CN1181829C - Jixitabin solution preparation - Google Patents
Jixitabin solution preparation Download PDFInfo
- Publication number
- CN1181829C CN1181829C CNB00133414XA CN00133414A CN1181829C CN 1181829 C CN1181829 C CN 1181829C CN B00133414X A CNB00133414X A CN B00133414XA CN 00133414 A CN00133414 A CN 00133414A CN 1181829 C CN1181829 C CN 1181829C
- Authority
- CN
- China
- Prior art keywords
- gemcitabine
- injection
- solvent
- water
- alkali
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000002360 preparation method Methods 0.000 title claims description 10
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims abstract description 48
- 229960005277 gemcitabine Drugs 0.000 claims abstract description 36
- 239000007924 injection Substances 0.000 claims abstract description 27
- 238000002347 injection Methods 0.000 claims abstract description 27
- 239000003513 alkali Substances 0.000 claims abstract description 26
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 37
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims 3
- 230000035479 physiological effects, processes and functions Effects 0.000 claims 1
- 239000003186 pharmaceutical solution Substances 0.000 abstract description 2
- 239000003978 infusion fluid Substances 0.000 description 22
- 229940090044 injection Drugs 0.000 description 17
- 229960005144 gemcitabine hydrochloride Drugs 0.000 description 11
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 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 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000008176 lyophilized powder Substances 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229940005876 gemcitabine injection Drugs 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002421 anti-septic effect Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
- 235000019800 disodium phosphate Nutrition 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- -1 nucleoside triphosphate Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 108010011356 Nucleoside phosphotransferase Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940027278 hetastarch Drugs 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 235000007715 potassium iodide Nutrition 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention discloses a pharmaceutical solution of Gemcitabine, which is composed of Gemcitabine alkali with medicine effective dose and pharmacologically acceptable solvent for injection.
Description
The present invention relates to a kind of pharmaceutical solutions of antitumor drug gemcitabine.
Gemcitabine (Gemcitabine), chemistry is by name 2 '-deoxidation-2 ', 2 '-difluoro cytidine, the β type; Molecular formula is C
9H
11F
2N
3O
4, molecular weight is 263.16, is a kind of effective antitumour medicine, the preparation of listing is the lyophilization injectable powder of its hydrochlorate at present.Gemcitabine hydrochloride is unstable in aqueous solution, and gemcitabine hydrochloride around placing under the 40 degree conditions, decomposes to 86% in the 0.1N hydrochloric acid solution according to research reports; Under the alkali condition of 0.1N sodium hydroxide, only remain 72% around under 40 degree conditions, placing.Therefore require gemcitabine hydrochloride lyophilized formulations dissolving back in 24 hours, must use clinically.Because it is acid that its hydrochlorate preparation is in aqueous solution, pH is about 2.0, so freeze dried powder must add the pH regulator agent and just can meet injection in the requirement more than 4.Even gemcitabine hydrochloride preparation pH value scope like this, in the market is still about 2.7～3.3.
In the medicine almost the injection more than 95% be the aqueous solution dosage form.Have only unsettled medicine just to adopt freeze dried powder, freeze dried powder and aqueous solution relatively have following shortcoming: 1. production cost height; 2. complex process, working condition requires high; 3. use inconvenience, need to inject solution and dissolve again, increased the chance of polluting.
We are by discovering in a large number, use the gemcitabine base and make raw material, with gemcitabine base water, ethanol, propylene glycol, glycerol, etc. dissolving alone or in combination, also can add PVP (polyvinylpyrrolidone), can obtain stable Jixitabin solution preparation, its stability and curative effect are identical with freeze dried powder.Gemcitabine hydrochloride is a prodrug, enter the interior back of body under neutrallty condition, gemcitabine separates with hydrochloric acid, gemcitabine (being base) is activated gemcitabine nucleoside diphosphate (dFdCDP) or nucleoside triphosphate (dFdCTP) by the nucleoside kinase metabolism in cell, is produced the cytotoxicity of gemcitabine by these two active component combineds effect.Therefore the curative effect of gemcitabine hydrochloride and gemcitabine base is identical.
Jixitabin solution preparation of the present invention is realized in the following manner:
Raw material: the gemcitabine base,
Production technology: gemcitabine alkali water, ethanol, propylene glycol, glycerol are dissolved as solvent separately or with their combinations, in case of necessity can be to wherein adding an amount of PVP or mannitol.
The buffer system that is suitable for injection of the present invention is that those keep any buffer system of the PH scope of aqueous solution preparation at 4.5-9, comprise material and combinations thereof such as phosphoric acid, citric acid, sodium dihydrogen phosphate, sodium hydrogen phosphate, acetate, Ascorbate, lactate, carbonate, Tris, preferably citric acid and sodium hydrogen phosphate buffer system.PH scope after these two kinds of composition combinations is consistent with human internal environment's pH value, can avoid the zest to human body as far as possible, can not cause uncomfortable reaction after the injection, and this system composition has complexation of metal ions and prevents autooxidation simultaneously.
