CN107343879A

CN107343879A - Balofloxacin pharmaceutical composition, preparation method and applications

Info

Publication number: CN107343879A
Application number: CN201610286343.8A
Authority: CN
Inventors: 刘保珍; 陶邵颖; 刘佳; 刘祥伟; 章莉; 王清平; 耿晓慈; 沈方; 陈双双; 邓道君; 王姗姗; 左霜; 吴嘉忆; 吴宇蓉; 张瑱; 王涛; 吴苗; 卓嘉和; 李芳全
Original assignee: YUNG SHIN PHARM IND (KUNSHAN) CO Ltd
Current assignee: YUNG SHIN PHARM IND (KUNSHAN) CO Ltd
Priority date: 2016-05-04
Filing date: 2016-05-04
Publication date: 2017-11-14

Abstract

The invention discloses a kind of Balofloxacin pharmaceutical composition, preparation method and applications, the Balofloxacin pharmaceutical composition includes each component by Balofloxacin pharmaceutical composition total weight percent：Balofloxacin 40~80%, filler 15~40%, adhesive 0~10%, disintegrant 0~10% and lubricant 0~10%, this Balofloxacin pharmaceutical composition optimizes the proportioning shared by each component, technique is simple, it is easy to production to amplify, dissolution is rapid in vivo, clinical effectiveness is good, and can be used in preparing the pharmaceutical preparation of prevention and treatment simple form urinary tract infections, pelvic inflammation and Cervicitis as caused by sensitive bacteria.

Description

Balofloxacin pharmaceutical composition, preparation method and applications

Technical field

The present invention relates to a kind of Balofloxacin pharmaceutical composition, preparation method and applications, Belong to pharmaceutical technology field.

Background technology

It is acidum nalidixicum (Nalidixic Acid) that first, which is used for clinical QNS, It is first generation QNS, due to this Oral drug absorption difference and side effect It is more, do not have to.Second generation QNS is pipemidic acid (Pipemidic Acid), Urinary tract infections, enteric infection for sensitive bacteria etc..QNS is by clinic Give one's full attention to and start from 1979, synthesized Norfloxacin (Norfloxacin) at that time, this It is the beginning of third generation QNS.Due to introducing fluorine atom on its parent nucleus, So that the antibacterial activity of Norfloxacin greatly improves while side effect substantially reduces, Clinically obtain more and more extensive application.Hereafter a series of fluorine-containing quinoline promises have been synthesized Ketone medicine, i.e. third generation QNS, as Pefloxacin, Ciprofloxacin, Enoxacin, Ofloxacin etc..Hereafter it is husky and to occur Lomefloxacin, support fluorine in succession The new third generation QNS such as star, gatifloxacin, their antibacterial action or Pharmacokinetics performance has further improvement again.In recent years, and constantly there is new Three generations's QNS lists, and the height that they had both remained resisting gram-positive bacteria is living Property feature, clearly enhances the activity of anti-Gram-negative bacteria again, and to anaerobic bacteria, Mycoplasma, Chlamydia etc. also have effect.Balofloxacin is exactly one of this kind of medicine.

Balofloxacin is fluoroquinolone antibacterial agent, and its antibacterial action comes from interference DNA helicases necessary to DNA of bacteria synthesis, it is not only to Gram-negative bacteria Effectively, MRSA is included to gram-positive bacteria, streptococcus pneumonia also has very strong resist Bacterium activity, especially to clinically refractory by bacillus fragilis (B.fragilis), homeliness type Psoriasis (P.vulgaris), Clestridium difficile (C.difficile), digestion chain Coccus (Peptostretococcus) etc. is bacterial infected with stronger therapeutic effect. The physical characteristic of Balofloxacin is shown as white or off-white powder, and its is odorless, bitter； It is readily soluble in glacial acetic acid, alcohol is slightly soluble in, it is insoluble in water or ethyl acetate, Dissolved in 0.1mol/L hydrochloric acid solutions, in methanol or 0.1mol/l sodium hydroxide solutions It is slightly molten.Conventional Balofloxacin has two kinds of forms, and a kind of is two hydrations with the crystallization water Balofloxacin, another kind are the Balofloxacins of nodeless mesh water.

Pelvic inflammation refer to female pelvic cavity reproductive organs, periuterine connective tissue and The inflammation of pelvic peritoneum, wherein chronic pelvic inflammation are often that acute stages treated is not thorough Delay, its disease time length, the state of an illness are more obstinate.Cervicitis is the common disease of gynaecology One of disease, including portio vaginalis cervicis inflammation and canal of uterine cervix mucosal inflammation, factor palace Neck tube portio vaginalis scaly epithelium mutually continues with vagina squamous, and colpitis can cause son Ectocervical inflammation, and because canal of uterine cervix mucosal epithelium is simple columnar epithelium, Anti-infection ability is poor, easily infects；Clinical common cervicitis is anxious at present Proliferative cervical pipe mucositis, if acute cervicitis is held without timely diagnosis and treatment or pathogen Renew, chronic cervicitis disease can be caused.Both the above disease is not specific Chemical drug is treated, mostly treatment by Chinese herbs, and such as FUKE QIANJIN PIAN treatment cervicitis, safflower is such as Ball of anticipating treats chronic pelvic inflammation etc..Therefore need one kind can curative effect can well control Treat the chemical drug of above two disease.

The content of the invention

First technical problem to be solved by this invention is provided for the state of the art The Balofloxacin medicine that dissolution is rapid, In vitro-in vivo correlation is good, clinical effectiveness is good in vivo Composition.

Second technical problem to be solved by this invention be to provide a kind of technique it is simple, Yield is high, is easy to the preparation method of the Balofloxacin pharmaceutical composition of production amplification.

3rd technical problem to be solved by this invention is to provide a kind of Balofloxacin medicine Compositions prepare prevention and treatment the simple form urinary tract infections as caused by sensitive bacteria, Application in the pharmaceutical preparation of pelvic inflammation and Cervicitis.

Technical scheme is used by the present invention solves above-mentioned first technical problem：

A kind of Balofloxacin pharmaceutical composition, including following press Balofloxacin drug regimen The each component of thing percentage by weight meter：

Balofloxacin 40~80%, for example, 42%, 44%, 46%, 48%, 50%, 52%th, 54%, 56%, 58%, 60%, 62%, 64%, 66%, 68%, 70%, 72%th, 74%, 76%, 78%；

Filler 15~40%, for example, 16%, 17%, 18%, 19%, 20%, 21%, 22%th, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%th, 33%, 34%, 35%, 36%, 37%, 38%, 39%；

Adhesive 0~10%, for example, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%th, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%th, 9%, 9.5%；

Disintegrant 0~10%, for example, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%th, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%th, 9%, 9.5%；

Lubricant 0~10%, for example, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%th, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%th, 9%, 9.5%.

