CN101108169A - Penciclovir freeze dried and method of manufacturing the same - Google Patents
Penciclovir freeze dried and method of manufacturing the same Download PDFInfo
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- CN101108169A CN101108169A CNA2007100700189A CN200710070018A CN101108169A CN 101108169 A CN101108169 A CN 101108169A CN A2007100700189 A CNA2007100700189 A CN A2007100700189A CN 200710070018 A CN200710070018 A CN 200710070018A CN 101108169 A CN101108169 A CN 101108169A
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- penciclovir
- excipient
- injectable powder
- lyophilized injectable
- powder according
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- 229960001179 penciclovir Drugs 0.000 title claims abstract description 62
- JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 238000004519 manufacturing process Methods 0.000 title 1
- 239000000843 powder Substances 0.000 claims abstract description 30
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 23
- 238000002347 injection Methods 0.000 claims abstract description 14
- 239000007924 injection Substances 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 229920002307 Dextran Polymers 0.000 claims abstract description 5
- BRPTUOYNOCSFRJ-FYZOBXCZSA-N sodium (2S)-4-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)butan-1-olate Chemical class [Na+].Nc1nc(=O)c2ncn(CC[C@H](CO)C[O-])c2[nH]1 BRPTUOYNOCSFRJ-FYZOBXCZSA-N 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 29
- 238000005352 clarification Methods 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 238000004108 freeze drying Methods 0.000 claims description 12
- 238000012856 packing Methods 0.000 claims description 11
- 239000008215 water for injection Substances 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- 238000000859 sublimation Methods 0.000 claims description 7
- 230000008022 sublimation Effects 0.000 claims description 7
- 238000010792 warming Methods 0.000 claims description 7
- 238000004821 distillation Methods 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims 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 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 238000011068 loading method Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 4
- 230000008014 freezing Effects 0.000 abstract description 2
- 238000007710 freezing Methods 0.000 abstract description 2
- 229940109850 royal jelly Drugs 0.000 abstract 2
- 230000002950 deficient Effects 0.000 abstract 1
- 238000005286 illumination Methods 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 230000005496 eutectics Effects 0.000 description 5
- 229930182470 glycoside Natural products 0.000 description 5
- 150000002338 glycosides Chemical class 0.000 description 5
- 239000002932 luster Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 229960004396 famciclovir Drugs 0.000 description 4
- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 description 4
- 241000700584 Simplexvirus Species 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- KGSIOVLUJYQLKR-UHFFFAOYSA-N [[4-(2-amino-6-oxo-3h-purin-9-yl)-2-(hydroxymethyl)butoxy]-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C=N2 KGSIOVLUJYQLKR-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- -1 penciclovir monophosphate Chemical class 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- YKBGVTZYEHREMT-UHFFFAOYSA-N 2-amino-9-[4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(CO)O1 YKBGVTZYEHREMT-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 208000001688 Herpes Genitalis Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 208000029433 Herpesviridae infectious disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000021472 generally recognized as safe Nutrition 0.000 description 1
- 201000004946 genital herpes Diseases 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 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 1
- 238000013112 stability test Methods 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Images
Abstract
The invention relates to the technical field of medical technology, in particular to a penciclovir lyophilized royal jelly powder injection and its preparation method, which comprises penciclovir and excipient. The powder injection is made by making penciclovir into penciclovir sodium salt, add the excipient and then freeze out. The weight ratio of the penciclovir and the excipient is: 1:0.2 to 3; the excipient comprises low molecular dextran. The invention resolves the problem of defective water-solubility in the prior art. Besides, with the freezing out technology and by adding low molecular dextran as the excipient, the invention enhances the solubility and stability of penciclovir, resolves the problem of low biologic utilization rate of penciclovir and ensures the safety and convenience of medication. What is more, the invention also provides the preparation method for the penciclovir lyophilized royal jelly powder injection.
Description
Technical field
The present invention relates to medical technical field, be specifically related to a kind of penciclovir lyophilized injectable powder and preparation method thereof.
Background technology
Penciclovir (molecular formula: C
10H
15N
5O
3) be a kind of ucleosides antiviral agents.External have inhibitory action to I type and II herpes simplex virus type, in virus infected cell, virus thymidine kinases (Thymidine kinase, TK) this product phosphoric acid is turned to the penciclovir monophosphate, cell kinase is converted into the penciclovir triphosphate with the penciclovir monophosphate then.Experiment in vitro shows, penciclovir triphosphate and NSC 22837 triphosphate competitive inhibition herpes simplex virus polymerase, thus selectivity inhibition herpes simplex virus dna synthesizes and duplicates.
