CN107522717A - A kind of lavo-ofloxacin hydrochloride crystal and combinations thereof - Google Patents
A kind of lavo-ofloxacin hydrochloride crystal and combinations thereof Download PDFInfo
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- CN107522717A CN107522717A CN201610451796.1A CN201610451796A CN107522717A CN 107522717 A CN107522717 A CN 107522717A CN 201610451796 A CN201610451796 A CN 201610451796A CN 107522717 A CN107522717 A CN 107522717A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/06—Peri-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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Abstract
The invention discloses a kind of lavo-ofloxacin hydrochloride crystal, structural formula is shown in formula I, the X ray powder diffractograms that described lavo-ofloxacin hydrochloride crystal is obtained using Cu K alpha ray measurements are as shown in Figure 1, the invention also discloses a kind of composition containing lavo-ofloxacin hydrochloride crystal, the stability of lavo-ofloxacin hydrochloride composition prepared by the present invention is preferable, particle is uniform, during Levofloxacin Tablet is prepared, easily mixed with other auxiliary materials, the disintegration time of the tablet is short, stripping quantity is big, wettability is small, active component is stable, bioavilability improves, the present invention is also prepared for a kind of new lavo-ofloxacin hydrochloride crystal, so that the stability increase of Levofloxacin Tablet, and preparation technology provided by the invention is simple, it is easily-controllable, production efficiency is high, energy consumption is low.
Description
Technical field
The invention belongs to pharmaceutical technology field, specifically, is related to a kind of lavo-ofloxacin hydrochloride crystal and combinations thereof.
Background technology
Ofloxacin is with 1 by the L- isomers of high antibacterial activity and the D- isomers of low antibacterial activity:1 composition of proportions
Racemic mixture, the external activity of lavo-ofloxacin is 2 times of racemic modification, is 8-128 times of d-isomer, and the secondary work of poison
With smaller, lavo-ofloxacin is the active ingredient levo form in Ofloxacin (racemization), and its mechanism of action, antibacterial action feature are same
Ofloxacin, but its antibacterial action is slightly strong compared with Ofloxacin, lavo-ofloxacin can suppress DNA gyrases, the duplication of blocking dna,
Bacterium produces bacteriolyze in higher than minimum inhibitory concentration several times environment, and lavo-ofloxacin has really to Grain-positive and negative bacteria
The vitro antibacterial activity cut, lavo-ofloxacin are far longer than gram positive bacteria to the antibacterial action of gram negative bacilli, and its is external
Antibacterial action is slightly strong or similar compared with Norfloxacin, and the two antimicrobial spectrum is identical, has to the extremely sensitive pathogenic bacteria of lavo-ofloxacin：Leather
Blue negative bacillus and part gram positive bacteria, such as staphylococcus aureus, gonococcus, legion brevibacterium, to lavo-ofloxacin
More sensitive pathogenic bacteria have：Pseudomonas aeruginosa (Pseudomonas aeruginosa), streptococcus etc., clinic is usually used in infection in respiratory system, secreted
Urogenital system system, biliary tract, enteric infection, skin soft-tissue infection and the treatment of other infection, work well.
Lavo-ofloxacin is fully synthetic the 3rd generation promise ketone broad-spectrum high efficacy antimicrobial, and antimicrobial spectrum is extensively and effect is strong,
The disease that treatment is infected by bacterial thus is largely used to, there is good clinical effectiveness.But its water solubility is poor, biological utilisation
Degree is not high, and the lavo-ofloxacin formulation listed at present is mainly conventional tablet, capsule, injection.