It is further preferred that press Balofloxacin pharmaceutical composition weight percent including following Than each component of meter：

Balofloxacin 50~70%, for example, 52%, 54%, 56%, 58%, 60%, 62%th, 64%, 66%, 68%；

Filler 20~30%, for example, 21%, 22%, 23%, 24%, 25%, 26%, 27%th, 28%, 29%；

Adhesive 2~8%, for example, 2.5%, 3%, 3.5%, 4.0%, 4.5%, 5%, 5.5%th, 6%, 6.5%, 7%, 7.5%；

Disintegrant 2~8%, for example, 2.5%, 3%, 3.5%, 4.0%, 4.5%, 5%, 5.5%th, 6%, 6.5%, 7%, 7.5%；

Lubricant 0~5%, for example, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%th, 4%, 4.5%.

Most preferably, it is including following based on Balofloxacin pharmaceutical composition percentage by weight Each component：

Balofloxacin 55~65%, for example, 56%, 57%, 58%, 59%, 60%, 61%th, 62%, 63%, 64%, 65%；

Filler 22~27%, for example, 22.5%, 23%, 23.5%, 24%, 24.5%, 25%th, 25.5%, 26%, 26.5%；

Adhesive 3~7%, for example, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%；

Disintegrant 3~7%, for example, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%；

Lubricant 1.0~4.0%, for example, 1.2%, 1.4%, 1.6%, 1.8%, 2.0%, 2.2%th, 2.4%, 2.6%, 2.8%, 3.0%, 3.2%, 3.4%, 3.6%, 3.8%.

Tried by analyzing influence and supplementary material compatibility of the different auxiliary material to formulation properties Test, with reference to the physicochemical property of Balofloxacin, with apparent shape, mixed-powder angle of repose, Tablet friability, dissolution rate are inspection target, carry out recipe determination, determine filler, Particular compound used in adhesive, disintegrant and lubricant agent.

Wherein：

The filler is Icing Sugar, dextrin, lactose, amylum pregelatinisatum, microcrystalline cellulose Element, calcium monohydrogen phosphate, mannitol, calcium carbonate, glucose, sorbierite, compressibility sugarcane One or both of sugar, white bole, ethyl cellulose；

The filler is more preferably：Icing Sugar, sorbierite, compressible sucrose, In dextrin, amylum pregelatinisatum, microcrystalline cellulose, calcium monohydrogen phosphate, mannitol and lactose One or two；

The filler is more preferably：Lactose, amylum pregelatinisatum, microcrystalline cellulose, One or both of calcium monohydrogen phosphate and mannitol；

Wherein：

Described adhesive is starch slurry, dextrin, syrup, maltose, refined honey, liquid Portugal Grape sugar, glucan, mucialga of arabic gummy, gelatine size, methylcellulose, carboxymethyl are fine Tie up plain sodium, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, hydroxyl Second cellulose, hymetellose, polyvinylpyrrolidone (PVP), pregelatinated form sediment It is powder, PVP, sodium alginate, polyethylene glycol, Magnesiumaluminumsilicate, Arabic gum, poly- One kind in ethylene glycol and carbomer；

Described adhesive is more preferably：Sodium carboxymethylcellulose, hydroxy propyl cellulose Element, PEG 8000, hydroxypropyl methyl cellulose, starch slurry, pregelatinized starch, One kind in PVP K30, gelatine size and sucrose；

Described adhesive is more preferably：PEG 8000, starch slurry, pregelatinated form sediment One kind in powder and PVP K30；

Wherein：

The disintegrant is microcrystalline cellulose, powdered cellulose, chitosan, micro mist silicon Glue, Ac-Di-Sol, PVPP, dried starch, pregelatinized starch, Sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, PVPP, Crosslinked carboxymethyl fecula sodium, guar gum, aluminium-magnesium silicate, methylcellulose, Andrea Pollack One kind in woods potassium, PVPP and sodium alginate；

The disintegrant is more preferably：Dried starch, PVPP, low substitution Hydroxypropyl cellulose, Ac-Di-Sol, PVPP and One kind in sodium carboxymethyl starch；

The disintegrant is more preferably：PVPP, low-substituted hydroxypropyl cellulose, One kind in Ac-Di-Sol and sodium carboxymethyl starch.

Wherein：

The lubricant be magnesium stearate, stearic acid, fumaric acid sodium, Macrogol 6000, Lauryl sodium sulfate, sorb acid glyceride, superfine silica gel powder, hydrogenated vegetable oil and cunning One or both of stone flour；

The lubricant is more preferably：Superfine silica gel powder, talcum powder, hydrogenated vegetable One or both of oil, lauryl sodium sulfate and magnesium stearate.

Technical scheme is used by the present invention solves above-mentioned second technical problem：

A kind of preparation method of above-mentioned Balofloxacin pharmaceutical composition, comprises the steps：

(1) a. weighs Balofloxacin and filler by formula dosage, and uses 50~100 Eye mesh screen sieves, further preferred 60~90 eye mesh screen, most preferably 70~80 mesh sieves Net；B. disintegrant is weighed by formula dosage, and is sieved using 50~100 eye mesh screens, entered One step preferably 60~90 eye mesh screens, most preferably 70~80 eye mesh screens；By in a and b Material after sieving uniformly mixes 1~20min in mixer, further preferably 3~18min, most preferably 5~15min, obtain supplementary material mixture；

(2) it is the adhesive for being formulated dosage is soluble in water and stir, bonded Liquid, the percentage that adhesive accounts for slurry gross weight in the slurry is 1~10%, is entered One step preferably 2%~8%, most preferably 3%~7%；When not including adhesive in adapted The step can be omitted；