The precursor medicine (prodrug) of penciclovir (PCV) is famciclovir (FCV), and it is converted into the PCV of antiviral activity in vivo through the enzyme effect.Its equal at home and abroad approved is used for the treatment of the infection (as genital herpes, herpes zoster etc.) of various herpesviruss at present, and is treating the clinical experiment of chronic viral hepatitis B.The oral administration biaavailability of FCV is about 77%, and than the strong 3-4 of PCV doubly, so FCV is developed to oral tablet, and PCV has only cream at present.Because the complication (as tumor, leukemia, the concurrent herpesvirus infection of AIDS VICTIMS etc.) to patient with severe symptoms and immunologic hypofunction patient just needs the penciclovir injection.The existing open report that the penciclovir lyophilized injectable powder is not also arranged.
Summary of the invention
In order to solve above-mentioned technical problem, one object of the present invention is to provide the penciclovir lyophilized injectable powder of a kind of good water solubility, bioavailability height, good stability.
Another object of the present invention is the preparation method that is to provide a kind of above-mentioned penciclovir lyophilized injectable powder.
In order to realize first above-mentioned purpose, the present invention has adopted following technical scheme:
A kind of penciclovir lyophilized injectable powder, comprise penciclovir and excipient, this injectable powder is by earlier penciclovir being made the penciclovir sodium salt, adding the excipient lyophilizing then makes, the weight ratio of described penciclovir and excipient is 1.0: 0.2～3.0, and described excipient comprises low molecular dextran.
As preferably, described excipient also comprises one or more mixing in mannitol, lactose, the sodium chloride.
As preferably, the weight ratio of penciclovir and excipient is 1.0: 0.4～3.0.As most preferably, the weight ratio of penciclovir and excipient is 1: 0.4.
As preferably, the specification of described injectable powder is every bottle and contains penciclovir 125mg, 250mg, 500mg or 750mg.
In order to realize second above-mentioned purpose, the invention provides the preparation method of above-mentioned penciclovir lyophilized injectable powder, comprise the steps:
(1) penciclovir is dissolved to clarification with sodium hydroxide solution, makes solution A;
(2) excipient is mixed with solution earlier with water for injection, adds active carbon then, boil, cold filtration is made solution B then;
(3) mix above-mentioned solution A and solution B, add active carbon, stir, filter, add the injection water to prescribed volume, packing;
(4) the packing goods are put into carried out lyophilization in the freezer dryer;
(5) tamponade outlet under the vacuum.
As preferably, pre-freeze 2～8 hours behind the inlet in the above-mentioned step (4), shelf temperature is to-60 ℃～-40 ℃, and products temperature be-30 ℃～-20 ℃, opens the vacuum pump goods and begins to distil, and the sublimation stage products temperature is controlled at-25 ℃～-15 ℃.
As preferably, treat that waterline on earth in the above-mentioned step (5) after, products temperature slowly is warming up to 35～39 ℃, shelf temperature is 39～42 ℃, is incubated 6～16 hours, then tamponade outlet under the vacuum.
As preferably, the pH value of described solution A is 10.5～11.5.
As preferably, the volume of the packing loading amount of described step (3) is 4～5ml.
Penciclovir lyophilized injectable powder of the present invention, solved the problem of poorly water-soluble in the prior art, adopt freeze drying technology, and add low molecular dextran as excipient, the dissolubility and the stability of penciclovir have been improved, solve the problem of the bioavailability difference of penciclovir, guaranteed the safety and the convenience of medication.As excipient, finished product can't molding for independent employing mannitol.
When using clinically, add an amount of aseptic medicinal aqueous diluent (for example: G/W, normal saline, water for injection and other known aqueous diluent), be diluted to for intravenous drip or intramuscular injection injection.Clinical effectiveness shows, this product has efficiently, the low toxicity characteristics, viral infection there is remarkable inhibitory action, complication for patient with severe symptoms and immunologic hypofunction patient can give the quick control state of an illness, compare with the same veriety injection acyclovir that has gone on the market at present, good effect, consumption is little, the medication number of times reduces, and patient's compliance is good.
