CN100451023C - Levo-ornidazole phosphate, preparing process and use thereof - Google Patents
Levo-ornidazole phosphate, preparing process and use thereof Download PDFInfo
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- CN100451023C CN100451023C CNB2006101668932A CN200610166893A CN100451023C CN 100451023 C CN100451023 C CN 100451023C CN B2006101668932 A CNB2006101668932 A CN B2006101668932A CN 200610166893 A CN200610166893 A CN 200610166893A CN 100451023 C CN100451023 C CN 100451023C
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- ornidazole
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- phosphate
- pharmaceutical salts
- ornidazole phosphate
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- 229910019142 PO4 Inorganic materials 0.000 title claims abstract description 31
- 239000010452 phosphate Substances 0.000 title claims abstract description 31
- IPWKIXLWTCNBKN-ZCFIWIBFSA-N (2s)-1-chloro-3-(2-methyl-5-nitroimidazol-1-yl)propan-2-ol Chemical compound CC1=NC=C([N+]([O-])=O)N1C[C@H](O)CCl IPWKIXLWTCNBKN-ZCFIWIBFSA-N 0.000 title claims description 58
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 title claims description 30
- 238000000034 method Methods 0.000 title abstract description 6
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 2
- 159000000007 calcium salts Chemical class 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims description 2
- 159000000003 magnesium salts Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 239000002423 protozoacide Substances 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 2
- 230000003103 anti-anaerobic effect Effects 0.000 claims 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 claims 1
- -1 phosphate ester Chemical class 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 14
- 229910000397 disodium phosphate Inorganic materials 0.000 description 14
- 235000019800 disodium phosphate Nutrition 0.000 description 14
- 239000001488 sodium phosphate Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- IPWKIXLWTCNBKN-UHFFFAOYSA-N Madelen Chemical compound CC1=NC=C([N+]([O-])=O)N1CC(O)CCl IPWKIXLWTCNBKN-UHFFFAOYSA-N 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229960002313 ornidazole Drugs 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical group ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- VRFQGWDBONDCGH-UHFFFAOYSA-K P(=O)([O-])([O-])[O-].[Na+].[Na+].[Na+].[Cl+] Chemical compound P(=O)([O-])([O-])[O-].[Na+].[Na+].[Na+].[Cl+] VRFQGWDBONDCGH-UHFFFAOYSA-K 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
- WPGUUPJOAVPZBQ-UHFFFAOYSA-N [Cl].OP(O)(O)=O Chemical compound [Cl].OP(O)(O)=O WPGUUPJOAVPZBQ-UHFFFAOYSA-N 0.000 description 2
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229940058965 antiprotozoal agent against amoebiasis and other protozoal diseases nitroimidazole derivative Drugs 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012374 esterification agent Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 150000004957 nitroimidazoles Chemical class 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 229910052719 titanium Inorganic materials 0.000 description 2
- 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
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 208000010362 Protozoan Infections Diseases 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229920005549 butyl rubber Polymers 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000011122 softwood Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to L-aonitrate phosphate ester, its preparing process and use thereof.
Description
Technical field:
The present invention relates to levo-ornidazole phosphate and preparation method thereof and its purposes at field of medicaments.
Technical background:
Ornidazole is ((±) 1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitro imidazoles (Ornidazole, CAS 16773-42-5).Ornidazole is a nitro imidazole derivatives, is the medicine that a kind of powerful anaerobe resistant and protozoacide infect, and also is that newly the curative effect of development is higher behind metronidazole, the course of treatment is shorter, tolerance is better, the wider third generation nitro imidazole derivatives of distribution in the body.The anti-microbial effect of ornidazole is to be reduced into amino by the nitro in its molecule in oxygen-free environment, or interacts by the formation and the cellular constituent of free radical, thereby causes the death of microorganism.
Levo-ornidazole ((-) 1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitro imidazoles), Chinese patent (CN 200510068478.9, CN200510083517.2) has been described it and has been better than ornidazole and (r)-ornidazole aspect some drug side effects such as neurotoxicity.
Levo-ornidazole itself is water-soluble low especially, must be with recombiner to reach satisfied water soluble preparation.Yet people always expect to reduce the one-tenth mark of prescription so that reduce the issuable side reaction of patient.