Publication number CN102784121A discloses a kind of lavo-ofloxacin composition freeze-drying oral disnitegration tablet and its preparation side
Method, it is related to the preparation method technical field of medicine and medicine, mainly solves the ordinary preparation of lavo-ofloxacin in the prior art, treats
Effect is poor, the problem of not being suitable for children, and swallow the patient medication having any problem, prepares lavo-ofloxacin composition freeze-drying oral cavity
Disintegrated tablet each component and each group dosis refracta ratio are：Lavo-ofloxacin 10%-24% parts by weight, mannitol 24%-50% parts by weight,
Gelatin 2%-4% parts by weight, medium substitution value hydroxypropyl-beta-schardinger dextrin 32%-74% parts by weight, Sucralose 0.1%-
0.2% parts by weight, the parts by weight of purified water 50%.Although the lyophilized oral disnitegration tablet disintegration rate is fast, drug absorption is abundant, takes
Convenient, but its preparation method is complicated, unsuitable industrialized production, long-time storage, Orally disintegrating tablet stability is poor, during disintegration
Between extend, quality is unstable.
Publication number CN103520124A discloses a kind of Levofloxacin Tablet and preparation method thereof, said preparation be by
Medicine-containing particle and citric acid enteric coated particles and lubricant mix tabletting and formed, described citric acid enteric coated particles be by citric acid and
The dissolving of polyvinyl acetate phthalic acid ester is dried and obtained in ethanol, and the invention does not dissolve under one's belt, the dissolving release Chinese holly in intestines
Rafter acid, reduces intestinal juice basicity, ensure that lavo-ofloxacin hydrochloride does not separate out, improve the bioavilability of medicine, but its is steady
Qualitative difference, it is unfavorable for storing.
" orthogonal design optimizes the formulation and technology of levofloxacin hydrochloride tablets "【Zhou Chenglin, Zhang Yi, Xu Jie, Yu Chunmei, Zheng are small
Peak, Wu Qiang, medical science and technology [J]】Disclose a kind of tablet formulation of levofloxacin hydrochloride tablets, lavo-ofloxacin hydrochloride 100g,
Microcrystalline cellulose 80g, starch 30g, 5% starch slurry is appropriate, Ac-Di-Sol 15g, magnesium stearate 1g, is made
1000, it is coated with Opadry 85G62651, microcrystalline cellulose, starch are filler, in addition, microcrystalline cellulose also has concurrently
There are adhesive, disintegrant, Ac-Di-Sol is as outer disintegrant, using 5% starch slurry as adhesive,
Magnesium stearate, because microcrystalline cellulose has good hygroscopicity, can make tablets do swell and softening, therefore discomfort as lubricant
Share in coating tablet, in addition the magnesium ion in magnesium stearate easily with 3 carboxyls in lavo-ofloxacin hydrochloride medicines structure and 4
Ketone carboxyl forms chelate, reduces medicine antibacterial activity.
It is dispersible tablet that the research and development for the lavo-ofloxacin hydrochloride compound preparation studied at present are more, hydrochloric acid levofloxacin
The bioavilability of star is not high, and maintenance efficacy time is short, and stability is poor, is unfavorable for storing for a long time, and preparation method is complicated, is not suitable for
Industrialized production.
For these reasons, it is special to propose the present invention.
The content of the invention
The technical problem to be solved in the present invention is overcome the deficiencies in the prior art, there is provided a kind of lavo-ofloxacin hydrochloride
Composition, said composition have preferable stability, and dissolution rate is fast, and disintegration rate is fast, and bioavilability is high, epigranular,
It is easy to mixing and tabletting.
The first object of the present invention provides a kind of lavo-ofloxacin hydrochloride crystal, structural formula shown in formula I, described salt
The X-ray powder diffraction spectrogram that sour lavo-ofloxacin crystal is obtained using Cu-K alpha ray measurements is as shown in Figure 1：
Because solid kind medicine has a polymorphism, solid drugs of the same race, it both can be with unformed presence, can also be with
The polymorphic of different crystal structure forms is present, and the different crystal formation of same medicine may be in the side such as solubility, heat endurance
Significant difference be present in face, the X-ray powder diffraction of lavo-ofloxacin hydrochloride crystal of the present invention 2 θ be 5.83 °, 10.79 °,
14.69 °, 20.81 °, 25.42 °, 31.04 ° show characteristic peak.