Simultaneously, the present invention has also adopted special freeze drying process, has solved owing to the little technological deficiency of penciclovir dissolubility in water, and freezing curve is easy to grasp, the finished product forming, and no atrophy, neat and artistic.Simultaneously and since this product have stronger draw moist, so adopted long insulation, with the assurance moisture Control in standard.
Description of drawings
Fig. 1 is the freeze-drying curve figure of the embodiment of the invention 1.Wherein dotted line is represented shelf temperature, and solid line is represented products temperature.
The specific embodiment
Below by specific embodiment the present invention is further specified.
Embodiment 1:
Get penciclovir 250g, be dissolved to clarification (control pH value 11.0) with 5% sodium hydroxide solution; Low molecule dextrorotation pool glycosides 100g is mixed with 10% solution earlier with water for injection, adds 0.5% active carbon, boils and boils 30min, cold filtration.Above-mentioned two kinds of solution are mixed, add 0.5% active carbon again, stir 30min, filter, content is surveyed in sampling, adds the injection water to prescribed volume, surveys pH value.The packing goods are put into and are carried out lyophilization (freeze-drying curve as shown in Figure 1) in the freezer dryer, pre-freeze is 3 hours behind the inlet, shelf temperature is to-40 ℃, and products temperature is-25 ℃, opens the vacuum pump goods and begins distillation, the sublimation stage products temperature is controlled at-18 ℃ (the goods eutectic point is about-9 ℃), after treating that waterline on earth, products temperature slowly is warming up to about 37 ℃, and shelf temperature is 42 ℃, be incubated 8 hours, tamponade outlet under the vacuum.
Embodiment 2:
Get penciclovir 300g, be dissolved to clarification (control pH value 11.0) with 5% sodium hydroxide solution; Low molecule dextrorotation pool glycosides 120g is mixed with 10% solution earlier with water for injection, adds 0.5% active carbon, boils and boils 30min, cold filtration.Above-mentioned two kinds of solution are mixed, add 0.5% active carbon again, stir 30min, filter, content is surveyed in sampling, adds the injection water to prescribed volume, surveys pH value.The packing goods are put into and are carried out lyophilization in the freezer dryer, pre-freeze is 4 hours behind the inlet, shelf temperature is to-45 ℃, and products temperature is-25 ℃, opens the vacuum pump goods and begins distillation, the sublimation stage products temperature is controlled at-20 ℃ (the goods eutectic point is about-9 ℃), after treating that waterline on earth, products temperature slowly is warming up to about 37 ℃, and shelf temperature is 40 ℃, be incubated 10 hours, tamponade outlet under the vacuum.
Embodiment 3:
Get penciclovir 400g, be dissolved to clarification (control pH value 11.0) with 5% sodium hydroxide solution; Low molecule dextrorotation pool glycosides 160g is mixed with 10% solution earlier with water for injection, adds 0.5% active carbon, boils and boils 30min, cold filtration.Above-mentioned two kinds of solution are mixed, add 0.5% active carbon again, stir 30min, filter, content is surveyed in sampling, adds the injection water to prescribed volume, surveys pH value.The packing goods are put into and are carried out lyophilization in the freezer dryer, pre-freeze is 5 hours behind the inlet, shelf temperature is to-50 ℃, and products temperature is-30 ℃, opens the vacuum pump goods and begins distillation, the sublimation stage products temperature is controlled at-20 ℃ (the goods eutectic point is about-9 ℃), after treating that waterline on earth, products temperature slowly is warming up to about 37 ℃, and shelf temperature is 41 ℃, be incubated 12 hours, tamponade outlet under the vacuum.
Embodiment 4:
Get penciclovir 500g, be dissolved to clarification (control pH value 10.5) with 5% sodium hydroxide solution; Low molecule dextrorotation pool glycosides 200g is mixed with 10% solution earlier with water for injection, adds 0.5% active carbon, boils and boils 30min, cold filtration.Above-mentioned two kinds of solution are mixed, add 0.5% active carbon again, stir 30min, filter, content is surveyed in sampling, adds the injection water to prescribed volume, surveys pH value.The packing goods are put into and are carried out lyophilization in the freezer dryer, pre-freeze is 6 hours behind the inlet, shelf temperature is to-50 ℃, and products temperature is-30 ℃, opens the vacuum pump goods and begins distillation, the sublimation stage products temperature is controlled at-25 ℃ (the goods eutectic point is about-9 ℃), after treating that waterline on earth, products temperature slowly is warming up to about 37 ℃, and shelf temperature is 40 ℃, be incubated 12 hours, tamponade outlet under the vacuum.
