CN106432271A - Pharmaceutical ceftibuten crystal compound for treating surgical infection - Google Patents
Pharmaceutical ceftibuten crystal compound for treating surgical infection Download PDFInfo
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- CN106432271A CN106432271A CN201610837277.9A CN201610837277A CN106432271A CN 106432271 A CN106432271 A CN 106432271A CN 201610837277 A CN201610837277 A CN 201610837277A CN 106432271 A CN106432271 A CN 106432271A
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- ceftibuten
- crystal compound
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/22—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with radicals containing only hydrogen and carbon atoms, attached in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicine, and discloses a pharmaceutical ceftibuten crystal compound for treating surgical infection. The structural formula of the ceftibuten crystal compound is shown in formula (I); and based on determination of the crystal compound through a powder X-ray diffraction determination method, the X-ray powder diffraction spectrum represented by a diffraction angle of 2theta +/- 0.2 degrees is shown in figure 1. The crystal compound is high in purity, low in polymer content, favorable in stability, less prone to moisture absorption and favorable in flowability; and the solubility is greatly improved. Formula (I) is shown in the specification.
Description
Technical field
The invention belongs to pharmaceutical technology field is and in particular to a kind of medicine ceftibuten crystal treating Postoperative infection
Compound.
Background technology
Ceftibuten (Ceftibuten) is broad-spectrum cephalosporin to be administered orally by the third generation that Yan Yeyi company of Japan is developed, right
Most of gram negative bacilli and some positive coccus have stronger antibacterial action, to plasmid-mediated beta-lactamase height
Stable, and there is post antibiotic effect；There is has a broad antifungal spectrum, the features such as antibacterial activity is strong, bioavailability is high, for treatment by
The various infection that sensitive strain causes, including upper respiratory tract infection, lower respiratory infection, the urinary system that oozes infection, enteritis and gastrointestinal
Inflammation etc..
The chemical name of ceftibuten be (+)-(6R, 7R) -7 β-[(Z) -2- (2- amino -4- thiazole) -4- carboxyl -2-
(Z)-crotonamide] -8- oxygen -5- sulfur -1- nitrogen bicyclic [4.2.0] oct-2-ene -2- carboxylic acid two water thing, structural formula such as formula I institute
Show：
Formula（）.
Beta-Lactam antibiotic, such as penicillin medicine and Cephalosporins, due to the less stable of parent nucleus, hold
Easily reset, decompose and polyreaction, the polymer product being formed and anaphylactic shock have close relationship.In penicillin
Averagely in 21.44 μ g/g, anaphylaxiss incidence rate is 0.2% to polymeric impurities；Polymeric impurities are averagely in 51.24 μ g/g
When, anaphylaxiss incidence rate is 0.43%；During polymeric impurities average out to 76.7 μ g/g, allergy rate is 0.74%.Cephalosporin
Though anaphylaxiss are so serious not as good as penicillin, when polymer is high, human allergy equally can be caused to react.
Ceftibuten chance light, heat, water, oxidation etc. are unstable, are also easy to produce catabolite, particularly suffer from the situation of high temperature
Under, tending to occur degraded and polyreaction, generating ceftibuten dimer, trimer and polymer etc. polymer, thus leading
Active constituents of medicine content is caused to reduce, color and luster is strengthened, polymeric impurities content raises.In addition, expired ceftibuten antibiotic,
Because the resting period is long, so that active constituents of medicine content is reduced, darken, polymer content raises.Further, exist
In some cases, because controlling of production process is improper, obtained ceftibuten dihydrate, ceftibuten dimer, trimerization
Thing and polymer etc. polymer content is especially high.And polymer content high when, easily make human body produce anaphylaxiss.So for
The high ceftibuten dihydrate of this kind of polymeric impurities content or ceftibuten pharmaceutical preparation are it is necessary to carry out pure further
Change, ceftibuten dihydrochloride dihydrate crystal that obtain high-quality, that purity is high.