Further, the preparation method of described lavo-ofloxacin hydrochloride crystal is as follows：At 30 DEG C, by the left oxygen fluorine of hydrochloric acid
In the in the mixed solvent of water, acetone and dichloromethane, described water, acetone, the volume ratio of dichloromethane are husky star dissolving crude product
3-4：1：2-3, then stirring and dissolving, stir speed (S.S.) 8-12rmp, stirs 35-40min, is then cooled to -18 DEG C~-15 DEG C,
Crystallization is stood, filtering, is 75 DEG C of -78 DEG C of dryings in temperature, obtains described lavo-ofloxacin hydrochloride crystal.
The results showed in the case of prescription and preparation method identical, the hydrochloric acid levofloxacin of the invention prepared is utilized
The composition of star Crystallization, there is preferable stability.
The second object of the present invention provides a kind of composition containing described lavo-ofloxacin hydrochloride crystal.
Further, the composition includes following composition：
Further, the composition includes following composition：
The present invention is using starch and lactose as filler, and lactose is a kind of excellent tablet filler, by bovine whey
Extraction is made, and its property is stable, and no hygroscopicity, compressibility is good, and the tablet being pressed into is bright and clean attractive in appearance, the present invention use polyethylene glycol for
Lubricant, polyethylene glycol have a good lubricant effect, and the disintegration and dissolution of tablet are unaffected.
The preparation method of the coating tablet of said composition is as follows：
(1) preparation of adhesive：Hydroxypropyl cellulose, hydroxypropyl methyl cellulose and the purified water of recipe quantity is taken to be configured to
1%-3% binder solution, it is standby；
(2) lavo-ofloxacin hydrochloride bulk drug, starch and lactose have been weighed according to recipe quantity and has put into wet granulator together
It is interior, stirring key mixing is opened, the binder solution that step (1) obtains is poured into mixed supplementary material, softwood is made, continues to stir
Mix, particle then is made in softwood with granulating cutter；
(3) manufactured particle is transferred into boiling drier to dry, it is by dried pellet through sieves whole grain, whole whole grains are good
Dry particle and load weighted additional auxiliary material polyethylene glycol and sodium carboxymethyl starch all put into Mixers with Multi-direction Movement,
Open mixing key progress particle to be well mixed, by the particle mixed rotary pelleting machine tabletting；
(4) substrate after tabletting is coated, that is, obtains Levofloxacin Tablet.
Further, the composition includes following composition：
Further, the composition includes following composition：
Prepared by filler in said composition selects microcrystalline cellulose the to be partial hydrolysis less crystallinity of the degree of polymerization
Cellulose, there is good compressibility, there is stronger cohesive force, the tablet being pressed into has larger hardness, and this composition uses carboxylic
Methyl starch sodium is adhesive, when sodium carboxymethyl starch can improve the disintegration of Levofloxacin Tablet as adhesive
Between, increase dissolution rate.
The preparation method of the coating tablet of said composition is as follows：
(1) adhesive is prepared：Sodium carboxymethyl starch, purified water is taken to be configured to 1% CMS sodium solution, it is standby.
(2) pelletize：Lavo-ofloxacin bulk drug, microcrystalline cellulose, starch have been weighed in prescription ratio, has put into wet method together
In granulator, stirring key mixing is opened, the binder solution prepared is poured into mixed supplementary material, softwood is made, continue to stir
Mix, particle finally is made in softwood with granulating cutter.
(3) dry：The particle pelletized is transferred to boiling drier drying.
(4) whole grain：By dried pellet through sieves whole grain.
(5) it is total mixed：By the good dry particle of whole whole grains and load weighted additional auxiliary material sodium carboxymethyl starch, magnesium stearate
All put into Mixers with Multi-direction Movement, open mixing key progress particle and be well mixed.
