue to stir after 10 minutes, placed 2 hours, suction filtration, add washing with acetone 3 times (3 * 10ml), gained is deposited in 70 ℃ of drying under reduced pressure to constant weight, promptly get the 9.7g white crystalline powder.Results of elemental analyses: C34.41%; H5.31%; N22.44%; Na7.50%[ganciclovir sodium dihydrate] (C
9H
12N
5O
4Na2H
2O) theoretical value: C34.48%; H5.11%; N22.35%; Na7.34%].Embodiment four: the preparation method's of ganciclovir sodium hydrate four
Get ganciclovir 10g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 14, under agitation add Virahol 100ml, continue to stir after 10 minutes, placed 2 hours, suction filtration, add washed with isopropyl alcohol 3 times (3 * 10ml), gained is deposited in 80 ℃ of drying under reduced pressure to constant weight, promptly get the 10.9g white crystalline powder.Results of elemental analyses: C34.35%; H5.11%; N22.21%; Na7.45%[ganciclovir sodium dihydrate (C
9H
12N
5O
4Na2H
2O) theoretical value: C34.48%; H5.11%; N22.35%; Na7.34%].Embodiment five: the preparation method's of ganciclovir sodium hydrate five
Get ganciclovir 10g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 11, under agitation add acetone and alcohol mixed solution (V: V=1: 1) 100ml, continue to stir after 10 minutes, placed 2 hours, 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 10.9g white crystalline powder.Results of elemental analyses: C34.39%; H5.15%; N22.24%; Na7.42%[ganciclovir sodium dihydrate (C
9H
12N
5O
4Na2H
2O) theoretical value: C34.48%; H5.11%; N22.35%; Na7.34%].Embodiment six: the preparation method's of ganciclovir sodium hydrate six
Get ganciclovir 10g, the dissolving of hydro-oxidation sodium solution, and the pH of regulator solution is 14, under agitation add acetone and isopropyl alcohol mixture (V: V=1: 1) 100ml, continue to stir after 10 minutes, placed 2 hours, suction filtration, add washed with isopropyl alcohol 3 times (3 * 10ml), gained is deposited in 80 ℃ of drying under reduced pressure to constant weight, promptly get the 10.9g white crystalline powder.Results of elemental analyses: C34.36%; H5.18%; N22.27%; Na7.46%[ganciclovir sodium dihydrate (C
9H
12N
5O
4Na2H
2O) theoretical value: C34.48%; H5.11%; N22.35%; Na7.34%].Embodiment seven: the preparation of ganciclovir sodium injection
Get ganciclovir sodium dihydrate 30g, after adding injection and being diluted with water to 500ml, divide 5ml can, promptly.Specification be the 300mg ganciclovir/.Be diluted to the concentration of 1mg/ml during use with suitable transfusion, for intravenous drip.Embodiment eight: the preparation of ganciclovir sodium freeze-dried preparation
Get ganciclovir sodium dihydrate 30g, after adding injection and being diluted with water to 250ml, divide the 2.5ml can in the 10ml cillin bottle, lyophilize promptly.Specification is 300mg ganciclovir/bottle.Be diluted to the concentration of 1mg/ml during use with suitable transfusion, for intravenous drip.Embodiment nine: the preparation of ganciclovir sodium transfusion
Get ganciclovir sodium dihydrate 3g, 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 50-500ml infusion bottle, for intravenous drip.Embodiment ten: the preparation of ganciclovir sodium eye drops
Get ganciclovir sodium dihydrate 3g, after adding 100ml 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 11: the preparation of ganciclovir sodium tablet
Get ganciclovir sodium dihydrate 30g, add an amount of auxiliary material (as starch, lactose or polyvinylpyrrolidone etc.) and make 100, specification is the 300mg/ sheet, for orally using.Embodiment 12: the capsular preparation of ganciclovir sodium
Get ganciclovir sodium dihydrate 30g, add an amount of auxiliary material (as starch, lactose or polyvinylpyrrolidone etc.) and mix, in 100 Capsuleses of packing into, specification is the 300mg/ grain, for orally using.
Claims (4)
1. the compound of a ganciclovir sodium hydrate, its chemistry 9-[[2-hydroxyl-1-(methylol) oxyethyl group by name] methyl] guanine sodium dihydrate, molecular formula is C
9H
12N
5O
4Na2H
2O.
2. the preparation method of a ganciclovir sodium hydrate, this method comprises the following steps: ganciclovir is dissolved in the sodium hydroxide solution, the pH value 10-14 of regulator solution, the unit alcohol or the ketone that under agitation add low carbon chain, place suction filtration, washing, gained is deposited in 40-80 ℃ of drying under reduced pressure to constant weight, is the ganciclovir sodium hydrate.
3. the preparation method of ganciclovir sodium hydrate according to claim 2, it is characterized in that the unit alcohol of described low carbon chain or ketone are wherein a kind of of methyl alcohol, ethanol, propyl alcohol, butanols, acetone, also can be the mixture below two kinds or six kinds wherein.
4. the ganciclovir sodium hydrate of claim 1 is as bulk drug, add pharmaceutically acceptable carrier, make injection, oral preparations, eye drops, be used for the treatment of lower immune function concurrent cmv infection disease, cytomegaloviral retinitis, herpesvirus infection and hepatitis B.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01133524 CN1125823C (en) | 2001-09-30 | 2001-09-30 | Ganciclovir sodium hydrate and its preparing process and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01133524 CN1125823C (en) | 2001-09-30 | 2001-09-30 | Ganciclovir sodium hydrate and its preparing process and application |
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| Publication Number | Publication Date |
|---|---|
| CN1342651A true CN1342651A (en) | 2002-04-03 |
| CN1125823C CN1125823C (en) | 2003-10-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 01133524 Expired - Fee Related CN1125823C (en) | 2001-09-30 | 2001-09-30 | Ganciclovir sodium hydrate and its preparing process and application |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004111049A1 (en) * | 2003-06-13 | 2004-12-23 | Lyogen Limited | Ganciclovir sodium salt in crystalline form |
| CN103524505A (en) * | 2013-10-30 | 2014-01-22 | 湖北华世通潜龙药业有限公司 | Crystal type ganciclovir sodium hydrate and preparing method thereof |
| CN103570716A (en) * | 2013-10-30 | 2014-02-12 | 湖北华世通潜龙药业有限公司 | Unhydrous crystal form of ganciclovir sodium and preparation method thereof |
| CN113476413A (en) * | 2021-08-09 | 2021-10-08 | 海南海灵化学制药有限公司 | Preparation method of ganciclovir sodium freeze-dried powder for injection |
| 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
- 2001-09-30 CN CN 01133524 patent/CN1125823C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004111049A1 (en) * | 2003-06-13 | 2004-12-23 | Lyogen Limited | Ganciclovir sodium salt in crystalline form |
| CN103524505A (en) * | 2013-10-30 | 2014-01-22 | 湖北华世通潜龙药业有限公司 | Crystal type ganciclovir sodium hydrate and preparing method thereof |
| CN103570716A (en) * | 2013-10-30 | 2014-02-12 | 湖北华世通潜龙药业有限公司 | Unhydrous crystal form of ganciclovir sodium and preparation method thereof |
| CN103570716B (en) * | 2013-10-30 | 2015-12-09 | 湖北华世通潜龙药业有限公司 | Anhydrous crystal forms of a kind of ganciclovir sodium and preparation method thereof |
| CN113476413A (en) * | 2021-08-09 | 2021-10-08 | 海南海灵化学制药有限公司 | Preparation method of ganciclovir sodium freeze-dried powder for injection |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1125823C (en) | 2003-10-29 |
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