(3) slurry in supplementary material mixture in step (1) and step (2) is put Enter to carry out in comminutor 1~10min of granulation (further preferred 1~5min, most preferably 2~3min) softwood particle is made, gained softwood particle is (further at 40~80 DEG C It is preferred that 50~70 DEG C, most preferably 55~65 DEG C) under dry 0.5~4h (further preferably 1~3.5h, most preferably 1.5~2.5h) dry particle is obtained, the dry particle is used 10~30 mesh (further preferred 14~26 eye mesh screen, most preferably 16~20 eye mesh screens) Screen cloth sieving, obtain sieve dry particle；Comminutor bag used in the step Include but be not limited to mixed at high speed comminutor or Squeezinggranulator or wave comminutor；And The step can be omitted in the case of without using respective components；

(4) sieving dry particle in step (3) is put with being formulated the lubricant of dosage In in mixer mix 3~20min (further preferred 5~15min, most preferably 8~12min), obtain hybrid particles；And using tablet press machine by the hybrid particles tabletting, Obtain label；

(5) use concentration for 2~10wt.% (further preferred 4%~8%, most preferably 5%~7%) coating solution is coated by coating equipment in sugar production line to label in step (4), Tablet medicine is obtained, wherein coating equipment in sugar production line includes but is not limited to high-efficiency coating machine or sugar-coat Machine or fluid bed；And coated preparation uses pharmaceutically acceptable auxiliary material in coating solution, The preferred water of coating solvent or ethanol.

Property based on Balofloxacin, by various pharmaceutically acceptable auxiliary materials pair The impact analysis of formulation properties and supplementary material compatibility test, it is fine from lactose, crystallite Tie up element, sodium carboxymethyl starch, PVP k30 and superfine silica gel powder, magnesium stearate conduct The auxiliary material of recipe determination, using hardness, friability and dissolution rate as inspection target, carry out Recipe determination.By to lactose, microcrystalline cellulose, sodium carboxymethyl starch, PVP K30 and superfine silica gel powder, the ratio of magnesium stearate and dosage are investigated, it is determined that formula Composition and formula ratio.Through lab scale and laboratory reappearance test, by being carried out to sample Examine, the formula composition and formula ratio of this product are verified.

Technical scheme is used by the present invention solves above-mentioned 3rd technical problem：

Above-mentioned Balofloxacin pharmaceutical composition is caused in preparation prevention and treatment by sensitive bacteria Simple form urinary tract infections, pelvic inflammation and Cervicitis pharmaceutical preparation in apply.

Compared with prior art, the advantage of the invention is that：This Balofloxacin medicine group Compound optimizes the proportioning shared by each component, and technique is simple, and yield is high, reaches 99%, It is easy to production to amplify, has completed 1,000,000 amplifications；Ifs vitro disintegration reaches in 5 minutes 85%, dissolution is rapid in vivo, and clinical onset of action is fast, effect is good.

Embodiment

Below with prior art as a comparison case and with reference to the specific embodiment of the invention to this Invention is described in detail.

Comparative example

A kind of Balofloxacin pharmaceutical composition proposed in the prior art is：

Its preparation method is：

(1) supplementary material is crossed into 100 mesh sieves respectively, takes the shallow lake that weight is 25% recipe quantity Powder, adds water, and the weight ratio of starch and water is 7:100, temperature is heated to as 75 DEG C mashing, binder is made；

(2) the starch mixing of the Balofloxacin of recipe quantity, microcrystalline cellulose and surplus is taken Uniformly, add the binder that step (1) obtains and softwood is made, it is wet to cross 20 mesh sieve series Particle, wet granular are 55 DEG C of dryings untill water content is 4% in temperature；

(3) after particle drying, 20 mesh sieve whole grains are crossed, add the stearic acid of recipe quantity Magnesium is well mixed, and Balofloxacin content is surveyed in middle product examine, and then tabletting obtains Ba Luosha Star piece.

According to above-mentioned preparation process, three crowdes of Ba Luo are prepared under same process conditions Husky star pharmaceutical composition, the performance such as institute of table 1 of this three batches of Balofloxacin pharmaceutical compositions Show.

The performance of the three batches of pharmaceutical compositions prepared under 1 same process conditions of table

	First	Second batch	3rd batch
				Hardness/KN	9.1	8.9	9.2
Friability/%	0.55	0.45	0.48
				Dissolution rate/%	97.4	96.0	97.0

Specific embodiment 1：

Wherein, filler is lactose, amylum pregelatinisatum, and adhesive is PEG 8000, Disintegrant is PVPP, and lubricant is superfine silica gel powder, talcum powder.

The preparation method of the Balofloxacin pharmaceutical composition of the present embodiment, including following step Suddenly：

(1) pretreatment of supplementary material, by the Balofloxacin in prescription, filler, disintegration Agent, lubricant 100 mesh of sieving are standby；

(2) slurry is prepared, it is by matching that adhesive is soluble in water, slurry is made, In slurry, adhesive accounts for 5.0%；

(3) dispensing, Balofloxacin, filler and disintegrant are weighed by proportioning, and put into Mixing 10min, obtains supplementary material mixture in quick mixed granulation machine；

(4) pelletize, dry and whole grain, add adhesive in supplementary material mixture, adopt 3min is granulated with mixed at high speed comminutor softwood is made, using 65 DEG C of dry 2h, do With obtaining hybrid particles after 20 eye mesh screen whole grains after the completion of dry；

(5) mix, dry particl is put into mixer mixing 12min with lubricant, obtained Hybrid particles；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, 6% coating solution is prepared with water and is coated through high-efficiency coating machine, is obtained Piece is completed to Balofloxacin.

According to above-mentioned preparation process, three crowdes of Ba Luo are prepared under same process conditions Husky star pharmaceutical composition, the performance such as institute of table 2 of this three batches of Balofloxacin pharmaceutical compositions Show.

The performance of the three batches of pharmaceutical compositions prepared under 2 same process conditions of table

Verification Project	First	Second batch	3rd batch
				Hardness/KN	10.22	10.31	10.19
Friability/%	0.19	0.21	0.23
				Dissolution rate/%	99.5	99.5	99.6

The balofloxacin tablets accelerated test data of table 3

Time/the moon	Character	30min dissolution rates/%	Relevant material/%	Content/%
					0	Show off-white color after removing film-coating	100.06	0.18	99.63
1	Show off-white color after removing film-coating	100.02	0.19	99.54
					2	Show off-white color after removing film-coating	99.76	0.21	101.15
3	Show off-white color after removing film-coating	99.00	0.23	99.65
					6	Show off-white color after removing film-coating	99.52	0.26	101.04

The specific embodiment of the invention is compared with the prior art to bar of embodiment preparation gained The dissolution rate of Lip river sand star pharmaceutical composition is contrasted, as a result referring to described in table 4.