(6) tabletting：The rotary pelleting machine tabletting of mixed particle.
(7) coating solution is prepared：Film coating pre-mix dose valency such as purified water is taken to be configured to film coating liquid.
(8) it is coated：Film coating.
(9) wrapped in：Packed with Aluminium-coating Packer.
(10) be put in storage：After the assay was approved, finished product is put in storage.
Further, described composition is Levofloxacin Tablet.
Described Levofloxacin Tablet is coating tablet.
Further, the coating of coating tablet is made up of following composition：
Gastric solubility acrylic resin IV 22-25 parts by weight
Percent by volume is 90% ethanol 236-247 parts by weight.
Using technical scheme, have the beneficial effect that：The present invention is prepared for a kind of new lavo-ofloxacin hydrochloride
Crystal so that the stability increase of Levofloxacin Tablet, and preparation technology provided by the invention is simple, easily-controllable, raw
Production efficiency high, energy consumption are low, and the stability of lavo-ofloxacin hydrochloride composition prepared by the present invention is preferable, and particle is uniform,
During preparing Levofloxacin Tablet, easily mixed with other auxiliary materials, the disintegration time of the tablet is short, stripping quantity
Greatly, wettability is small, and active component is stable, and bioavilability improves.
Brief description of the drawings
The X-ray powder diffraction figure of the lavo-ofloxacin hydrochloride crystal of Fig. 1 embodiment of the present invention 1；
Levofloxacin Tablet Dissolution profiles in Fig. 2 test examples 1 of the present invention.
Embodiment
Embodiment 1
At 30 DEG C, by lavo-ofloxacin hydrochloride dissolving crude product water, acetone and dichloromethane in the mixed solvent, it is described
Water, acetone, dichloromethane volume ratio be 3：1：2, then stirring and dissolving, stir speed (S.S.) 8rmp, stirs 35min, then
- 18 DEG C are cooled to, stands crystallization, filtering, is 75 DEG C of dryings in temperature, obtains described lavo-ofloxacin hydrochloride crystal.
Obtained lavo-ofloxacin hydrochloride crystal is using the X-ray powder diffraction spectrogram that Cu-K alpha ray measurements obtain as schemed
Shown in 1.The X-ray powder diffraction of lavo-ofloxacin hydrochloride crystal 2 θ be 5.83 °, 10.79 °, 14.69 °, 20.81 °,
25.42 °, 31.04 ° show characteristic peak.
Embodiment 2
At 30 DEG C, by lavo-ofloxacin hydrochloride dissolving crude product water, acetone and dichloromethane in the mixed solvent, it is described
Water, acetone, dichloromethane volume ratio be 4：1：3, then stirring and dissolving, stir speed (S.S.) 10rmp, stirs 38min, then
- 16 DEG C are cooled to, stands crystallization, filtering, is 76 DEG C of dryings in temperature, obtains described lavo-ofloxacin hydrochloride crystal.
The X-ray powder diffraction spectrogram and reality that obtained lavo-ofloxacin hydrochloride crystal is obtained using Cu-K alpha ray measurements
It is basically identical to apply example 1.
Embodiment 3
At 30 DEG C, by lavo-ofloxacin hydrochloride dissolving crude product water, acetone and dichloromethane in the mixed solvent, it is described
Water, acetone, dichloromethane volume ratio be 3.5：1：2, then stirring and dissolving, stir speed (S.S.) 12rmp, stirs 40min, so
After be cooled to -15 DEG C, stand crystallization, filtering, be 78 DEG C of dryings in temperature, obtain described in lavo-ofloxacin hydrochloride crystal.
The X-ray powder diffraction spectrogram and reality that obtained lavo-ofloxacin hydrochloride crystal is obtained using Cu-K alpha ray measurements
It is basically identical to apply example 1.