Summary of the invention:
It is that main ingredient adds the preparation that suitable auxiliary material is made that purpose of the present invention provides the fabulous levo-ornidazole phosphate of a kind of water-soluble to reach with it at the problems referred to above.
The object of the present invention is to provide its structural formula of a kind of levo-ornidazole phosphate to be:
Another object of the present invention provides a kind of method for preparing levo-ornidazole phosphate.
A further object of the present invention provides the medical composition and its use of levo-ornidazole phosphate.
In more detail, the present invention includes hydrate, solvated compounds and the levo-ornidazole phosphate pharmaceutical salts of levo-ornidazole phosphate, the hydrate of levo-ornidazole phosphate pharmaceutical salts, solvated compounds.
Levo-ornidazole phosphate pharmaceutical salts of the present invention, its pharmaceutical salts are to comprise its sodium salt, sylvite, calcium salt, magnesium salts etc. at the alkaline earth salt that the phosphide position of its structure forms.
Levo-ornidazole phosphate of the present invention, levo-ornidazole phosphate pharmaceutical salts and Levo-ornidazole relatively have following advantage: this product solvability in water is fabulous to be more suitable for being developed as intravenous administration formulation; This product enters and can be hydrolyzed to Levo-ornidazole rapidly in the organism under the effect of phosphide enzyme and work, and it reaches maximum plasma concentration time ratio Levo-ornidazole early (being that onset is faster than Levo-ornidazole), and because that its close ester distributes in vivo is wider.
The preparation method of levo-ornidazole phosphate of the present invention is: be raw material with the Levo-ornidazole, with the solvent dissolving, with the phosphoric acid esterification agent reaction, be prepared into chlorine phosphoric acid intermediate.Then above-mentioned intermediate is hydrolyzed, promptly gets levo-ornidazole phosphate.
Action solvent is ethyl acetate, acetonitrile, tetrahydrofuran (THF), acetone, methylene dichloride, chloroform etc.
Phosphoric acid esterification agent is phosphorus oxychloride, tetrachloro tetra-sodium, temperature of reaction is-and 50-80 ℃, preferred 10-20 ℃.
The preparation method of preparation levo-ornidazole phosphate pharmaceutical salts is: with water, methyl alcohol, ethanol etc. is reaction solvent, with levo-ornidazole phosphate and yellow soda ash, sodium bicarbonate, sodium hydroxide, salt of wormwood, saleratus, potassium hydroxide reaction make (s)-ornidazole disodium phosphate, Levo-ornidazole Rhodiaphos DKP.
The preparation of Levo-ornidazole raw material can reference: a synthetic literary composition of ornidazole comes from Chinese Journal of Pharmaceuticals (2004/35/11), and different is to replace epoxy chloropropane with the dextrorotation epoxy chloropropane; Or make with reference to the preparation method of CN200510127033.3.
Pharmaceutical composition provided by the invention is that pharmaceutical salts with levo-ornidazole phosphate or levo-ornidazole phosphate is as activeconstituents and pharmaceutically acceptable carrier.
Form of administration can be pharmaceutically acceptable preparations such as tablet, capsule, dispersible tablet, oral liquid, infusion solutions, little pin, freeze-dried powder.
Pharmaceutical composition of the present invention can be used for preventing, improving and/or cures the disease that is caused by anaerobic infection or protozoan infection; Be particularly suitable for using medicine as people and animal doctor.
The pharmaceutical salts of levo-ornidazole phosphate of the present invention or levo-ornidazole phosphate is by the gross weight administration, and its amount is every kg body weight 1-100mg, and preferably the consumption of 24h is every kg body weight 1-20mg, also can adopt medication several times.
Preferred plan is that the amount that gives the pharmaceutical salts of levo-ornidazole phosphate or levo-ornidazole phosphate once a day is the 1-50mg/kg body weight, and preferred dose is the 3-20mg/kg body weight.In order to meet people or ideal occlusion regimen for animals, the difference of the visual state of an illness weight of this dosage, treatment difficulty or ease fluctuates up and down, or follows the doctor's advice.