Injection of the present invention can also add any be suitable for using in the injection stabilizing agent, isotonic agent, antiseptic, cosolvent etc.The stabilizing agent that can select is as hetastarch, polyvinylpyrrolidone, carboxymethyl cellulose, hydroxyethyl-cellulose, ethyl oleate, sorbitol, triglyceride, dextrin etc.Isotonic agent can be a sodium chloride, calcium chloride, potassium chloride, sodium iodide, potassium iodide etc.Antiseptic can be benzyl alcohol, phenethanol, quaternary ammonium salt, methaform, sorbic acid, methyl butex etc., cosolvent can be nonionic surfactant such as polyoxyethylene 20 sorbitan monooleate, glycerol, sorbitol, mannitol, propylene glycol, glucose, etc., other can be used and also can add the useful adjuvant of injection of the present invention.
Gemcitabine injection of the present invention and gemcitabine hydrochloride lyophilized powder injection compare the effect of KB cell killing:
Concentration (ng/ml) and clone's number (± SD)
50 25 12.5 6.25 1.25 0
Gemcitabine injection 18 ± 3 120 ± 5 209 ± 6 312 ± 12 410 ± 13 489 ± 16
Gemcitabine hydrochloride freeze-dried powder 16 ± 2 129 ± 3 211 ± 7 301 ± 9 423 ± 11 476 ± 12
Jixitabin solution preparation and gemcitabine hydrochloride lyophilized powder injection stability compare:
Time (moon) and medicament contg (%)
0 1 2 3
Gemcitabine injection 100.0 99.8 100.1 99.6
Gemcitabine hydrochloride lyophilized powder injection 100.0 100.8 99.2 99.7
Change gemcitabine hydrochloride lyophilized powder injection into solution, indicate in the research aspect this stability of drug and the dissolubility to have obtained breakthrough.
The present invention is described by the following examples, and these embodiment should be as the restriction to content of the present invention.
Embodiment 1: get gemcitabine alkali 200mg, with a little distilled water for injection dissolving, dose distilled water for injection again to 8ml, divide in the peace bottle of the 1ml that packs into, make the intravenous fluid that concentration is the 25mg/ml/ bottle.
Embodiment 2: get gemcitabine alkali 200mg, with a little distilled water for injection dissolving, dose distilled water for injection again to 16ml, divide in the peace bottle of the 1ml that packs into, make the intravenous fluid that concentration is the 12.5mg/ml/ bottle.
Embodiment 3: get gemcitabine alkali 200mg, with a little distilled water for injection dissolving, dose distilled water for injection again to 32ml, divide in the peace bottle of the 1ml that packs into, make the intravenous fluid that concentration is the 6.25mg/ml/ bottle.
Embodiment 4: gemcitabine alkali 200mg, make the intravenous fluid that concentration is 150mg/ml with the glycerol dissolving.
Embodiment 5: gemcitabine alkali 200mg, make the intravenous fluid that concentration is 75mg/ml with the glycerol dissolving.
Embodiment 6: gemcitabine alkali 200mg, make the intravenous fluid that concentration is 50mg/ml with the glycerol dissolving.
Embodiment 7: gemcitabine alkali 200mg, make the intravenous fluid that concentration is 100mg/ml with the propylene glycol dissolving.
Embodiment 8: gemcitabine alkali 200mg, make the intravenous fluid that concentration is 50mg/ml with the propylene glycol dissolving.
Embodiment 9: gemcitabine alkali 200mg, make the intravenous fluid that concentration is 40mg/ml with dissolve with ethanol.
Embodiment 10: gemcitabine alkali 200mg, make the intravenous fluid that concentration is 20mg/ml with dissolve with ethanol.
Embodiment 11: gemcitabine alkali 200mg, water: glycerol=dissolving in 99: 1 makes the intravenous fluid that concentration is the 25mg/ml/ bottle.
Embodiment 12: gemcitabine alkali 200mg, water: glycerol=dissolving in 1: 99 makes the intravenous fluid that concentration is the 25mg/ml/ bottle.
Embodiment 13: gemcitabine alkali 200mg, water: glycerol=dissolving in 50: 50 makes the intravenous fluid that concentration is the 25mg/ml/ bottle.
Embodiment 14: gemcitabine alkali 200mg, water: the intravenous fluid that concentration is the 25mg/ml/ bottle is made in propylene glycol=dissolving in 99: 1.