Additionally, the poorly water-soluble of ceftibuten, mobility are bad, there is hygroscopicity etc. to preparation preparation bring tired
Difficulty, the capsule of its preparation mostly has that dissolution is low, and stability is bad, the defect such as polymer content height.
US4812561 discloses a kind of crystal hydrate of oral cephalosporin and combinations thereof, its disclosed crystallization
Hydrate is dihydrate, trihydrate or its mixture, and the preparation method of this crystalline hydrate is：By material dissolution in sour water
In solution, the pH making solution is in about room temperature（Specifically at 0-70 DEG C）Rise（Specifically rise to pH1.5-5.0）To separate crystallization.Must
When wanting, stirring mixture makes crystallization complete.Isolate wet crystallization, under room temperature and about atmospheric pressure, be not less than in relative humidity
It is dried in 15% noble gases.The crystalline hydrate that the method is obtained has the stability of height, and accelerated test confirms,
After one month, it remains to keep 97.8% efficiency.Present invention also offers a kind of compositionss of energy stable for extended periods of time, find
Sealing by this hydrate loading snap fit capsule and with gelatin band can make its pole not easy to change and inactivate.The preparation of capsule of the present invention
Specific as follows：By the hydrate of pharmacologically effective dose and additive（As filler, lubricant）Mutually mix, be then charged into capsule,
The periphery of capsule lid and the whole junction of body coats aqueous gelatin solution, is dried and forms gelatin band.Snap fit capsule can be common
Commodity capsule, does not have the restriction of special size and color, can contain fuel and/or pigment.But, applicant is through substantial amounts of
Experimental study confirms, the impurity content of the crystalline hydrate of gained of the present invention, especially polymer content are still very high, its flowing
Property, dissolubility also need to be improved.Although prepared capsule purity and stability are preferably, its dissolution, polymeric impurities
Content is unsatisfactory.
Preparation method the method that CN105153198A discloses a kind of ceftibuten is a kind of new to prepare ceftibuten
Method, its high income, purity is high, easy and simple to handle, is the production technology of a green cleaning, is suitable for the industry of certain scale
Metaplasia is produced.HPLC purity 98.5%-99.2%, its diffraction numerical value is close with US4812561 after measured, gained crystalline hydrate miscellaneous
Matter content, especially polymer content are high, and its mobility, dissolubility are also poor.
CN104546862A discloses a kind of ceftibuten pharmaceutical composition and preparation method thereof, and wherein capsule is by cephalo
Cloth alkene, amylum pregelatinisatum, Microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, micropowder silica gel and Pulvis Talci are prepared through specific
Method is made.The capsule that applicant prepares to it has carried out dissolution, defects inspecting and stability test, finds its dissolution
Difference, impurity content is high, and stability is also very poor.
EP3031450A1 discloses a kind of ceftibuten capsule, it comprises binding agent, disintegrating agent, lubricant, fluidizer
Agent, prescription disclosed in embodiment is two water ceftibutens, magnesium stearate, Microcrystalline Cellulose, silica sol, hydroxyacetic acid form sediment
Powder sodium, by controlling the particle diameter of two water ceftibutens, solves the dissolution leading to preparation due to ceftibuten low aqueous solubility not
Good, a difficult problem for impact drug absorption, ceftibuten preparation newly developed is easy to and rapid dispersion in vivo, have high absorption and
Bioavailability.The capsule that applicant prepares to it has carried out defects inspecting and stability test, finds that its impurity content is high, surely
Qualitative also poor, dissolution needs to be improved further.
WO2013151518A1 discloses and a kind of comprises at least two different compositionss with high water solubility pH agent
Ceftibuten capsule preparations, described preparation comprises except at least one pharmaceutically acceptable excipient and tablet composition.Can
Disintegrating agent, fluidizer, lubricant and bonding can be comprised with excipient pharmaceutically acceptable used in the preparation of the present invention
Agent, the capsule dissolution that it is obtained is higher, but finds that its impurity, polymer content are higher through test, and less stable.
