CN102114020B - A kind of Pharmaceutical composition containing besifloxacin or its salt and preparation method thereof - Google Patents
A kind of Pharmaceutical composition containing besifloxacin or its salt and preparation method thereof Download PDFInfo
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- CN102114020B CN102114020B CN200910244381.7A CN200910244381A CN102114020B CN 102114020 B CN102114020 B CN 102114020B CN 200910244381 A CN200910244381 A CN 200910244381A CN 102114020 B CN102114020 B CN 102114020B
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- CN
- China
- Prior art keywords
- besifloxacin hydrochloride
- solution
- sodium
- besifloxacin
- hydrochloride
- Prior art date
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Links
- 229960004024 besifloxacin Drugs 0.000 title claims abstract description 42
- QFFGVLORLPOAEC-SNVBAGLBSA-N besifloxacin Chemical compound C1[C@H](N)CCCCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1Cl QFFGVLORLPOAEC-SNVBAGLBSA-N 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 150000003839 salts Chemical class 0.000 title abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 26
- 239000000243 solution Substances 0.000 claims description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 229920002472 Starch Polymers 0.000 claims description 16
- 239000008107 starch Substances 0.000 claims description 15
- 235000019698 starch Nutrition 0.000 claims description 15
- 235000019359 magnesium stearate Nutrition 0.000 claims description 13
- 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 10
- 229930195725 Mannitol Natural products 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 239000000594 mannitol Substances 0.000 claims description 10
- 235000010355 mannitol Nutrition 0.000 claims description 10
- 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 9
- 239000008101 lactose Substances 0.000 claims description 9
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 9
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 8
- 239000008187 granular material Substances 0.000 claims description 8
- 239000002245 particle Substances 0.000 claims description 8
- 239000008215 water for injection Substances 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 7
- 238000004132 cross linking Methods 0.000 claims description 7
- 239000003889 eye drop Substances 0.000 claims description 7
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 7
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 7
- 239000011230 binding agent Substances 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 5
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 5
- 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 claims description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 5
- 229960002233 benzalkonium bromide Drugs 0.000 claims description 5
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 5
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 5
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- 229960003943 hypromellose Drugs 0.000 claims description 5
- 239000000787 lecithin Substances 0.000 claims description 5
- 235000010445 lecithin Nutrition 0.000 claims description 5
- 229940067606 lecithin Drugs 0.000 claims description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 239000000741 silica gel Substances 0.000 claims description 5
- 229910002027 silica gel Inorganic materials 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims description 5
- 230000008961 swelling Effects 0.000 claims description 5
- 239000000853 adhesive Substances 0.000 claims description 4
- 230000001070 adhesive effect Effects 0.000 claims description 4
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 4
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 4
- 238000004945 emulsification Methods 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 239000000499 gel Substances 0.000 claims description 3
- 210000000214 mouth Anatomy 0.000 claims description 3
- 239000002002 slurry Substances 0.000 claims description 3
- 239000001488 sodium phosphate Substances 0.000 claims description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 239000011521 glass Substances 0.000 claims description 2
- 238000000227 grinding Methods 0.000 claims description 2
- 229960001855 mannitol Drugs 0.000 claims description 2
- 235000019890 Amylum Nutrition 0.000 claims 1
- 239000007788 liquid Substances 0.000 abstract description 5
- 239000007787 solid Substances 0.000 abstract description 5
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 238000003860 storage Methods 0.000 abstract description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000002421 anti-septic effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 239000002562 thickening agent Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 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 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000007919 dispersible tablet Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 201000007032 bacterial conjunctivitis Diseases 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- -1 dry Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 229940124307 fluoroquinolone Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 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
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 230000035699 permeability Effects 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
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a kind of Pharmaceutical composition containing besifloxacin or its salt, said composition exists with the form of moisture liquid preparation or solid preparation, convenient operation, transport and storage, applied range, applicable large-scale production.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, pharmaceutical preparation relating to besifloxacin and preparation method thereof.