Embodiment 4
The prescription of Levofloxacin Tablet：
It is coated prescription：
The preparation method of Levofloxacin Tablet：
(1) preparation of adhesive：Hydroxypropyl cellulose, hydroxypropyl methyl cellulose and the purified water of recipe quantity is taken to be configured to
1% binder solution, it is standby；
(2) lavo-ofloxacin hydrochloride bulk drug, starch and lactose have been weighed according to recipe quantity and has put into wet granulator together
It is interior, stirring key mixing is opened, the binder solution that step (1) obtains is poured into mixed supplementary material, softwood is made, continues to stir
Mix, particle then is made in softwood with granulating cutter；
(3) manufactured particle is transferred into boiling drier to dry, it is by dried pellet through sieves whole grain, whole whole grains are good
Dry particle and load weighted additional auxiliary material polyethylene glycol and sodium carboxymethyl starch all put into Mixers with Multi-direction Movement,
Open mixing key progress particle to be well mixed, by the particle mixed rotary pelleting machine tabletting；
(4) substrate after tabletting is coated, that is, obtains lavo-ofloxacin hydrochloride coating tablet.
Embodiment 5
The prescription of Levofloxacin Tablet：
It is coated prescription：
The preparation method of Levofloxacin Tablet：
(1) preparation of adhesive：Hydroxypropyl cellulose, hydroxypropyl methyl cellulose and the purified water of recipe quantity is taken to be configured to
2% binder solution, it is standby；
(2) lavo-ofloxacin hydrochloride bulk drug, starch and lactose have been weighed according to recipe quantity and has put into wet granulator together
It is interior, stirring key mixing is opened, the binder solution that step (1) obtains is poured into mixed supplementary material, softwood is made, continues to stir
Mix, particle then is made in softwood with granulating cutter；
(3) manufactured particle is transferred into boiling drier to dry, it is by dried pellet through sieves whole grain, whole whole grains are good
Dry particle and load weighted additional auxiliary material polyethylene glycol and sodium carboxymethyl starch all put into Mixers with Multi-direction Movement,
Open mixing key progress particle to be well mixed, by the particle mixed rotary pelleting machine tabletting；
(4) substrate after tabletting is coated, that is, obtains lavo-ofloxacin hydrochloride coating tablet.
Embodiment 6
The prescription of Levofloxacin Tablet：
It is coated prescription：
The preparation method of Levofloxacin Tablet：
(1) preparation of adhesive：Hydroxypropyl cellulose, hydroxypropyl methyl cellulose and the purified water of recipe quantity is taken to be configured to
3% binder solution, it is standby；
(2) lavo-ofloxacin hydrochloride bulk drug, starch and lactose have been weighed according to recipe quantity and has put into wet granulator together
It is interior, stirring key mixing is opened, the binder solution that step (1) obtains is poured into mixed supplementary material, softwood is made, continues to stir
Mix, particle then is made in softwood with granulating cutter；
(3) manufactured particle is transferred into boiling drier to dry, it is by dried pellet through sieves whole grain, whole whole grains are good
Dry particle and load weighted additional auxiliary material polyethylene glycol and sodium carboxymethyl starch all put into Mixers with Multi-direction Movement,
Open mixing key progress particle to be well mixed, by the particle mixed rotary pelleting machine tabletting；
(4) substrate after tabletting is coated, that is, obtains lavo-ofloxacin hydrochloride coating tablet.
Embodiment 7
The prescription of Levofloxacin Tablet：
It is coated prescription：
The preparation method of Levofloxacin Tablet：
(1) adhesive is prepared：Sodium carboxymethyl starch, purified water is taken to be configured to 1% CMS sodium solution, it is standby.
(2) pelletize：Lavo-ofloxacin bulk drug, microcrystalline cellulose, starch have been weighed in prescription ratio, has put into wet method together
In granulator, stirring key mixing is opened, the binder solution prepared is poured into mixed supplementary material, softwood is made, continue to stir
Mix, particle finally is made in softwood with granulating cutter.