The present inventor, with existing ceftibuten crude product as raw material, through lot of experiments, has been obtained one kind and has been totally different from now
There is technology（As US4812561, CN105153198A, commercially available prod etc.）Novel crystal forms ceftibuten crystalline compounds, and
By test, surprisingly find that this crystalline compounds purity is high, polymer content is low, good stability, and is difficult moisture absorption, mobility
Good, substantially increase its dissolubility.Not only purity is high, impurity content is low for the pharmaceutical composition made using this crystalline compounds,
Clarity is good, and can guarantee that subpackage efficiency in production, content uniformity are little, and adverse reaction rate substantially reduces, stability
More preferably.
Content of the invention
It is an object of the invention to provide a kind of medicine ceftibuten crystalline compounds treating Postoperative infection, this crystalline substance
Not only purity is high for body compound, and polymer content is low, good stability, and it is difficult moisture absorption, and mobility, dissolubility etc. are substantially excellent
In prior art.
For realizing the purpose of the present invention, the present invention adopts the following technical scheme that：
A kind of medicine ceftibuten crystalline compounds treating Postoperative infection, the knot of described ceftibuten crystalline compounds
As shown in formula I, this crystalline compounds is measured structure formula with powder X-ray diffraction algoscopy, the X being represented with the 2 θ ± 0.2 ° angles of diffraction
Ray powder diffraction as shown in figure 1,
Formula（）.
The present invention also provides a kind of preparation side of the medicine ceftibuten crystalline compounds of above-mentioned treatment Postoperative infection
Method, the method comprises the steps：
Take ceftibuten crude drug, in the methanol of addition uniform temperature, the mixed solvent A of dimethylformamide, obtain solution；So
Apply stationary magnetic field in the horizontal direction of the liquid level of resulting solution afterwards, and to Deca in solution under conditions of this stationary magnetic field
Acetone, ethyl acetate, the mixed solvent B of ether；After being added dropwise to complete, stand 3-5 hour, filter, filter cake washing with alcohol, vacuum
2-4 hour is dried, obtains described ceftibuten crystalline compounds.
In the present invention, described ceftibuten crude drug can be using the ceftibuten disclosed in the method for prior art
The ceftibuten for preparing of synthetic method or commercially available ceftibuten crude drug.
In above-mentioned preparation method, wherein, described uniform temperature is 15-25 DEG C.Described mixed solvent A volume（ml）For cephalo
6-8 times of cloth alkene crude drug weight (g), methanol and dimethylformamide volume ratio are 1:2.5.Described magnetic field intensity is 0.8T-
1.5T.Described mixed solvent B volume（ml）For 8-10 times of ceftibuten crude drug weight (g), acetone, ethyl acetate and ether
Volume ratio is 2:3:5.
The present invention also provides a kind of ceftibuten pharmaceutical composition, and described pharmaceutical composition is carried containing the present invention
For ceftibuten crystalline compounds or preparation method of the present invention be obtained ceftibuten crystalline compounds.
The consisting of of described ceftibuten pharmaceutical composition：Ceftibuten 1 weight portion, arginine 0.01-0.03 weight
Part.
The consisting of of described ceftibuten pharmaceutical composition：Ceftibuten 1 weight portion, arginine 0.02 weight portion.
Described ceftibuten pharmaceutical composition is prepared from by following preparation method：
（1）Weigh ceftibuten crystal and arginine in proportion, be sufficiently mixed；
（2）Subpackage to sterilize after cillin bottle in and jump a queue.
Compared with prior art, the invention has the advantages that：
（1）Not only purity is high for ceftibuten crystalline compounds provided by the present invention, and polymer content is low, good stability, and
It is difficult moisture absorption, and mobility, dissolubility etc. are substantially better than prior art；
（2）The preparation method process is simple of ceftibuten provided by the present invention, high income, repeatability is strong, is suitable for industrialization
Produce；
（3）Not only purity is high for pharmaceutical composition containing this ceftibuten crystalline compounds provided by the present invention, impurity content
Low, clarity is good, and can guarantee that subpackage efficiency in production, content uniformity are little, and adverse reaction rate substantially reduces, stable
Property is more preferable.