The specific embodiment of the invention Balofloxacin of table 4 is compared with the prior art the dissolution of example Degree contrast

Contrasted by table 1 and table 2 it can be inferred that, bar prepared by the method for the present embodiment Lip river sand star pharmaceutical composition items property is stable, dissolution rapidly completely and stably, so as to Illustrate that this preparation method has preferably reappearance；Simultaneously general big production product yield 93% or so, and the yield of this method can reach 99%, be more suitable for producing greatly； In addition by 3 provable this product of table by study on the stability and the proof of clinical test, production Well, stably, clinical advantage is obvious, and adverse reaction is few for quality；Above-mentioned existing skill Balofloxacin tablets in art are the Q-roxin Tab of Korean company production, and specification is 100mg/ pieces, ground more than import original by 4 provable preparation method dissolution rates of table It hurry up, 5min dissolution rates are more than 85%；

Specific embodiment 2

The Balofloxacin pharmaceutical composition of the present embodiment presses Balofloxacin medicine including following The each component of composition weight percentages：

Preparation method：

(1) pretreatment of supplementary material, by the Balofloxacin in prescription, filler, disintegration Agent, lubricant 90 mesh of sieving are standby；

(2) 2% slurry is prepared, by proportioning by adhesive obtained slurry soluble in water；

(3) dispensing, Balofloxacin, filler and disintegrant are weighed by proportioning, and put into Mixing 1min in comminutor is waved, obtains supplementary material mixture；

(4) pelletize, dry and whole grain, add adhesive in supplementary material mixture, adopt Softwood is made with comminutor granulation 1min is waved, using 40 DEG C of dry 1h, has dried Hybrid particles are obtained after the eye mesh screen whole grains of Cheng Houyong 26；

(5) mix, dry particl is put into mixer mixing 10min with lubricant, obtained Hybrid particles；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, 7% coating solution prepared with ethanol is coated through high-efficiency coating machine, Obtain Balofloxacin and complete piece.

Performance test results are as shown in table 5.

Table 5

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	8.80	Send out YD-20 hardness testers in extremely big day
Friability %	0.83	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	90.2	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 3

Wherein, filler is lactose, and adhesive is starch, and disintegrant is that carboxymethyl is fine Plain sodium is tieed up, lubricant is superfine silica gel powder.

Preparation method：

(1) pretreatment of supplementary material, by the Balofloxacin in prescription, filler, disintegration Agent, lubricant 80 mesh of sieving are standby；

(2) 3% slurry is prepared, by proportioning by adhesive obtained slurry soluble in water；

(3) dispensing, Balofloxacin, filler and disintegrant are weighed by proportioning, and put into Mixing 3min, obtains supplementary material mixture in quick mixed granulation machine；

(4) pelletize, dry and whole grain, add adhesive in supplementary material mixture, adopt 2min is granulated with mixed at high speed comminutor softwood is made, using 50 DEG C of dry 2h, do With obtaining hybrid particles after 14 eye mesh screen whole grains after the completion of dry；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, 5% coating solution is prepared through sugar-coat pan coating with water, obtains bar Lip river sand star completes piece.Performance test results such as table 6 is as follows.

Table 6

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	9.12	Send out YD-20 hardness testers in extremely big day
Friability %	0.34	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	90.3	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 4

Wherein, filler is lactose, calcium monohydrogen phosphate, and adhesive is pregelatinized starch, Disintegrant is sodium carboxymethyl starch, and lubricant is superfine silica gel powder, lauryl sodium sulfate.

Preparation method：

(2) 5% slurry is prepared, by proportioning by adhesive obtained slurry soluble in water；

(3) dispensing, Balofloxacin, filler and disintegrant are weighed by proportioning, and put into Mixing 5min, obtains supplementary material mixture in quick mixed granulation machine；

(4) pelletize, dry and whole grain, add adhesive in supplementary material mixture, adopt 2.5min is granulated with mixed at high speed comminutor, and softwood is made, using 55 DEG C of dry 2.5h, With obtaining hybrid particles after 18 eye mesh screen whole grains after the completion of drying；

(5) mix, dry particl is put into mixer mixing 8min with lubricant, obtained Hybrid particles；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, prepares 8% coating solution through fluidized bed coating with ethanol, obtain Balofloxacin completes piece.Performance test results are as shown in table 7.

Table 7

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	9.85	Send out YD-20 hardness testers in extremely big day
Friability %	0.28	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	95.6	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 5

Wherein, filler is mannitol, and adhesive is PVP, and disintegrant takes to be low For hydroxypropyl cellulose, lubricant is superfine silica gel powder, magnesium stearate.

Preparation method：

(1) pretreatment of supplementary material, by the Balofloxacin in prescription, filler, disintegration Agent, lubricant 70 mesh of sieving are standby；

(2) 7% slurry is prepared, by proportioning by adhesive obtained slurry soluble in water；

(4) pelletize, dry and whole grain, adhesive added in supplementary material mixture, 3min is granulated using mixed at high speed comminutor softwood is made, using 60 DEG C of dry 0.5h, With obtaining hybrid particles after 30 eye mesh screen whole grains after the completion of drying；

(5) mix, dry particl is put into mixer mixing 20min with lubricant, obtained Hybrid particles；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, 4% coating solution is prepared with ethanol and is coated through high-efficiency coating machine, Obtain Balofloxacin and complete piece.

Performance test results are as shown in table 8.

Table 8

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	9.67	Send out YD-20 hardness testers in extremely big day
Friability %	0.11	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	94.5	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 6

Wherein, filler is amylum pregelatinisatum, microcrystalline cellulose, and adhesive is poly- second Glycol 8000, disintegrant are PVPP, and lubricant is talcum powder, hydrogenated vegetable Oil.

Preparation method：

(1) pretreatment of supplementary material, by the Balofloxacin in prescription, filler, disintegration Agent, lubricant 50 mesh of sieving are standby；

(2) 8% slurry is prepared, it is by matching that adhesive is soluble in water, bonding is made Liquid；

(3) dispensing, Balofloxacin, filler and disintegrant are weighed by proportioning, and put into Mixing 15min, obtains supplementary material mixture in quick mixed granulation machine；

(4) pelletize, dry and whole grain, add adhesive in supplementary material mixture, adopt 5min is granulated with mixed at high speed comminutor, and softwood is made, using 65 DEG C of dry 0.5h, With obtaining hybrid particles after 30 eye mesh screen whole grains after the completion of drying；

(5) mix, dry particl is put into mixer mixing 3min with lubricant, obtained Hybrid particles；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, 10% coating solution is prepared with water and is coated through high-efficiency coating machine, is obtained Piece is completed to Balofloxacin.