Below in conjunction with embodiment the present invention is described in further detail, but should understands the non-scope that only limits to these embodiment of scope of the present invention.
Embodiment 1: the preparation of levo-ornidazole phosphate
Levo-ornidazole 110g is dissolved in the exsiccant ethyl acetate 500ml solution, drip phosphorus oxychloride 100ml, control reaction temperature is at 10-20 ℃, liquid phase control reaction is to the peak that does not have Levo-ornidazole substantially, the reclaim under reduced pressure ethyl acetate gets chlorine phosphoric acid intermediate, and cooling down, slowly add pure water 600ml, hydrolysis reaction 1 hour, slowly adding 10% sodium carbonate solution adjust pH is 6.0, is evaporated to dried, add methyl alcohol 500ml, filter, add 500ml sherwood oil, freezing crystallization in the filtrate, filter, get levo-ornidazole phosphate 121g.
[purity: 99.3%, chromatographic condition: moving phase is the potassium dihydrogen phosphate (transferring pH with triethylamine is 6.0)=35: 65 of methyl alcohol: 0.05mol/L; Chromatographic column: Kromasil C18 5u, 250 * 4.6mm; ]
Embodiment 2: the preparation of (s)-ornidazole disodium phosphate
The 100g levo-ornidazole phosphate with 90% dissolve with methanol, is slowly added yellow soda ash and produces to there being bubble, add the 1000ml dehydrated alcohol again, freezing crystallization filters, and obtains white (s)-ornidazole disodium phosphate solid 89g.[specific optical rotation :-19.8 ° of C=1, water is made solvent; Purity: 99.6%, chromatographic condition: moving phase is the potassium dihydrogen phosphate (transferring pH with triethylamine is 6.0)=35: 65 of methyl alcohol: 0.05mol/L; Chromatographic column: Kromasil C18 5u, 250 * 4.6mm; ]
Embodiment 3: the preparation of (s)-ornidazole disodium phosphate sheet.
Prescription:
(s)-ornidazole disodium phosphate 390g
Starch 100g
Microcrystalline Cellulose 85g
Magnesium stearate 2.0g
Make 1000
Method for making: take by weighing (s)-ornidazole disodium phosphate, the Microcrystalline Cellulose of 100g starch and recipe quantity, mixing was pulverized 80 mesh sieves., granulate with 20 mesh sieves, material system softwood with 4% Vltra tears (E-30) solution in 50-60 ℃ of moisture content about 3% that is dried in the particle.Cross the whole grain of 20 mesh sieves, add magnesium stearate, mix eventually, survey intermediate content, stator is heavy; Compressing tablet.
Embodiment 4:: the preparation of (s)-ornidazole disodium phosphate sodium-chlor transfusion
Prescription:
(s)-ornidazole disodium phosphate 39.5g
Sodium-chlor 89g
Water for injection 10L
Make 10000ml
Method for making: the (s)-ornidazole disodium phosphate and the sodium-chlor that take by weighing recipe quantity, add injection water 10L, stir, molten clear, transferring pH with citric acid is 3.5, adds 0.1% gac in above-mentioned solution, stir, placed 15 minutes, 5 microns titanium rods take off charcoal, again through the smart filter of the millipore filtration of 0.45 micron of filter cartridge and 0.22 micron; Embedding is in the 100ml glass infusion bottle, and 105 ℃ of flowing steams were sterilized 45 minutes, promptly gets the transfusion of (s)-ornidazole disodium phosphate sodium-chlor.
Embodiment 5: the preparation of (s)-ornidazole disodium phosphate injection liquid
Prescription:
(s)-ornidazole disodium phosphate 39.5g
Water for injection 1000ml
Make 1000ml
Method for making: take by weighing the (s)-ornidazole disodium phosphate of recipe quantity, add injection water 1000ml, stir, molten clear, transferring pH with citric acid is 3.5; Add 0.1% gac in above-mentioned solution, stir, placed 15 minutes, 5 microns titanium rods take off charcoal, filter through the millipore filtration essence of 0.45 micron of filter cartridge and 0.22 micron again; Embedding is in the 10ml ampoule, and 100 ℃ of flowing steams were sterilized 45 minutes, promptly got its injection liquid.