Brief description
Fig. 1 is the X-ray powder diffraction figure of the ceftibuten crystalline compounds of the present invention.
Fig. 2 is the heat analysis collection of illustrative plates of the ceftibuten crystalline compounds of the present invention.
Specific embodiment
With embodiment, technical scheme is described in detail below, it will help the technical side to the present invention
The advantage of case, effect have and further understand, embodiment does not limit protection scope of the present invention, protection scope of the present invention by
Claim is determining.
The preparation of embodiment 1 ceftibuten crystalline compounds
Take ceftibuten crude drug, the volume adding 15 DEG C is the methanol of 6 times of ceftibuten weight, the mixing of dimethylformamide
In solvent orange 2 A, methanol and dimethylformamide volume ratio are 1:2.5, obtain solution；Then in the level side of the liquid level of resulting solution
Upwards apply magnetic field intensity be 0.8T stationary magnetic field, and under conditions of this stationary magnetic field to Deca volume in solution be cephalo
8 times of acetone of cloth alkene weight, ethyl acetate, the mixed solvent of ether, the volume ratio of acetone, ethyl acetate and ether is 2:3:5；Drip
Plus after the completion of, stand 3-5 hour, filter, filter cake washing with alcohol, be vacuum dried 2-4 hour, obtain described ceftibuten brilliant
Body compound.
Measured with powder X-ray diffraction algoscopy（The same US4812561 of assay method）, represented with the 2 θ ± 0.2 ° angles of diffraction
X-ray powder diffraction collection（Fig. 1）5.0 °, 7.2 °, 10.0 °, 12.1 °, 14.7 °, 18.2 °, 21.5 °, 22.3 °, 23.6 °,
25.0 °, 27.1 °, 28.4 °, 28.7 °, 30.5 °, show characteristic diffraction peak at 31.2 °.
Measuring moisture using Ka Shi aquametry is 8.08wt%, substantially identical with theoretical value.
Measured using thermogravimetric analysiss, result is as shown in Fig. 2 crystal water content is 8.07wt%, substantially identical with theoretical value.
The preparation of embodiment 2 ceftibuten crystalline compounds
Take ceftibuten crude drug, the volume adding 20 DEG C is the methanol of 7 times of ceftibuten weight, the mixing of dimethylformamide
In solvent orange 2 A, methanol and dimethylformamide volume ratio are 1:2.5, obtain solution；Then in the level side of the liquid level of resulting solution
Upwards apply magnetic field intensity be 1.2T stationary magnetic field, and under conditions of this stationary magnetic field to Deca volume in solution be cephalo
9 times of acetone of cloth alkene weight, ethyl acetate, the mixed solvent of ether, the volume ratio of acetone, ethyl acetate and ether is 2:3:5；Drip
Plus after the completion of, stand 3-5 hour, filter, filter cake washing with alcohol, be vacuum dried 2-4 hour, obtain described ceftibuten brilliant
Body compound.
Measured with powder X-ray diffraction algoscopy, same with the X-ray powder diffraction collection that the 2 θ ± 0.2 ° angles of diffraction represent
Embodiment 1.
The preparation of embodiment 3 ceftibuten crystalline compounds
Take ceftibuten crude drug, the volume adding 25 DEG C is the methanol of 8 times of ceftibuten weight, the mixing of dimethylformamide
In solvent orange 2 A, methanol and dimethylformamide volume ratio are 1:2.5, obtain solution；Then in the level side of the liquid level of resulting solution
Upwards apply magnetic field intensity be 1.5T stationary magnetic field, and under conditions of this stationary magnetic field to Deca volume in solution be cephalo
10 times of acetone of cloth alkene weight, ethyl acetate, the mixed solvent of ether, the volume ratio of acetone, ethyl acetate and ether is 2:3:5；
After being added dropwise to complete, stand 3-5 hour, filter, filter cake washing with alcohol, be vacuum dried 2-4 hour, obtain described ceftibuten
Crystalline compounds.