Performance test results are as shown in table 9：

Table 9

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	8.26	Send out YD-20 hardness testers in extremely big day
Friability %	0.74	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	89.5	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 7

The Balofloxacin pharmaceutical composition of the present embodiment includes the group of following percentage by weight Point：

Wherein, filler is amylum pregelatinisatum, calcium monohydrogen phosphate, and adhesive is starch, Disintegrant is sodium carboxymethylcellulose, and lubricant is talcum powder, lauryl sodium sulfate.

Preparation method：

(2) 10% slurry is prepared, it is by matching that adhesive is soluble in water, bonding is made Liquid；

(3) dispensing, Balofloxacin, filler and disintegrant are weighed by proportioning, and put into Mixing 18min, obtains supplementary material mixture in quick mixed granulation machine；

(4) pelletize, dry and whole grain, add adhesive in supplementary material mixture, adopt 10min is granulated with mixed at high speed comminutor, and softwood is made, using 70 DEG C of dry 3.5h, With obtaining hybrid particles after 16 eye mesh screen whole grains after the completion of drying；

(5) mix, dry particl is put into mixer mixing 5min with lubricant, obtained Hybrid particles；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, 2% coating solution is prepared with ethanol and is coated through high-efficiency coating machine, Obtain Balofloxacin and complete piece.

Performance test results are as shown in table 10.

Table 10

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	7.89	Send out YD-20 hardness testers in extremely big day
Friability %	0.88	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	91.9	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 8

Wherein, filler is amylum pregelatinisatum, mannitol, and lubricant is magnesium stearate.

Preparation method：

(1) pretreatment of supplementary material, by the Balofloxacin in prescription, filler, lubrication Agent 60 mesh of sieving are standby；

(2) dispensing, Balofloxacin and filler are weighed by proportioning, and put into quick mixed Mixing 20min in comminutor is closed, obtains supplementary material mixture；

(3) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(4) it is coated, 2% coating solution prepared with ethanol is coated through high-efficiency coating machine, Obtain Balofloxacin and complete piece.Performance test results are as shown in table 11.

Table 11

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	8.09	Send out YD-20 hardness testers in extremely big day
Friability %	0.80	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	90.2	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 9

The Balofloxacin pharmaceutical composition of the present embodiment includes following by Balofloxacin The each component of pharmaceutical composition percentage by weight meter：

Wherein, filler is microcrystalline cellulose, and adhesive is PVP, and disintegrant is Low-substituted hydroxypropyl cellulose, lubricant are lauryl sodium sulfate.

Preparation method：

(1) pretreatment of supplementary material, by the Balofloxacin in prescription, filler, disintegration Agent, lubricant 75 mesh of sieving are standby；

(2) dispensing, Balofloxacin, filler and disintegrant are weighed by proportioning, and put into Mixing 1min in crushing failure at high speed comminutor, obtains supplementary material mixture；

(3) pelletize, dry and whole grain, add adhesive in supplementary material mixture, adopt 1min is granulated with Squeezinggranulator, obtains hybrid particles；

(4) mix, dry particl is put into mixer mixing 10min with lubricant, obtained Hybrid particles；

(5) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(6) it is coated, 7% coating solution is prepared with water and is coated through high-efficiency coating machine, is obtained Piece is completed to Balofloxacin.Performance test results are as shown in table 12.

Table 12

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	9.98	Send out YD-20 hardness testers in extremely big day
Friability %	0.34	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	90.5	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 10

Wherein, filler is microcrystalline cellulose, mannitol, and adhesive is polyethylene glycol 8000, disintegrant is PVPP, and lubricant is hydrogenated vegetable oil, magnesium stearate.

Preparation method：

(4) pelletize, dry and whole grain, add adhesive in supplementary material mixture, adopt 2.5min is granulated with mixed at high speed comminutor, and softwood is made, using 50 DEG C of dry 4h, With obtaining hybrid particles after 10 eye mesh screen whole grains after the completion of drying；

(5) mix, dry particl is put into mixer mixing 15min with lubricant and mixed Close particle；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, is coated with the coating solution prepared through high-efficiency coating machine, obtains Ba Luo Sha Xing completes piece.Performance test results are as shown in table 13.

Table 13

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	10.03	Send out YD-20 hardness testers in extremely big day
Friability %	0.26	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	90.5	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 11

Wherein, filler is mannitol, and adhesive is starch, and disintegrant is carboxymethyl Sodium cellulosate, lubricant are lauryl sodium sulfate, magnesium stearate.

Preparation method：

(2) 7% slurry is prepared, it is by matching that adhesive is soluble in water, bonding is made Liquid；

(4) pelletize, dry and whole grain, add adhesive in supplementary material mixture, adopt 3min is granulated with mixed at high speed comminutor, and softwood is made, using 80 DEG C of dry 1.5h, With obtaining hybrid particles after 20 eye mesh screen whole grains after the completion of drying；

(5) mix, dry particl is put into mixer mixing 1min with lubricant, obtained Hybrid particles；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, 6% coating solution is prepared with ethanol and is coated through high-efficiency coating machine, Obtain Balofloxacin and complete piece.

Performance test results are as shown in table 14.

Table 14

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	10.01	Send out YD-20 hardness testers in extremely big day
Friability %	0.25	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	89.3	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 12

Wherein, filler is microcrystalline cellulose, and adhesive is pregelatinized starch, disintegration Agent is PVPP, and lubricant is superfine silica gel powder, magnesium stearate.

Preparation method：

(1) pretreatment of supplementary material, by the Balofloxacin in prescription, filler, lubrication Agent 80 mesh of sieving are standby；

(2) 8% slurry is prepared, by proportioning by adhesive obtained slurry soluble in water；

(3) dispensing, Balofloxacin and filler are weighed by proportioning, and puts quick mixing into Mixing 18min in comminutor, obtains supplementary material mixture；

(4) pelletize, dry and whole grain, adhesive added in supplementary material mixture, 10min is granulated using mixed at high speed comminutor softwood is made, using 40 DEG C of dry 3.5h, With obtaining hybrid particles after 10 eye mesh screen whole grains after the completion of drying；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, 5% coating solution prepared with ethanol is coated through high-efficiency coating machine, Obtain Balofloxacin and complete piece.Performance test results are as shown in Table 15.