(3) dry：The particle pelletized is transferred to boiling drier drying.
(4) whole grain：By dried pellet through sieves whole grain.
(5) it is total mixed：By the good dry particle of whole whole grains and load weighted additional auxiliary material sodium carboxymethyl starch, magnesium stearate
All put into Mixers with Multi-direction Movement, open mixing key progress particle and be well mixed.
(6) tabletting：The rotary pelleting machine tabletting of mixed particle.
(7) coating solution is prepared：Film coating pre-mix dose valency such as purified water is taken to be configured to film coating liquid.
(8) it is coated：Film coating.
(9) wrapped in：Packed with Aluminium-coating Packer.
(10) be put in storage：After the assay was approved, finished product is put in storage.
Embodiment 8
The prescription of Levofloxacin Tablet：
It is coated prescription：
The preparation method of Levofloxacin Tablet：
(1) adhesive is prepared：Sodium carboxymethyl starch, purified water is taken to be configured to 1% CMS sodium solution, it is standby.
(2) pelletize：Lavo-ofloxacin bulk drug, microcrystalline cellulose, starch have been weighed in prescription ratio, has put into wet method together
In granulator, stirring key mixing is opened, the binder solution prepared is poured into mixed supplementary material, softwood is made, continue to stir
Mix, particle finally is made in softwood with granulating cutter.
(3) dry：The particle pelletized is transferred to boiling drier drying.
(4) whole grain：By dried pellet through sieves whole grain.
(5) it is total mixed：By the good dry particle of whole whole grains and load weighted additional auxiliary material sodium carboxymethyl starch, magnesium stearate
All put into Mixers with Multi-direction Movement, open mixing key progress particle and be well mixed.
(6) tabletting：The rotary pelleting machine tabletting of mixed particle.
(7) coating solution is prepared：Film coating pre-mix dose valency such as purified water is taken to be configured to film coating liquid.
(8) it is coated：Film coating.
(9) wrapped in：Packed with Aluminium-coating Packer.
(10) be put in storage：After the assay was approved, finished product is put in storage.
Embodiment 9
The prescription of Levofloxacin Tablet：
It is coated prescription：
The preparation method of Levofloxacin Tablet：
(1) adhesive is prepared：Sodium carboxymethyl starch, purified water is taken to be configured to 1% CMS sodium solution, it is standby.
(2) pelletize：Lavo-ofloxacin bulk drug, microcrystalline cellulose, starch have been weighed in prescription ratio, has put into wet method together
In granulator, stirring key mixing is opened, the binder solution prepared is poured into mixed supplementary material, softwood is made, continue to stir
Mix, particle finally is made in softwood with granulating cutter.
(3) dry：The particle pelletized is transferred to boiling drier drying.
(4) whole grain：By dried pellet through sieves whole grain.
(5) it is total mixed：By the good dry particle of whole whole grains and load weighted additional auxiliary material sodium carboxymethyl starch, magnesium stearate
All put into Mixers with Multi-direction Movement, open mixing key progress particle and be well mixed.
(6) tabletting：The rotary pelleting machine tabletting of mixed particle.
(7) coating solution is prepared：Film coating pre-mix dose valency such as purified water is taken to be configured to film coating liquid.
(8) it is coated：Film coating.
(9) wrapped in：Packed with Aluminium-coating Packer.
(10) be put in storage：After the assay was approved, finished product is put in storage.
The dissolution determination of test example 1
Levofloxacin Tablet prepared by the embodiment 1 of investigational agent 1；
Levofloxacin Tablet prepared by the embodiment 7 of investigational agent 2；
The Levofloxacin Tablet that comparison medicine 1 is prepared according to embodiment 1 in patent CN103520124A；
Comparison medicine 2 is according to " orthogonal design optimizes the formulation and technology of levofloxacin hydrochloride tablets "【Zhou Chenglin, Zhang Yi, Xu Jie,
Yu Chunmei, Zheng little Feng, Wu Qiang, medical science and technology [J]】In prescription prepare Levofloxacin Tablet.