Measured with powder X-ray diffraction algoscopy, same with the X-ray powder diffraction collection that the 2 θ ± 0.2 ° angles of diffraction represent
Embodiment 1.
The preparation of embodiment 4 ceftibuten crystalline compounds
Take ceftibuten crude drug, the volume adding 15 DEG C is the methanol of 7 times of ceftibuten weight, the mixing of dimethylformamide
In solvent orange 2 A, methanol and dimethylformamide volume ratio are 1:2.5, obtain solution；Then in the level side of the liquid level of resulting solution
Upwards apply magnetic field intensity be, the stationary magnetic field of 1.2T, and under conditions of this stationary magnetic field to Deca volume in solution be head
Spore 10 times of acetone of cloth alkene weight, ethyl acetate, the mixed solvent of ether, the volume ratio of acetone, ethyl acetate and ether is 2:3:
5；After being added dropwise to complete, stand 3-5 hour, filter, filter cake washing with alcohol, be vacuum dried 2-4 hour, obtain described cephalo cloth
Alkene crystalline compounds.
Measured with powder X-ray diffraction algoscopy, same with the X-ray powder diffraction collection that the 2 θ ± 0.2 ° angles of diffraction represent
Embodiment 1.
The preparation of embodiment 5 ceftibuten crystalline compounds
Take ceftibuten crude drug, the volume adding 25 DEG C is the methanol of 6 times of ceftibuten weight, the mixing of dimethylformamide
In solvent orange 2 A, methanol and dimethylformamide volume ratio are 1:2.5, obtain solution；Then in the level side of the liquid level of resulting solution
Upwards apply magnetic field intensity be 0.8T stationary magnetic field, and under conditions of this stationary magnetic field to Deca volume in solution be cephalo
9 times of acetone of cloth alkene weight, ethyl acetate, the mixed solvent of ether, the volume ratio of acetone, ethyl acetate and ether is 2:3:5；Drip
Plus after the completion of, stand 3-5 hour, filter, filter cake washing with alcohol, be vacuum dried 2-4 hour, obtain described ceftibuten brilliant
Body compound.
Measured with powder X-ray diffraction algoscopy, same with the X-ray powder diffraction collection that the 2 θ ± 0.2 ° angles of diffraction represent
Embodiment 1.
Example of formulations 1：The preparation of ceftibuten pharmaceutical composition：
Consist of：Ceftibuten crystal 1 weight portion of the present invention, arginine 0.01 weight portion.
Preparation method is：
（1）Weigh ceftibuten crystal and arginine in proportion, be sufficiently mixed；
（2）Subpackage to sterilize after cillin bottle in and jump a queue.
Example of formulations 2：The preparation of ceftibuten pharmaceutical composition：
Consist of：Ceftibuten crystal 1 weight portion of the present invention, arginine 0.02 weight portion.
Preparation method is：
（1）Weigh ceftibuten crystal and arginine in proportion, be sufficiently mixed；
（2）Subpackage to sterilize after cillin bottle in and jump a queue.
Example of formulations 3：The preparation of ceftibuten pharmaceutical composition：
Consist of：Ceftibuten crystal 1 weight portion of the present invention, arginine 0.03 weight portion.
Preparation method is：
（1）Weigh ceftibuten crystal and arginine in proportion, be sufficiently mixed；
（2）Subpackage to sterilize after cillin bottle in and jump a queue.
Trial target 1：Ceftibuten crystalline compounds prepared by the embodiment of the present invention 1；
Trial target 2：Ceftibuten crystalline compounds prepared by the embodiment of the present invention 4；
Reference substance 1：Method according to CN105153198A embodiment 1 is obtained ceftibuten crystalline compounds；
Reference substance 2：Method according to US4812561 example 2 is obtained ceftibuten crystalline compounds.