Background technology
Besifloxacin is forth generation fluoroquinolone antibiotics, this novel quinolone medicine is except having has a broad antifungal spectrum, antibacterial activity is high, against gram-negative bacteria is active feature, also stronger antibacterial activity is had to gram positive bacteria, in particular improve the antibacterial activity to anaerobe, all have stronger effect to legionella, mycoplasma, chlamydia.Besifloxacin has good aqueous humor permeability, and this medicine is ratified to be used for the treatment of bacterial conjunctivitis abroad at present.
Summary of the invention
The invention provides a kind of Pharmaceutical composition containing besifloxacin or its salt, its salt comprises such as acid-addition salts example hydrochloric acid salt, acetate, phosphate, sulfate, nitrate, hydrobromate, lactate, citrate, tartrate, oxalates, maleate, fumarate, malate, mesylate, aspartate etc., and with the salt of alkali as sodium hydroxide, potassium hydroxide etc.
The Pharmaceutical composition of besifloxacin provided by the invention or its salt exists with the form of moisture liquid preparation or solid preparation, convenient operation, transport and storage, applied range, applicable large-scale production.
Described moisture liquid preparation composed as follows:
1) besifloxacin contained or its salt add with Micronised form, and its particle diameter is less than 10 μm;
2) containing pharmaceutically can adjuvant, comprise one or more of thickening agent, antiseptic, osmotic pressure regulator, pH adjusting agent, stabilizing agent and water;
3) thickening agent is selected from one or more mixture of hypromellose, hyaluronic acid sodium, carbomer, poloxamer;
4) antiseptic be selected from benzalkonium chloride, benzalkonium bromide, Metagin, second, third, one or more mixture of butyl ester;
5) osmotic pressure regulator is selected from one or more mixture of propylene glycol, glycerol, mannitol, sodium chloride, sodium bicarbonate, sodium citrate;
6) pH adjusting agent adopts sodium hydroxide, potassium hydroxide, aluminium hydroxide, triethanolamine etc.;
7) stabilizing agent adopts disodiumedetate, sodium sulfite, lecithin etc.
Described aqueous liquid preparation is prepared by following technique:
1) take 0.01 ~ 10% thickening agent and/or stabilizing agent to add suitable quantity of water fully swelling, then add the besifloxacin of 0.1% ~ 20% or its salt fully grinds or stirs or breast is even or ultrasonic, obtain solution I;
2) antiseptic, osmotic pressure regulator, stabilizing agent and/or thickening agent are added appropriate water dissolution, obtain solution II;
3) solution I and solution II merged, even or stir or ultrasonic method mix homogeneously by breast, adjusting agent adjust ph with pH is 5 ~ 7, then adds water to total amount.
Described aqueous liquid preparation is eye drop or gel for eye.
Described solid preparation composed as follows:
1) besifloxacin contained or its salt add with Micronised form or solvation form, and its particle diameter is less than 10 μm;
2) the pharmaceutically acceptable adjuvant contained, comprise in filler, disintegrating agent, wet adhesive, lubricant, effervescent, correctives, antioxidant, antiseptic one or more;
3) filler is selected from one or more in lactose, mannitol, starch, pre-paying starch, calcium hydrogen phosphate;
4) disintegrating agent is selected from one or more in low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, carboxymethylstach sodium, tween 80, Polyethylene Glycol;
5) wet adhesive is selected from one or more in water, ethanol, starch, hydroxypropyl cellulose, polyvinylpyrrolidone, methylcellulose;
6) lubricant is selected from one or more in magnesium stearate, Pulvis Talci, micropowder silica gel, silicon dioxide.The preparation technology of described solid preparation be get 0.1 ~ 20% besifloxacin or its salt mix homogeneously with 40% ~ 80% filler, 3% ~ 30% disintegrating agent, add suitable amount of adhesive granulate, dry, granulate, all the other adjuvants additional, mix homogeneously, compressed tablets or fill capsule.