Embodiment 15: gemcitabine alkali 200mg, water: propylene glycol=dissolving in 1: 99 makes the intravenous fluid that concentration is the 25mg/ml/ bottle.
Embodiment 16: gemcitabine alkali 200mg, water: the intravenous fluid that concentration is the 25mg/ml/ bottle is made in propylene glycol=dissolving in 50: 50.
Embodiment 17: gemcitabine alkali 200mg, water: the intravenous fluid that concentration is the 25mg/ml/ bottle is made in ethanol=dissolving in 99: 1.
Embodiment 18: gemcitabine alkali 200mg, water: the intravenous fluid that concentration is the 25mg/ml/ bottle is made in ethanol=dissolving in 1: 99.
Embodiment 19: gemcitabine alkali 200mg, water: the intravenous fluid that concentration is the 25mg/ml/ bottle is made in ethanol=dissolving in 50: 50.
Embodiment 20: gemcitabine alkali 200mg, water: PVP=100: the intravenous fluid that concentration is the 25mg/ml/ bottle is made in 1 dissolving.
Embodiment 21: gemcitabine alkali 200mg, water: the intravenous fluid that concentration is the 25mg/ml/ bottle is made in mannitol=dissolving in 100: 1.
Embodiment 22: gemcitabine alkali 200mg, use phosphate buffered solution: mannitol: benzyl alcohol :=100: 1: 1: the intravenous fluid that concentration is the 25mg/ml/ bottle is made in dissolving.
Claims (8)
1. Jixitabin solution type injection, it consists of: the gemcitabine alkali of physiology effective dose, water, ethanol, propylene glycol, glycerol are made solvent and the available medicine acceptable auxiliary of preparation solution type injection agent separately or with their combinations.
2. the injection of claim 1, wherein solvent is a water.
3. the injection of claim 1, wherein solvent is an ethanol.
4. the injection of claim 1, wherein solvent is a propylene glycol.
5. the injection of claim 1, wherein solvent is a glycerol.
6. the injection of claim 1, wherein solvent is the mixed solvent of water and propylene glycol.
7. the injection of claim 1, wherein solvent is water and ethanol mixed solvent.
8. the injection of claim 1, wherein solvent is the mixed solvent of water and glycerol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB00133414XA CN1181829C (en) | 2000-11-03 | 2000-11-03 | Jixitabin solution preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB00133414XA CN1181829C (en) | 2000-11-03 | 2000-11-03 | Jixitabin solution preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1352944A CN1352944A (en) | 2002-06-12 |
| CN1181829C true CN1181829C (en) | 2004-12-29 |
Family
ID=4595704
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB00133414XA Expired - Fee Related CN1181829C (en) | 2000-11-03 | 2000-11-03 | Jixitabin solution preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1181829C (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10323278A1 (en) | 2003-05-21 | 2004-12-16 | Stada Arzneimittel Ag | Ready-to-use gemcitabine solution concentrates |
| DE10323279A1 (en) | 2003-05-21 | 2004-12-16 | Stada Arzneimittel Ag | Ready-to-use gemcitabine solutions |
| CN1302782C (en) * | 2005-01-17 | 2007-03-07 | 北京京卫燕康药物研究所有限公司 | Jixitabing hydrochloride solution type injection agent |
| CN102406603B (en) * | 2006-06-12 | 2015-12-16 | 齐鲁制药(海南)有限公司 | Supersaturated solution that gemcitabine hydrochloride is stable and preparation method thereof |
| EP2459170A2 (en) * | 2009-07-31 | 2012-06-06 | Astron Research Limited | A stable composition of ready-to-use gemcitabine injection |
| CN101606947B (en) * | 2009-08-06 | 2011-03-30 | 山东罗欣药业股份有限公司 | Gemcitabine hydrochloride composition and preparation method thereof |
| CN109077995A (en) * | 2012-04-27 | 2018-12-25 | 太阳医药工业有限公司 | I.e. pourable Jixitabin solution |
| CN102764241B (en) * | 2012-06-19 | 2013-07-03 | 哈药集团生物工程有限公司 | Freeze-dried pharmaceutical composition containing gemcitabine hydrochloride |
| CN103585168A (en) * | 2013-11-27 | 2014-02-19 | 哈尔滨誉衡药业股份有限公司 | Medicine composition containing gemcitabine hydrochloride |
| TWI674097B (en) * | 2014-06-25 | 2019-10-11 | 英商努卡那公眾有限公司 | Formulations of phosphate derivatives |
| CN108440625A (en) * | 2018-04-18 | 2018-08-24 | 日照市普达医药科技有限公司 | A kind of Difluoronucleosides class antimetabolite anticarcinogen destroying cellular replication |
-
2000
- 2000-11-03 CN CNB00133414XA patent/CN1181829C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1352944A (en) | 2002-06-12 |
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