Experimental example 1：Fluidity test
This experimental example evaluates the mobility of sample by the angle of repose of determination sample, and concrete grammar is as follows：Take sample particle, from
Flow in fixing little funnel in the surface plate of circle, until obtaining highest cone, measure cone height H and radius R,
Calculate α angle of repose by tan α=H/R, the results are shown in Table 1, angle of repose is bigger, mobility is poorer.
Table 1 fluidity test result
As known from Table 1, compared with ceftibuten of the prior art, the ceftibuten compound flow prepared by the present invention shows
Write and improve, be conducive to the preparation of preparation, dissolution, the raising of bioavailability.
Experimental example 2：Dissolubility test
Add appropriate distilled water in the low capacity bottle with constant temperature jacket, add ceftibuten at 25 DEG C to not re-dissolved
Till, start magnetic stirrer, continuously stirred under constant temperature, system is in the state of two-phase coexistent all the time in experimentation, 70
In the liquid phase of system after minute, the concentration of ceftibuten is the dissolubility at a temperature of this.It is sampled after 2 hours analyzing, take
The close meansigma methodss of adjacent two times result as measured value of experiment, before sampling, in order that solid-liquid is sufficiently separated, stop stirring after,
Not molten ceftibuten is deposited to the bottom of low capacity bottle, extracts a small amount of upper clear supernate with syringe, with 0.45 micron of filter
Filter, take sample from filtrate, measure the content of ceftibuten by HPLC（Concentration（mg/ml））.The results are shown in Table 2.
Under table 2 room temperature, ceftibuten crystal compound of the present invention and the water solublity of prior art crystal formation contrast
From table 2 it can be seen that the water solublity of ceftibuten crystal compound of the present invention is compared with prior art, has and significantly carry
High.
Experimental example 3：Wettability test
Each sample opening is put in clean culture dish, spreads out into≤thick the thin layer of 5mm, each two parts, be respectively put into constant humidity hermetic container
In, place 10 days under conditions of relative humidity 75% and 92.5% at 25 DEG C, sampled in the 5th day and the 10th day, to take
Xie Erfa measures the moisture of each sample, and result of the test was compared with 0 day, and experimental result is shown in Table 3.
Table 3 hygroscopicity test results
As can be seen from the above table, ceftibuten crystalline compounds of the present invention are substantially non-hygroscopic under high humidity conditions, and it is in high humidity
Stability under environment is substantially better than the ceftibuten using prior art.
Experimental example 4：Influence factor tests
By trial target and reference substance simulation listing packaging, in 60 DEG C of high temperature, illumination 4500Lx, high humidity（RH90%±5%）Under the conditions of
Place 10 days, detected by stability high spot reviews project, compare with 0 day sample, the results are shown in Table 4.
Table 4 compounds affect factorial experimentss result
The height of drug quality is directly connected to the health of millions upon millions of working people's bodies, is also related to the one-tenth of China's economic construction
Effect, the consolidation of national defence and nationality flourishing；It has been far from the thing of medical industry enterprise scope itself, but the whole people
Race, the major issue in the world.Those skilled in the art all clearly know, in the present age that pharmaceutical technology is flourishing, drug safety standard is not by
Disconnected lifting, the purity also more and more higher of prepared medicine, it is effectively reduced impurity content, even several percentage points of zero point,
The generation of untoward reaction can also be effectively reduced, therefore impurity content is most important to drug quality and people's drug safety.
Medicine needs to store and transport just can cure the sickness to save the patient from production to the process of circulation, therefore, medicine in storage and transportation
Quality is particularly important, and stability is the key determining drug quality quality, in medicine storage and transportation, stability
Bad, impurity change directly affects greatly people's drug safety.
As can be seen from the above table, the relevant material of ceftibuten crystalline compounds of the present invention, polymer equal size are all very low,
And stability is significantly better than the ceftibuten of prior art, effectively improve the stability of drug safety and storage, reduce
The generation of untoward reaction.
Above-mentioned experimental example 1-4 is also carried out to the ceftibuten crystalline compounds of other embodiments of the present invention, it obtains
Result is similar.