Described solid preparation is tablet, dispersible tablet, oral cavity disintegration tablet or capsule.
Specific embodiment
The suspendible eye drop of embodiment 1 one kinds containing besifloxacin hydrochloride
Prescription:
| Supplementary material | Percentage ratio (%) |
| Besifloxacin hydrochloride | 0.8 |
| Hypromellose | 0.5 |
| Benzalkonium chloride | 0.01 |
| Mannitol | 0.05 |
| Sodium chloride | 0.5 |
| Sodium hydroxide | In right amount |
| Disodiumedetate | 0.01 |
Preparation technology:
1, aseptically, by hypromellose and appropriate water for injection 80 ~ 90 DEG C abundant swelling after, be cooled to room temperature, add besifloxacin hydrochloride grinding evenly, obtain solution I;
2, benzalkonium chloride, mannitol, sodium chloride, disodiumedetate are dissolved in appropriate water for injection successively, cross 0.2 μm of filter membrane, obtain solution II;
3, aseptically, solution I and solution II are merged, by high speed dispersing emulsification machine mix homogeneously, with 1M sodium hydroxide solution adjustment pH value to 5 ~ 7, then inject water to total amount;
4, under aseptic conditions, divide and be filled in sterilized eye drop bottle.
The gel for eye of embodiment 2 one kinds containing besifloxacin hydrochloride
Prescription:
| Supplementary material | Percentage ratio (%) |
| Besifloxacin hydrochloride | 0.6 2 --> |
| Hyaluronic acid sodium | 1.0 |
| Benzalkonium bromide | 0.01 |
| Dibastic sodium phosphate | 1 |
| Sodium hydroxide | In right amount |
| Lecithin | 0.01 |
Preparation method:
1, aseptically, get segment glass acid sodium and appropriate water for injection fully swelling after, add besifloxacin hydrochloride, lecithin stir, obtain solution I;
2, benzalkonium bromide, calcium hydrogen phosphate, residue hyaluronic acid sodium are dissolved in appropriate water for injection successively, cross 0.2 μm of filter membrane, obtain solution II;
3, aseptically, solution I and solution II are merged, by high speed dispersing emulsification machine mix homogeneously, with 1M sodium hydroxide solution adjustment pH value to 5 ~ 7, then inject water to total amount;
4, under aseptic conditions, divide and be filled in sterilized eye drop bottle.
The tablet of embodiment 3 one kinds containing besifloxacin hydrochloride
Prescription:
| Supplementary material | Percentage ratio (%) |
| Besifloxacin hydrochloride | 10 |
| Lactose | 60 |
| Dibastic sodium phosphate | 22 |
| Carboxymethylstach sodium | 5 |
| Starch | 2 |
| Magnesium stearate | 1 |
Preparation technology:
1, besifloxacin hydrochloride is mixed homogeneously with lactose, calcium hydrogen phosphate and carboxymethylstach sodium;
2, starch is made 10% starch slurry as binding agent, 18 mesh sieves are granulated;
3, particle drying is to moisture < 3.5%;
4,24 mesh sieve granulate, additional magnesium stearate, mix homogeneously;
5, tabletted.
The dispersible tablet of embodiment 4 one kinds containing besifloxacin hydrochloride
Prescription:
| Supplementary material | Percentage ratio (%) |
| Besifloxacin | 5 |
| Lactose | 58 |
| Starch | 30 |
| Cross-linking sodium carboxymethyl cellulose | 5 3 --> |
| Polyethylene glycol 6000 | 1 |
| Magnesium stearate | 1 |
Preparation technology:
1, besifloxacin is added appropriate dissolve with ethanol, and be scattered in lactose, after to be dried, obtain mixture I;
2, mixture I is mixed homogeneously with starch, cross-linking sodium carboxymethyl cellulose;
3, using water as wetting agent, 18 mesh sieves are granulated;
4, particle drying is to moisture < 3.5%;
5,24 mesh sieve granulate, additional polyethylene glycol 6000 and magnesium stearate, mix homogeneously;
6, tabletted.