Embodiment 6: the preparation of injection (s)-ornidazole disodium phosphate
Prescription: (s)-ornidazole disodium phosphate 39.5g
Water for injection 100ml
Make 100 bottles
The (s)-ornidazole disodium phosphate that takes by weighing recipe quantity dissolves with water for injection, after add needle-use activated carbon absorption 30 minutes after carbon removal, Sterile Filtration (0.22 μ m), after testing, be sub-packed in after filtrate is up to specification in the control microbiotic cillin bottle, place in the vacuum freezing drying oven and carried out lyophilize 48 hours, add a cover butyl rubber plug, and roll the envelope aluminium lid promptly get its freeze-dried preparation.
Claims (4)
1. levo-ornidazole phosphate or its pharmaceutical salts, the chemical structural formula of described levo-ornidazole phosphate is as follows:
2. according to the described levo-ornidazole phosphate of claim 1 or its pharmaceutical salts, wherein said pharmaceutical salts is sodium salt, sylvite, calcium salt, the magnesium salts that forms at the phosphide group position of its chemical structure.
3. a medicinal compositions is characterized in that, contain the treatment effective dose according to claim 1 levo-ornidazole phosphate or its pharmaceutical salts as activeconstituents and pharmaceutically acceptable carrier.
4. according to the purposes of the described pharmaceutical composition of claim 3, be used for the medicine that production for treating anti anaerobic bacteria infection and protozoacide infect.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101668932A CN100451023C (en) | 2006-01-06 | 2006-12-15 | Levo-ornidazole phosphate, preparing process and use thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610041611.6 | 2006-01-06 | ||
| CN 200610041611 CN1803811A (en) | 2006-01-06 | 2006-01-06 | Nitro imidazole derivative, its preparation method and uses |
| CNB2006101668932A CN100451023C (en) | 2006-01-06 | 2006-12-15 | Levo-ornidazole phosphate, preparing process and use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101007823A CN101007823A (en) | 2007-08-01 |
| CN100451023C true CN100451023C (en) | 2009-01-14 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB2006101668932A Active CN100451023C (en) | 2006-01-06 | 2006-12-15 | Levo-ornidazole phosphate, preparing process and use thereof |
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| CN (1) | CN100451023C (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101177433B (en) * | 2007-12-05 | 2010-10-06 | 陕西新安医药科技有限公司 | (s)-ornidazole disodium phosphate pentahydrate as well as preparation method and uses thereof |
| CN102731571A (en) * | 2012-02-14 | 2012-10-17 | 陕西合成药业有限公司 | Novel crystalline s-(-)-ornidazole phosphate disodium hydrate and application thereof |
| CN104610356A (en) * | 2014-11-04 | 2015-05-13 | 扬子江药业集团南京海陵药业有限公司 | Stable phosphate crystal and preparation method thereof |
| CN104447870B (en) * | 2014-11-05 | 2017-07-25 | 扬子江药业集团南京海陵药业有限公司 | The synthetic method of the sodium impurity of levo-ornidazole phosphate two |
| CN104311597A (en) * | 2014-11-05 | 2015-01-28 | 扬子江药业集团南京海陵药业有限公司 | Industrial production method of s-(-)-ornidazole disodium phosphate |
| CN106467558A (en) * | 2015-08-18 | 2017-03-01 | 陕西合成药业股份有限公司 | A kind of phosphoric acid l-ornidazole ester two sodium crystal and preparation method thereof and the purposes of Pharmaceutical composition |
| CN106667924A (en) * | 2015-11-05 | 2017-05-17 | 陕西合成药业股份有限公司 | Stable S-(-)-ornidazol disodium phosphate freeze-dried preparation and preparation method thereof |
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| CN108409786A (en) * | 2018-02-10 | 2018-08-17 | 扬子江药业集团南京海陵药业有限公司 | A kind of industrialized preparing process of phosphoric acid l-ornidazole ester disodium hydrate |
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| CN1400312A (en) * | 2002-08-23 | 2003-03-05 | 中国科学院上海有机化学研究所 | Enzyme method resolution method of racemic ornidazole |
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