Experimental example 6：Compositionss influence factor tests
Formulation test product 1：Ceftibuten pharmaceutical composition prepared by invention formulation embodiment 1.
Formulation test product 2：Ceftibuten pharmaceutical composition prepared by invention formulation embodiment 2.
By formulation test product simulation listing packaging, in 60 DEG C of high temperature, illumination 4500Lx, high humidity（RH90%±5%）Under the conditions of
Place 10 days, detected by stability high spot reviews project, compare with 0 day sample, the results are shown in Table 5.
Table 5 preparation influence factor's result of the test
Found by result above, the pharmaceutical composition purity containing this ceftibuten crystalline compounds prepared by the present invention is high,
Impurity content is low, good stability.
Above-mentioned test is also carried out to the ceftibuten pharmaceutical composition of present invention other example of formulations, its knot obtaining
Really similar.
Claims (1)
1. a kind of medicine ceftibuten crystalline compounds treating Postoperative infection it is characterised in that：Described ceftibuten
The structural formula of crystalline compounds as shown in formula I, this crystalline compounds with powder X-ray diffraction algoscopy measure, with 2 θ ±
X-ray powder diffraction pattern that 0.2 ° of angle of diffraction represents as shown in figure 1,
Formula（）.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610837277.9A CN106432271A (en) | 2016-09-21 | 2016-09-21 | Pharmaceutical ceftibuten crystal compound for treating surgical infection |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610837277.9A CN106432271A (en) | 2016-09-21 | 2016-09-21 | Pharmaceutical ceftibuten crystal compound for treating surgical infection |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023278945A1 (en) * | 2021-07-01 | 2023-01-05 | Qpex Biopharma, Inc. | Crystalline forms of ceftibuten |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87105009A (en) * | 1986-07-02 | 1988-03-23 | 盐野义制药株式会社 | A kind of crystal hydrate of oral cephalosporin and composition thereof |
| WO2013151518A1 (en) * | 2012-04-04 | 2013-10-10 | Mahmut Bilgic | Capsule formulations comprising ceftibuten |
| CN105153198A (en) * | 2015-09-17 | 2015-12-16 | 浙江华方药业股份有限公司 | Preparation method of ceftibuten |
| EP3031450A1 (en) * | 2014-12-12 | 2016-06-15 | Sanovel Ilac Sanayi ve Ticaret A.S. | Ceftibuten capsule compositions |
| WO2016116892A1 (en) * | 2015-01-24 | 2016-07-28 | Wockhardt Limited | Antibacterial compositions |
-
2016
- 2016-09-21 CN CN201610837277.9A patent/CN106432271A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN87105009A (en) * | 1986-07-02 | 1988-03-23 | 盐野义制药株式会社 | A kind of crystal hydrate of oral cephalosporin and composition thereof |
| US4812561A (en) * | 1986-07-02 | 1989-03-14 | Shionogi & Co., Ltd. | Crystalline hydrate of oral cephalosporin and its composition |
| WO2013151518A1 (en) * | 2012-04-04 | 2013-10-10 | Mahmut Bilgic | Capsule formulations comprising ceftibuten |
| EP3031450A1 (en) * | 2014-12-12 | 2016-06-15 | Sanovel Ilac Sanayi ve Ticaret A.S. | Ceftibuten capsule compositions |
| WO2016116892A1 (en) * | 2015-01-24 | 2016-07-28 | Wockhardt Limited | Antibacterial compositions |
| CN105153198A (en) * | 2015-09-17 | 2015-12-16 | 浙江华方药业股份有限公司 | Preparation method of ceftibuten |
Non-Patent Citations (1)
| Title |
|---|
| MITSURU YOSHIOKA: "Synthetic studies related to oral β-lactam antibiotics", 《PURE & APPL. CHEM.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023278945A1 (en) * | 2021-07-01 | 2023-01-05 | Qpex Biopharma, Inc. | Crystalline forms of ceftibuten |
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