Table 15

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	10.11	Send out YD-20 hardness testers in extremely big day
Friability %	0.19	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	94.8	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 13

Wherein, filler is lactose, calcium monohydrogen phosphate, and adhesive is PEG 8000, Disintegrant is low-substituted hydroxypropyl cellulose, and lubricant is talcum powder.

Preparation method：

(4) pelletize, dry and whole grain, add adhesive in supplementary material mixture, adopt 3min is granulated with mixed at high speed comminutor softwood is made, using 70 DEG C of dry 2h, do With obtaining hybrid particles after 26 eye mesh screen whole grains after the completion of dry；

(6) tabletting, by hybrid particles tabletting, Balofloxacin label is made；

(7) it is coated, is coated with the coating solution prepared through high-efficiency coating machine, obtains Ba Luo Sha Xing completes piece.Performance test results are as shown in table 16.

Table 16

Detection project	Testing result	INSTRUMENT MODEL
			Hardness/KN	10.16	Send out YD-20 hardness testers in extremely big day
Friability %	0.15	Send out FT-2000 friability instrument in extremely big day
			Dissolution rate/%	86.4	SOTAX AT 7smart digestion instruments；PE UV

Specific embodiment 14

The present embodiment is the vagina caused by balofloxacin tablets Pyrogentisinic Acid's rubber cement of embodiment 1 The experiment of the effect of cervicitis rat model.

Material：

(1) animal：SD rats, female, unpregnancy, SPF levels, body weight 200-220g.

(2) medicine and reagent：Medicine is believed in balofloxacin tablets, Kunshan forever, specification 100mg, Clinical people's dosage：Twice a day, one at a time；FUKE QIANJIN PIAN, Zhuzhou a thousand pieces of gold medicine Industry limited company；Estradiol benzoate injection；Hydrocortisone parenteral solution； Hydroxybenzene mucilage.

Method：

(1) modeling：Female rats 70 are taken, select 10 to be served only for sham-operation group at random, Residue 60 is served only for modeling.After adaptability is fed one week, rat pre-operative anxiety, abdominal cavity Inject 10% chloraldurate (300mg/KG) anesthesia, fixation of lying on the back, lower abdominal surgery Position unhairing, routine disinfection.In the bottom of midline abdominal, the vertical openings of 1cm are cut off, Ovary is found, extracts bilateral ovaries.Postoperative muscle injection penicillin prevents from infecting.2nd It rises and does vaginal smear examination, for three days on end, vagina epithelium angling is had no under microscope Cell, show that rat is in anoestrum, show that ovary has been extractd completely.Postoperative 4th It start be subcutaneously injected estradiol benzoate injection 2mg/KG and hydrogenation can injection Liquid pine 60mg/KG, it is therefore an objective to cause false estrus and general immunity hypofunction, 1 It 1 time, for three days on end, postoperative 7th day, mouse stomach pin is connect with sterilizing syringe Head, Hydroxybenzene mucilage 0.1ml is extracted, rat takes position upside down, Hydroxybenzene mucilage is injected cloudy In road uterine neck, original position stops 1~2min, prevents liquid from overflowing.1 day 1 time, totally 3 It is secondary.(dead 3 during modeling, surviving 57)

(2) it is grouped and is administered：The rat 50 of modeling is randomly selected, and is randomly divided into 5 groups, every group 10, i.e., model control group, FUKE QIANJIN PIAN group (1.48g/kg), bar The Lip river large, medium and small dosage group of sand star piece (0.007g/kg, 0.0035g/kg, 0.0017g/kg), Balofloxacin tablets last dissolve in deionized water of pulverizing is administered, administration frequency 1 It 1 time, administered volume 10ml/kg, sham-operation group and model control group gavage are isometric Deionized water, successive administration 8 days.

(3) Indexs measure：

Leukocyte count：The 2nd day of last dose, each group Rat Fast can't help water 12h, Weigh, 10% chloraldurate 300mg/kg intraperitoneal injection of anesthesia, abdominal aortic blood, Leukocyte count is determined with microscope count method.

Vagina uterine neck organ index：Take and organize to weigh at vagina to uterus subangle, calculate Vagina and uterine neck organ index, organ index=organ weights/body weight × 100.

As a result：

Balofloxacin tablets are influenceed referring to table 17 on vagina cervicitis rat model leucocyte.

Table 17

Balofloxacin tablets are to vagina cervicitis rat model vagina and uterine neck organ index Influence referring to table 18.

Table 18

Leukocyte count：Compared with sham-operation group, the rise of model group leucocyte, Ba Luosha The large, medium and small dosage group of star piece and FUKE QIANJIN PIAN group can significantly reduce total white blood cells, Balofloxacin tablets win especially；

Vagina and uterine neck organ index：Compared with sham-operation group, model group vagina uterine neck Organ index increases, the large, medium and small dosage group of balofloxacin tablets and FUKE QIANJIN PIAN group The reduction of rat vagina uterine neck organ index can be made, balofloxacin tablets win especially.

Summarize：The large, medium and small dosage of balofloxacin tablets can produce to vagina cervicitis Curative effect, and curative effect is better than FUKE QIANJIN PIAN.

Specific embodiment 15

The present embodiment is chronic caused by balofloxacin tablets Pyrogentisinic Acid's rubber cement of embodiment 1 The experiment of the effect of pelvic infecton rat model.

Material：

(1) animal：SD rats, female, unpregnancy, SPF levels, body weight 200-220g.

(2) medicine and reagent：Medicine is believed in balofloxacin tablets, Kunshan forever, specification 100mg, Clinical people's dosage：Twice a day, one at a time；GUIZHI FULING JIAONANG, Jiangsu Kang Yuan Medicine company limited company；Hydroxybenzene mucilage.

Method：

(1) modeling：Female rats 60 are taken to be served only for modeling.Modeling method refers to《Doctor Medicine experimental animal model-making and application》, Animal Anesthesia, belly routine disinfection, under Median abdominal incision about 2cm, exposure uterus, with No. 4 syringe needles respectively in uterus crotch Careful inserting needle, Hydroxybenzene mucilage 0.05mL being slowly injected into ovary direction, injection finishes, Abdomen, sterile surgical area are closed in layering.During modeling and after modeling 10 days without rats death, After modeling 10 days, all own all healeds of rat abdomen wound, randomly select 2 big Mouse, to be dissected after anesthesia, gross examination of skeletal muscle is shown in uterine tissue and other tissue adhesions of pelvic cavity, Uterus swelling, hyperemia are obvious, wherein 1 rat uterus chamber upper end hydrops.Win son Palace tissue does pathological section, and light Microscopic observation endometrial epithelium and glandular epithelium increase It is raw, a large amount of lymphocytic infiltrations, placenta percreta congestion and edema, as a result hints model preparation Success.