The oral cavity disintegration tablet of embodiment 5 one kinds containing besifloxacin hydrochloride
Prescription:
| Supplementary material | Percentage ratio (%) |
| Besifloxacin hydrochloride | 6 |
| Mannitol | 50 |
| Microcrystalline Cellulose | 26 |
| Low-substituted hydroxypropyl cellulose (inside adding) | 8 |
| Polyvinylpyrrolidone | 1 |
| Low-substituted hydroxypropyl cellulose (additional) | 8 |
| Magnesium stearate | 1 |
Preparation technology:
1, besifloxacin hydrochloride is mixed homogeneously with mannitol, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose (inside adding);
2, make binding agent with the polyvinylpyrrolidone alcoholic solution of 3%, 18 mesh sieves are granulated;
3, particle drying is to moisture < 3.5%;
4,24 mesh sieve granulate, additional low-substituted hydroxypropyl cellulose (additional) and magnesium stearate, mix homogeneously;
5, tabletted.
The capsule of embodiment 6 one kinds containing besifloxacin hydrochloride
Prescription:
| Supplementary material | Percentage ratio (%) |
| Besifloxacin hydrochloride | 10 |
| Lactose | 50 |
| Starch | 30 |
| Cross-linking sodium carboxymethyl cellulose | 5 |
| Starch (binding agent) | 2 |
| Micropowder silica gel | 2 4 --> |
| Magnesium stearate | 1 |
Preparation technology:
1, besifloxacin hydrochloride is mixed homogeneously with lactose, starch, cross-linking sodium carboxymethyl cellulose;
2, make binding agent with 10% starch slurry, 20 mesh sieves are granulated;
3, particle drying is to moisture < 3.5%;
4,30 mesh sieve granulate, additional micropowder silica gel and magnesium stearate, mix homogeneously;
5, fill capsule.
Claims (4)
1. the suspendible eye drop containing besifloxacin hydrochloride, is characterized in that:
Preparation technology:
(1) aseptically, by hypromellose and appropriate water for injection 80 ~ 90 DEG C abundant swelling after, be cooled to room temperature, add besifloxacin hydrochloride grinding evenly, obtain solution I;
(2) benzalkonium chloride, mannitol, sodium chloride, disodiumedetate are dissolved in appropriate water for injection successively, cross 0.2 μm of filter membrane, obtain solution II;
(3) aseptically, solution I and solution II are merged, by high speed dispersing emulsification machine mix homogeneously, with 1M sodium hydroxide solution adjustment pH value to 5 ~ 7, then inject water to total amount;
(4) under aseptic conditions, divide and be filled in sterilized eye drop bottle.
2. the gel for eye containing besifloxacin hydrochloride, is characterized in that:
Preparation method:
(1) aseptically, get segment glass acid sodium and appropriate water for injection fully swelling after, add besifloxacin hydrochloride, lecithin stir, obtain solution I;
(2) benzalkonium bromide, calcium hydrogen phosphate, residue hyaluronic acid sodium are dissolved in appropriate water for injection successively, cross 0.2 μm of filter membrane, obtain solution II;
(3) aseptically, solution I and solution II are merged, by high speed dispersing emulsification machine mix homogeneously, with 1M sodium hydroxide solution adjustment pH value to 5 ~ 7, then inject water to total amount;
(4) under aseptic conditions, divide and be filled in sterilized eye drop bottle.
3. the oral cavity disintegration tablet containing besifloxacin hydrochloride, is characterized in that:
Preparation technology:
(1) by besifloxacin hydrochloride and mannitol, microcrystalline Cellulose, in add low-substituted hydroxypropyl cellulose and mix homogeneously;
(2) make binding agent with the polyvinylpyrrolidone alcoholic solution of 3%, 18 mesh sieves are granulated;
(3) particle drying is to moisture < 3.5%;
(4) 24 mesh sieve granulate, additional low-substituted hydroxypropyl cellulose and magnesium stearate, mix homogeneously;
(5) tabletted.