3 comparison medicines of comparison medicine are identical with the Levofloxacin Tablet of investigational agent 1, difference, by investigational agent 1
Lavo-ofloxacin hydrochloride crystal replace with lavo-ofloxacin bulk drug；
4 comparison medicines of comparison medicine are identical with the Levofloxacin Tablet of investigational agent 2, difference, by investigational agent 2
Lavo-ofloxacin hydrochloride crystal replace with lavo-ofloxacin bulk drug
This test example be to investigational agent and comparison medicine preparation ofloxacin hydrochloride tablet agent according to《Chinese Pharmacopoeia》2005 editions
Second method of annex XC second determines dissolution rate, and using hydrochloric acid solution (9-1000ml) 1000ml as solvent, rotating speed is per minute 50
Turn, 37 DEG C ± 0.5 DEG C of temperature, determine in accordance with the law, respectively at 10,20,30,40,50,60,70,80min samplings, ultraviolet-visible point
Light photometry (second annex IV of China's coastal port) determines trap at 258nm, calculates dissolution rate, as a result as schemed
Shown in 2.
Figure it is seen that ofloxacin hydrochloride tablet agent prepared by the present invention has higher dissolution compared with comparison medicine
Degree, the dissolution rate of ofloxacin hydrochloride tablet agent prepared by the ofloxacin hydrochloride crystal prepared using the present invention is higher, shows to give birth to
Thing availability is high, has more preferable bactericidal property.
Above-mentioned experiment has also been carried out to the Levofloxacin Tablet prepared by other embodiments of the present invention, what it was obtained
As a result it is similar.
The disintegration time of test example 2 determines
According to disintegration time inspection technique (two annex XA of Chinese Pharmacopoeia version in 2010), the stainless steel that hanging basket is passed through into upper end
Axle suspension is hung on metallic support, is immersed in 1000ml beakers, and adjusts when hanging basket position makes its decline screen cloth away from beaker bottom
23mm, the water that temperature is 37 ± 1 DEG C is filled in beaker, screen cloth is at the 15mm of underwater when hanging basket rises when adjusting height of water level.
Disintegration time is as shown in table 1：
The disintegration time of table 1
| Test drug | Disintegration time (s) |
| Investigational agent 1 | 1.0 |
| Investigational agent 2 | 0.9 |
| Comparison medicine 1 | 18 |
| Comparison medicine 2 | 21 |
| Comparison medicine 3 | 17 |
| Comparison medicine 4 | 18 |
Note：Each investigational agent and comparison medicine are the same as test example 1.
The disintegration time of Levofloxacin Tablet of the invention is good compared with comparison medicine as can be seen from Table 1, faster
Have the function that drug effect, the tablet prepared using the lavo-ofloxacin hydrochloride crystal of the present invention is had more preferably than common bulk drug
Disintegration time.
Above-mentioned experiment has also been carried out to the Levofloxacin Tablet prepared by other embodiments of the present invention, what it was obtained
As a result it is similar.
The stability test of test example 3
By the product for preparing of investigational agent 1, investigational agent 2, comparison medicine 1 and comparison medicine 2 of the present invention different temperatures, humidity,
Investigated under the influence factors such as illumination, determine indices, be shown in Table 2.
The wettability of table 2 is tested
Note：Each investigational agent and comparison medicine are the same as test example 1.
From the results shown in Table 2, under conditions of different temperature, humidity, illumination, in sample produced by the present invention
Wettability is significantly less than the wettability of comparison medicine, illustrates that the quality of Levofloxacin Tablet prepared by the present invention is more steady
It is fixed, controllable.