Embodiment 5:
Get penciclovir 250g, be dissolved to clarification (control pH value 11.5) with 5% sodium hydroxide solution; Low molecule dextrorotation pool glycosides 400g is mixed with 10% solution earlier with water for injection, adds 0.5% active carbon, boils and boils 30min, cold filtration.Above-mentioned two kinds of solution are mixed, add 0.5% active carbon again, stir 30min, filter, content is surveyed in sampling, adds the injection water to prescribed volume, surveys pH value.The packing goods are put into and are carried out lyophilization (freeze-drying curve as shown in Figure 1) in the freezer dryer, pre-freeze is 3 hours behind the inlet, shelf temperature is to-40 ℃, and products temperature is-25 ℃, opens the vacuum pump goods and begins distillation, the sublimation stage products temperature is controlled at-18 ℃ (the goods eutectic point is about-9 ℃), after treating that waterline on earth, products temperature slowly is warming up to about 37 ℃, and shelf temperature is 42 ℃, be incubated 8 hours, tamponade outlet under the vacuum.
Experimental example 1:
The stability test of penciclovir lyophilized injectable powder.
The penciclovir lyophilized injectable powder that the foregoing description is made carries out preliminarily stabilised investigation (4000LX illumination placement 10 days down, high temperature were placed 10 days down for 60 ℃), and in the tenth day sampling and measuring, the result was shown in table 1～table 5.
Table 1: embodiment 1 study on the stability result
| Natural law | Appearance luster | Clarity | PH value | Content (labelled amount %) | Related substance (%) |
| 0 | The white block | Achromaticity and clarification | 10.91 | 103.3 | 0.27 |
| 4000LX illumination in 10 days | The white block | Achromaticity and clarification | 10.85 | 103.7 | 0.36 |
| High temperature was 60 ℃ in 10 days | The white block | Achromaticity and clarification | 10.87 | 103.1 | 0.47 |
Table 2: embodiment 2 study on the stability results
| Natural law | Appearance luster | Clarity | PH value | Content (labelled amount %) | Related substance (%) |
| 0 | The white block | Achromaticity and clarification | 10.95 | 102.8 | 030 |
| 4000LX illumination in 10 days | The white block | Achromaticity and clarification | 10.80 | 103.1 | 0.37 |
| High temperature was 60 ℃ in 10 days | The white block | Achromaticity and clarification | 10.85 | 102.6 | 0.46 |
Table 3: embodiment 3 study on the stability results
| Natural law | Appearance luster | Clarity | PH value | Content (labelled amount %) | Related substance (%) |
| 0 | The white block | Achromaticity and clarification | 10.84 | 101.6 | 020 |
| 4000LX illumination in 10 days | The white block | Achromaticity and clarification | 10.87 | 101.1 | 0.28 |
| High temperature was 60 ℃ in 10 days | The white block | Achromaticity and clarification | 10.90 | 102.3 | 0.38 |
Table 4: embodiment 4 study on the stability results
| Natural law | Appearance luster | Clarity | PH value | Content (labelled amount %) | Related substance (%) |
| 0 | The white block | Achromaticity and clarification | 10.80 | 102.5 | 0.31 |
| 4000LX illumination in 10 days | The white block | Achromaticity and clarification | 10.84 | 102.1 | 0.39 |
| High temperature was 60 ℃ in 10 days | The white block | Achromaticity and clarification | 10.85 | 102.8 | 0.45 |
Table 5: embodiment 5 study on the stability results
| Natural law | Appearance luster | Clarity | PH value | Content (labelled amount %) | Related substance (%) |
| 0 | The white block | Achromaticity and clarification | 10.91 | 103.3 | 0.27 |
| 4000LX illumination in 10 days | The white block | Achromaticity and clarification | 10.85 | 103.7 | 0.36 |
| High temperature was 60 ℃ in 10 days | The white block | Achromaticity and clarification | 10.87 | 103.1 | 0.47 |
Above result shows: penciclovir lyophilized injectable powder of the present invention can be rebuild the injection that obtains clear rapidly after adding water, and this fine solubility and stability have guaranteed the safety and the convenience of medication.