(2) it is grouped and is administered：Remaining 48 modeling rats are randomly divided into:Normal group, Model group, the large, medium and small dosage group of balofloxacin tablets (0.007g/kg, 0.0035g/kg, 0.0017g/kg), positive controls GUIZHI FULING JIAONANG (0.326g/kg).By Ba Luosha Star slice lapping is administered into dissolving in deionized water after powder, administration frequency 1 day 1 time, Administered volume 10ml/kg, normal group and the isometric deionized water of model control group gavage, Successive administration 20 days.

(3) draw materials：After last dose 1h, 10% chloral hydrate anesthesia, heart takes Blood 5mL is placed in the test tube for being not added with anti-coagulants, and separation serum is standby；Take big after blood Mouse skin of abdomen routine disinfection, exposure uterus.Each group rats with left uterus is put into 10% It is fixed in neutral formalin solution, FFPE, section, Hematoxylin-eosin (HE) Dyeing, carry out pathological observation；Right uterine, weigh, by mass volume ratio plus physiology salt Water is prepared into 20% tissue homogenate, carries out enzyme linked immunosorbent detection.

(4) Indexs measure：

Endometrial Pathologic morphological scoring：Using Endometrial Diseases as observation emphasis, Lesion degree standards of grading are:0 point, endometrium can have without obvious cell infiltration Slight epithelial hyperplasia, without obvious epithelial cell regression, no inner membrance congestion and edema；3 Point, cell infiltration that endometrium is slight, light, moderate epithelial hyperplasia, minority Epithelial cell regression, the slight congestion and edema of inner membrance；6 points, endometrium moderate inflammatory cell Infiltration, light, moderate epithelial hyperplasia, moderate epithelial cell regression, inner membrance are slight Congestion and edema；9 points, endometrium severe cell infiltration, light, moderate epithelial cell Hyperplasia, moderate epithelial cell regression, inner membrance moderate congestion and edema；12 points, intrauterine Film severe cell infiltration, severe epithelial hyperplasia, severe epithelial cell regression, Inner membrance severe congestion and edema.

Serum cytokines TNF-α, IL-2 measure：The μ L of test serum 100 are added Enter in advance with anti-rat TNF-α, on the coated ELISA Plate of IL-2 monoclonal antibodies； Reaction plate is fully mixed to rearmounted 37 DEG C of incubator 120min, makes reference substance, treat test sample Antigen in product is fully combined with monoclonal antibody；Reaction plate is fully washed 4~6 with cleaning solution It is secondary, to filter paper on print it is dry；Biotinylated primary antibody (TNF-α/IL-2) is added in per hole The μ L of working solution 50, put 37 DEG C of incubator 60min；Board-washing；Add horseradish peroxidase per hole The μ L of Streptavidin antibody working solution 100 of enzyme mark, 37 DEG C of temperature are put by reaction plate Case 60min, enzyme labelled antibody working solution is set to be combined into compound with biotinylation primary antibody； Board-washing；The μ L of OPD (o-phenylenediamine) substrates working solution 100 are added per hole, put 37 DEG C secretly Place's reaction 5min；100 μ L terminate liquids (2mol/L sulfuric acid) are added per hole；In enzyme Mark and survey each hole absorbance (A) on instrument at 492nm.With curve expert1.3 softwares, With the A of reference substance 1000,500,250,125,62,31,16,0pgmL/L Standard curve is made, TNF-α is obtained according to sample A on the graph, IL-2's Content.

Uterus ICAM-1 assays：The μ L of uterus homogenate 100 to be measured are added to pre- First with the anti-coated ELISA Plate of rat ICAM-1 monoclonal antibodies；By reaction plate Rearmounted 37 DEG C of incubator 120min are fully mixed, are made anti-in reference substance, testing sample Original is fully combined with monoclonal antibody；Reaction plate is fully washed 4~6 times with cleaning solution, to filter Printed on paper dry；The biotinylated μ L of primary antibody ICAM-1 working solutions 50 are added in per hole, Put 37 DEG C of incubator 60min；Board-washing；Add horseradish peroxidase-labeled per hole The μ L of Streptavidin antibody working solution 100, reaction plate is put into 37 DEG C of incubator 60min； Board-washing；The μ L of OPD (o-phenylenediamine) substrates working solution 100 are added per hole, put 37 DEG C secretly Place's reaction 10min；100 μ L terminate liquids (2mol/L sulfuric acid) are added per hole；In enzyme Mark and survey each hole light absorption value on instrument at 492nm.With Curveexpert1.3 softwares, with The A values of reference substance 1000,500,250,125,62,31,16,0ng/L are done Go out standard curve, obtain ICAM-1 content on the graph according to sample A.

As a result：

Each group rat endometrium lesion pathological score comparative result ginseng is shown in Table 19.

Table 19

Each group rat blood serum cytokine TNF-α, IL-2 comparative result are referring to table Shown in 20.

Table 20

Each group rat uterus ICAM-1 comparative result ginseng is shown in Table 21.

Table 21

Histological scores：The classification of each group lesion degree, appraisal result show Balofloxacin Piece, GUIZHI FULING JIAONANG can effectively improve chronic pelvic inflammatory disease rat endometrium tissue shape The pathological state of state, balofloxacin tablets win especially；

Serum cytokines TNF-α and IL-2：Compared with normal rats, model group Rat blood serum IL-2 contents substantially reduce, and TNF-α substantially increases；Through balofloxacin tablets, After Guizhi Fuling Capsule " in Treating, rat blood serum IL-2 substantially increases compared with model group, TNF-α substantially reduces, more preferable using the effect of balofloxacin tablets；

Chronic pelvic inflammatory disease rat uterus ICAM-1 contents：Model group rats uterus ICAM-1 contents are apparently higher than normal group；Compared with model group, balofloxacin tablets and osmanthus Branch Indian buead capsule rat uterus ICAM-1 contents substantially reduce.