4. the capsule containing besifloxacin hydrochloride, is characterized in that:
Preparation technology:
(1) besifloxacin hydrochloride is mixed homogeneously with lactose, starch, cross-linking sodium carboxymethyl cellulose;
(2) make binding agent with 10% starch slurry, 20 mesh sieves are granulated;
(3) particle drying is to moisture < 3.5%;
(4) 30 mesh sieve granulate, additional micropowder silica gel and magnesium stearate, mix homogeneously;
(5) fill capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910244381.7A CN102114020B (en) | 2009-12-30 | 2009-12-30 | A kind of Pharmaceutical composition containing besifloxacin or its salt and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910244381.7A CN102114020B (en) | 2009-12-30 | 2009-12-30 | A kind of Pharmaceutical composition containing besifloxacin or its salt and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
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| CN102114020A CN102114020A (en) | 2011-07-06 |
| CN102114020B true CN102114020B (en) | 2016-04-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN200910244381.7A Active CN102114020B (en) | 2009-12-30 | 2009-12-30 | A kind of Pharmaceutical composition containing besifloxacin or its salt and preparation method thereof |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103565742A (en) * | 2012-07-25 | 2014-02-12 | 天津金耀集团有限公司 | Fluorometholone eye drops |
| CN102908323B (en) * | 2012-10-30 | 2015-03-04 | 天津红日药业股份有限公司 | Moxifloxacin-containing pharmaceutical composition |
| CN108815119B (en) * | 2018-08-10 | 2022-09-27 | 江苏亚邦爱普森药业有限公司 | Pharmaceutical composition containing besifloxacin hydrochloride and preparation method thereof |
| CN115708805A (en) * | 2022-11-21 | 2023-02-24 | 山东诺明康药物研究院有限公司 | Bexifloxacin hydrochloride in-situ gel eye drops and preparation method thereof |
| CN115919758A (en) * | 2022-11-21 | 2023-04-07 | 山东诺明康药物研究院有限公司 | Bexifloxacin hydrochloride ion sensitive in-situ gel eye drops and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101278905A (en) * | 2008-05-13 | 2008-10-08 | 山东博士伦福瑞达制药有限公司 | Ophthalmic composition containing natamycin, use and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010529133A (en) * | 2007-06-11 | 2010-08-26 | ボーシュ アンド ローム インコーポレイティド | Compositions and methods for modulating inflammation using fluoroquinolones |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101278905A (en) * | 2008-05-13 | 2008-10-08 | 山东博士伦福瑞达制药有限公司 | Ophthalmic composition containing natamycin, use and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| Efficacy and Safety of Besifloxacin Ophthalmic Suspension 0.6% in Pediatric Patients With Bacterial Conjunctivitis;Timothy L.等;《Optometry》;20090630;第80卷(第6期);第296-297页 * |
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| CN102114020A (en) | 2011-07-06 |
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Effective date of registration: 20201202 Address after: No. 279 Nanhai Road, Xiuying District 570314 Hainan city of Haikou Province Patentee after: AVENTIS PHARMA (HAINAN) Co.,Ltd. Address before: 100097, Wanquan mansion, 3 Jin Zhuang, Haidian District, Beijing, Sijiqing Patentee before: BEIJING D-VENTURE PHARMACEUTICAL TECHNOLOGY Corp. |
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Denomination of invention: A medicinal composition containing berxifloxacin or its salt and its preparation method Granted publication date: 20160420 Pledgee: Sanya Rural Commercial Bank Co.,Ltd. Pledgor: AVENTIS PHARMA (HAINAN) Co.,Ltd. Registration number: Y2024980014810 |
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