Experimental example 2:
The Generally Recognized as safe of penciclovir lyophilized injectable powder
The penciclovir lyophilized injectable powder that the foregoing description 1～5 makes is done general safety experiment, and experimental result is non-stimulated, the irritated reaction of nothing, does not also have haemolysis.
Claims (10)
1. penciclovir lyophilized injectable powder, comprise penciclovir and excipient, it is characterized in that this injectable powder is by earlier penciclovir being made the penciclovir sodium salt, adding the excipient lyophilizing then makes, the weight ratio of described penciclovir and excipient is 1.0: 0.2～3.0, and described excipient comprises low molecular dextran.
2. a kind of penciclovir lyophilized injectable powder according to claim 1 is characterized in that described excipient also comprises one or more mixing in mannitol, lactose, the sodium chloride.
3. a kind of penciclovir lyophilized injectable powder according to claim 1 and 2, the weight ratio that it is characterized in that penciclovir and excipient is 1: 0.4～3.
4. a kind of penciclovir lyophilized injectable powder according to claim 3, the weight ratio that it is characterized in that penciclovir and excipient is 1: 0.4.
5. a kind of penciclovir lyophilized injectable powder according to claim 1 and 2, the specification that it is characterized in that described injectable powder are every bottle and contain penciclovir 125mg, 250mg, 500mg or 750mg.
6. the preparation method of a kind of penciclovir lyophilized injectable powder according to claim 1 is characterized in that comprising the steps:
(1) penciclovir is dissolved to clarification with sodium hydroxide solution, makes solution A;
(2) excipient is mixed with solution earlier with water for injection, adds active carbon then, boil, cold filtration is made solution B then;
(3) mix above-mentioned solution A and solution B, add active carbon, stir, filter, add the injection water to prescribed volume, packing;
(4) the packing goods are put into carried out lyophilization in the freezer dryer;
(5) tamponade outlet under the vacuum.
7. the preparation method of a kind of penciclovir lyophilized injectable powder according to claim 6, it is characterized in that behind step (4) inlet pre-freeze 2～8 hours, shelf temperature is to-60 ℃～-40 ℃, products temperature is-30 ℃～-20 ℃, open the vacuum pump goods and begin distillation, the sublimation stage products temperature is controlled at-25 ℃～-15 ℃.
8. the preparation method of a kind of penciclovir lyophilized injectable powder according to claim 6, after it is characterized in that step (5) treats that waterline on earth, products temperature slowly is warming up to 35～39 ℃, and shelf temperature is 39～42 ℃, be incubated 6～16 hours, then tamponade outlet under the vacuum.
9. the preparation method of a kind of penciclovir lyophilized injectable powder according to claim 6, the pH value that it is characterized in that solution A is 10.5～11.5.
10. the preparation method of a kind of penciclovir lyophilized injectable powder according to claim 6, the volume that it is characterized in that the packing loading amount of step (3) is 1～10ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710070018A CN100594889C (en) | 2007-07-13 | 2007-07-13 | Penciclovir freeze dried and method of manufacturing the same |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710070018A CN100594889C (en) | 2007-07-13 | 2007-07-13 | Penciclovir freeze dried and method of manufacturing the same |
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| Publication Number | Publication Date |
|---|---|
| CN101108169A true CN101108169A (en) | 2008-01-23 |
| CN100594889C CN100594889C (en) | 2010-03-24 |
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|---|---|---|---|
| CN200710070018A Active CN100594889C (en) | 2007-07-13 | 2007-07-13 | Penciclovir freeze dried and method of manufacturing the same |
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| CN (1) | CN100594889C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102210686A (en) * | 2011-04-07 | 2011-10-12 | 罗诚 | Pharmaceutical composition containing ganciclovir compound, and preparation method thereof |
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2007
- 2007-07-13 CN CN200710070018A patent/CN100594889C/en active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102210686A (en) * | 2011-04-07 | 2011-10-12 | 罗诚 | Pharmaceutical composition containing ganciclovir compound, and preparation method thereof |
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| Publication number | Publication date |
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| CN100594889C (en) | 2010-03-24 |
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