Summarize：The large, medium and small dosage of balofloxacin tablets can produce to chronic pelvic inflammatory disease Curative effect, and curative effect is better than GUIZHI FULING JIAONANG.

It the foregoing is only the preferred embodiments of the present invention.It should be pointed out that In the case of not departing from the principle of the invention, some improvement and modification can be also made, are regarded For protection scope of the present invention.

Claims

A kind of 1. Balofloxacin pharmaceutical composition, it is characterised in that：Including it is following by bar The each component of Lip river sand star pharmaceutical composition percentage by weight meter：
2. Balofloxacin pharmaceutical composition according to claim 1, its feature exist In：Including following each components based on Balofloxacin pharmaceutical composition percentage by weight：
3. Balofloxacin pharmaceutical composition according to claim 1, its feature exist In：Including following each components based on Balofloxacin pharmaceutical composition percentage by weight：
4. Balofloxacin pharmaceutical composition according to claim 3, its feature exist In：The filler is Icing Sugar, dextrin, lactose, amylum pregelatinisatum, microcrystalline cellulose Element, calcium monohydrogen phosphate, mannitol, calcium carbonate, glucose, sorbierite, compressibility sugarcane One or both of sugar, white bole, ethyl cellulose；Described adhesive is starch Slurry, dextrin, syrup, maltose, refined honey, liquid glucose, glucan, Arab Rubber cement, gelatine size, methylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, Hydroxypropyl methyl cellulose, ethyl cellulose, hyetellose, hymetellose, Polyvinylpyrrolidone, pregelatinized starch, PVP, sodium alginate, polyethylene glycol, One kind in Magnesiumaluminumsilicate, Arabic gum, polyethylene glycol and carbomer；The disintegration Agent is microcrystalline cellulose, powdered cellulose, chitosan, superfine silica gel powder, crosslinking carboxylic first Base sodium cellulosate, PVPP, dried starch, pregelatinized starch, CMS Sodium, low-substituted hydroxypropyl cellulose, PVPP, cross-linked carboxymethyl Sodium starch, guar gum, aluminium-magnesium silicate, methylcellulose, polacrilin potassium, crosslinking One kind in PVP and sodium alginate；The lubricant be magnesium stearate, stearic acid, Fumaric acid sodium, Macrogol 6000, lauryl sodium sulfate, sorb acid glyceride, One or both of superfine silica gel powder, hydrogenated vegetable oil and talcum powder.
5. Balofloxacin pharmaceutical composition according to claim 4, its feature exist In：The filler is Icing Sugar, sorbierite, compressible sucrose, dextrin, compressibility One or both of starch, microcrystalline cellulose, calcium monohydrogen phosphate, mannitol and lactose； Described adhesive be sodium carboxymethylcellulose, hydroxypropyl cellulose, PEG 8000, Hydroxypropyl methyl cellulose, starch slurry, pregelatinized starch, PVP K30, gelatin One kind in slurry and sucrose；The disintegrant is dried starch, PVPP, low taken For hydroxypropyl cellulose, Ac-Di-Sol, PVPP With one kind in sodium carboxymethyl starch；The lubricant be superfine silica gel powder, talcum powder, One or both of hydrogenated vegetable oil, lauryl sodium sulfate and magnesium stearate.
6. Balofloxacin pharmaceutical composition according to claim 5, its feature exist In：The filler is lactose, amylum pregelatinisatum, microcrystalline cellulose, calcium monohydrogen phosphate One or both of with mannitol；Described adhesive is PEG 8000, starch One kind in slurry, pregelatinized starch and PVP K30；The disintegrant is poly- for crosslinking Ketone, low-substituted hydroxypropyl cellulose, Ac-Di-Sol and carboxymethyl is tieed up to form sediment One kind in powder sodium.
A kind of 7. Balofloxacin medicine described in any claim in claim 1 to 6 The preparation method of composition, it is characterised in that：Comprise the steps：

(1) a. weighs Balofloxacin and filler by formula dosage, and uses 50~100 Eye mesh screen sieves；B. disintegrant is weighed by formula dosage, and uses 50~100 eye mesh screens Sieving；Material after being sieved in a and b is uniformly mixed into 1~20min in mixer, Obtain supplementary material mixture；

(2) it is the adhesive for being formulated dosage is soluble in water and stir, bonded Liquid, the percentage that adhesive accounts for slurry gross weight in the slurry are 1~10%；

(3) slurry in supplementary material mixture in step (1) and step (2) is put Enter to carry out 1~10min of granulation in comminutor and softwood particle is made, by gained softwood particle 0.5~4h is dried at 40~80 DEG C and obtains dry particle, the dry particle is used The screen cloth sieving of 10~30 mesh, obtains dry particle of sieving；

(4) sieving dry particle in step (3) is put with being formulated the lubricant of dosage In mixing 3~20min in mixer, hybrid particles are obtained；And should using tablet press machine Hybrid particles tabletting, obtains label；

(5) use concentration for 2~10wt.% coating solution by coating equipment in sugar production line to step (4) Middle label is coated, and obtains tablet medicine.
8. the preparation method of Balofloxacin pharmaceutical composition according to claim 7, It is characterized in that：Screen cloth employed in step (1) is 60~90 mesh, and is mixed Time is 3~18min；Adhesive accounts for slurry gross weight in slurry in step (2) Percentage be 2~8%；Granulation time is 1~5min in step (3), drying temperature For 50~70 DEG C, drying time is 1~3.5h, and the screen cloth of dry particle sieving is 14~26 Mesh；Incorporation time is 5~15min in step (4)；Coating solution in step (5) Concentration is 4~8wt.%.
9. the preparation method of Balofloxacin pharmaceutical composition according to claim 8, It is characterized in that：Screen cloth employed in step (1) is 70~80 mesh, and during mixing Between be 5~15min；Adhesive accounts for slurry gross weight in slurry in step (2) Percentage is 3~7%；Granulation time is 2~3min in step (3), and drying temperature is 55~65 DEG C, drying time is 1.5~2.5h, and the screen cloth of dry particle sieving is 16~20 Mesh；Incorporation time is 8~12min in step (4)；Coating solution in step (5) Concentration is 5~7wt.%.
A kind of 10. Balofloxacin medicine in claim 1~6 described in any claim The application of compositions, it is characterised in that：Prevention and treatment are prepared by sensitive bacteria to be caused Simple form urinary tract infections, the pharmaceutical preparation of pelvic inflammation and Cervicitis.