Above-mentioned experiment has also been carried out to the Levofloxacin Tablet prepared by other embodiments of the present invention, what it was obtained
As a result it is similar.
Embodiment in above example can be further combined or replace, and embodiment is only to the present invention's
Preferred embodiment is described, and not the spirit and scope of the present invention are defined, and is not departing from design philosophy of the present invention
Under the premise of, various changes and modifications that professional and technical personnel in the art make to technical scheme belong to this hair
Bright protection domain.
Claims (10)
- A kind of 1. lavo-ofloxacin hydrochloride crystal, it is characterised in that structural formula shown in formula I, described lavo-ofloxacin hydrochloride The X-ray powder diffraction spectrogram that crystal is obtained using Cu-K alpha ray measurements is as shown in Figure 1：
- A kind of 2. preparation method of the lavo-ofloxacin hydrochloride crystal described in claim 1, it is characterised in that described preparation side Method comprises the following steps：At 30 DEG C, by lavo-ofloxacin hydrochloride dissolving crude product water, acetone and dichloromethane mixed solvent In, described water, acetone, the volume ratio of dichloromethane are 3-4：1：2-3, then stirring and dissolving, stir speed (S.S.) 8-12rmp, 35-40min is stirred, is then cooled to -18 DEG C~-15 DEG C, crystallization is stood, filtering, is 75 DEG C of -78 DEG C of dryings in temperature, obtains Described lavo-ofloxacin hydrochloride crystal.
- It is 3. a kind of containing the composition for having the right to want the lavo-ofloxacin hydrochloride crystal described in 1.
- 4. composition according to claim 3, it is characterised in that including following composition：
- 5. composition according to claim 3, it is characterised in that including following composition：
- 6. composition according to claim 3, it is characterised in that including following composition：
- 7. composition according to claim 6, it is characterised in that including following composition：
- 8. according to the composition described in claim 4-7 any one, it is characterised in that described composition is the left oxygen fluorine of hydrochloric acid Husky star tablet.
- 9. composition according to claim 8, it is characterised in that described Levofloxacin Tablet is coating tablet.
- 10. Levofloxacin Tablet according to claim 9, it is characterised in that the coating of coating tablet by as follows into It is grouped into：Gastric solubility acrylic resin IV 22-25 parts by weightPercent by volume is 90% ethanol 236-247 parts by weight.
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| CN201610451796.1A CN107522717A (en) | 2016-06-20 | 2016-06-20 | A kind of lavo-ofloxacin hydrochloride crystal and combinations thereof |
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| CN201610451796.1A CN107522717A (en) | 2016-06-20 | 2016-06-20 | A kind of lavo-ofloxacin hydrochloride crystal and combinations thereof |
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| CN112279866A (en) * | 2020-11-24 | 2021-01-29 | 辽宁药联制药有限公司 | Levofloxacin hydrochloride polymorphic substance and preparation method thereof |
| CN113398082A (en) * | 2021-06-23 | 2021-09-17 | 海南海神同洲制药有限公司 | Levofloxacin hydrochloride tablet and preparation method thereof |
| CN114891024A (en) * | 2021-08-03 | 2022-08-12 | 青岛市食品药品检验研究院（青岛市药品不良反应监测中心、青岛市实验动物和动物实验中心） | Levofloxacin-nicotinic acid pharmaceutical co-crystal and preparation method thereof |
| CN115501232A (en) * | 2022-08-26 | 2022-12-23 | 成都锦华药业有限责任公司 | Norfloxacin composition and preparation method of preparation thereof |
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| CN112279866A (en) * | 2020-11-24 | 2021-01-29 | 辽宁药联制药有限公司 | Levofloxacin hydrochloride polymorphic substance and preparation method thereof |
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| CN115501232A (en) * | 2022-08-26 | 2022-12-23 | 成都锦华药业有限责任公司 | Norfloxacin composition and preparation method of preparation thereof |
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